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Books by Krishnan Nair

Research paper thumbnail of Preclinical Investigations on antineoplastic activity of Iron oxide Nanoparticle -drug complexes

The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the... more The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the use of iron oxide nanoparticles and a nitro triazole compound, Sanazole which gets accumulated in hypoxic tumor tissue. Under in vitro conditions the nanoparticles complexed with Berberine and Sanazole showed higher cytotoxicity to tumor cells than either of the drugs and complexes of single individual compounds. The tumor-bearing animals treated with these nanoparticle-drug complexes increased the regression in tumor volume and survival of the animals. The present work thus revealed the potential applications of Berberine and Sanazole in cancer therapy.

Research paper thumbnail of Protection of Cellular DNA and Membrane from g-Radiation-Induced Damages and Enhancement in DNA Repair by Sesamol

Sesamol (SM), a nutritional phenolic antioxidant compound present in sesame seeds, protected pBR ... more Sesamol (SM), a nutritional phenolic antioxidant compound present in sesame seeds, protected pBR 322 DNA from gamma radiation-induced damages. SM prevented gamma radiation-induced degradation of covalently closed circular form of plasmid DNA in a concentration-dependent manner. Also SM protected cellular DNA of mouse blood leukocytes exposed to 4 Gy gamma radiation, ex vivo, as revealed by the data from alkaline comet assay studies. SM (5 mM) showed a faster time-dependant decrease of the radiation-induced DNA damage in mouse blood leukocytes following postirradiation incubation ex vivo, which could be attributed to enhanced DNA repair. SM protected the biomembranes from radiation-induced lipid peroxidation. Thus, SM could act as a radioprotector for the biomembranes and cellular DNA against the deleterious effects of ionizing radiation.

Research paper thumbnail of Curcumin VC IJRR 2013 Adi

Ionizing radiation induced cellular damages, such as reproductive death, interphase death, divisi... more Ionizing radiation induced cellular damages, such as reproductive death, interphase death, division delay, chromosome aberrations, mutations etc. are attributed to irreversible changes resulting from the deposition of energy, generating free radicals, reactive oxygen species their accumulation and the subsequent cellular alterations (1). Agents which can prevent the formation of free radicals during radiation or destroy free radicals by reacting with them, thereby inhibiting their reaction with biomolecules, might be considered as radioprotectors (2). The use of dietary antioxidants to prevent antitumor agent-induced chromosomal damage in normal cells is also of considerable interest. The ability of dietary antioxidants to protect cellular DNA from radiation induced and chemical induced damages has been the focus of active research (3) and the present work

Research paper thumbnail of Amelioration of γ-radiation induced genomic insult and oxidative stress in whole body irradiated Swiss albino mice by sesamol

Sesamol (3,4-methylene dioxyphenol) protected mice from adverse effects of whole body gamma-irrad... more Sesamol (3,4-methylene dioxyphenol) protected mice from adverse effects of whole body gamma-irradiation. Studies indicated that oral administration of sesamol (SM), 1 hour prior to whole body gamma-irradiation (2-6 Gy), significantly protected cellular DNA in various tissues of mice, as evident from alkaline comet assay. Whole body exposure of mice to a sublethal dose of 6 Gy gamma radiation resulted in oxidative damage in various tissues of mice, and radiation-induced peroxidative damage and depletion of antioxidants such as GSH, GPx in tissues such as liver, kidney and brain. Administration of SM prior to radiation exposure resulted in prevention of radiation-induced peroxidation of membrane lipids and depletion of cellular antioxidants in these tissues. The administration of SM significantly reduced the mortality of the animals following exposure to a lethal dose of 10 Gy whole body gamma-radiation and improved the recovery of the body weight. Thus the studies suggest that oral administration of SM could offer protection to mice from the deleterious effects of ionising radiation.

Research paper thumbnail of D-Aminoacid Oxidase-Fe 2 O 3 Nanoparticle Complex Mediated Antitumor Activity in Swiss Albino Mice

D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was stu... more D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was studied under in vitro and in vivo conditions. The isolated DAO was complexed with Fe 2 O 3 nanoparticles and its potential as an oxidation therapeutic agent was analysed. The ability of the complex in eliciting H 2 O 2 mediated cytotoxicity was studied on Dalton's lymphoma ascites cells (DLA). The induction of apoptosis in DLA cells by Fe 2 O 3-DAO complex was studied by morphological examination and alkaline single cell gel electrophoresis (comet assay). The antitumor activity of the complex was investigated by oral administration of the complex and the substrate D-alanine to tumor bearing Swiss albino mice and by targeting the complex to the tumor site, using an externally applied magnetic field. Fe 2 O 3-DAO along with D-alanine showed remarkable cytotoxicity in a substrate concentration-dependent manner. Both morphological examination and comet assay revealed that Fe 2 O 3-DAO/D-alanine induced apoptosis. Oral administration of Fe 2 O 3-DAO and D-alanine along with magnetic targeting significantly suppressed tumor growth in mice. The present report provides the first evidence for the promising application of enzyme bound nanoparticles for targeted oxidation therapy.

Research paper thumbnail of Effect of silver nanoparticle and glycyrrhizic acid (SN-GLY) complex on repair of whole body radiation-induced cellular DNA damage and genomic instability in mice

Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed wit... more Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed with the phytoceutical, glycyrrhizic acid (GLY) to obtain SN-GLY complex. The ability of the SN-GLY complex to offer protection against ionising radiation in post-irradiation scenarios was evaluated in ex vivo and in vivo models using Swiss albino mice. Treatment of mouse blood leucocytes with SN-GLY immediately after 4 Gy gamma radiation exposure, ex vivo, enhanced the rate of repair of cellular DNA damages as revealed by comet assay. Exposure of mice to 4 Gy whole body gamma radiation induced formation of strand breaks in cellular DNA and the unrepaired double strand breaks eventually caused the formation of micronuclei. The post-irradiation administration of SN-GLY resulted in a faster decrease in the comet parameters indicating enhanced cellular DNA repair process and reduction in micronucleus formation. Thus the studies showed effective radiation protection by SN-GLY in post-irradiation conditions.

Research paper thumbnail of Effect of silver nanoparticle and glycyrrhizic acid (SN-GLY) complex on repair of whole body radiation-induced cellular DNA damage and genomic instability in mice

Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed wit... more Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed with the phytoceutical, glycyrrhizic acid (GLY) to obtain SN-GLY complex. The ability of the SN-GLY complex to offer protection against ionising radiation in post-irradiation scenarios was evaluated in ex vivo and in vivo models using Swiss albino mice. Treatment of mouse blood leucocytes with SN-GLY immediately after 4 Gy gamma radiation exposure, ex vivo, enhanced the rate of repair of cellular DNA damages as revealed by comet assay. Exposure of mice to 4 Gy whole body gamma radiation induced formation of strand breaks in cellular DNA and the unrepaired double strand breaks eventually caused the formation of micronuclei. The post-irradiation administration of SN-GLY resulted in a faster decrease in the comet parameters indicating enhanced cellular DNA repair process and reduction in micronucleus formation. Thus the studies showed effective radiation protection by SN-GLY in post-irradiation conditions.

Research paper thumbnail of Medicinal fungus Ganoderma lucidum protects cellular DNA in mice exposed to whole-body gamma radiation

Ganoderma lucidum is a medicinal fungus with a variety of biological activities and is used for t... more Ganoderma lucidum is a medicinal fungus with a variety of biological activities and is used for the treatment of various diseases, including cancers. The present work is focused on the radioprotective property of G. lucidum in Swiss albino mice. Whole-body exposure of the mice to gamma radiation results in damage to cellular DNA in various tissues, such as brain, bone marrow, blood and intestine, and prior administration of a hydroalcoholic extract of G. lucidum prevented radiation-induced DNA damage. Administration of the extract prior to whole-body exposure to a lethal dose of gamma radiation gave survival advantage to mice. Also, there was considerable protection from radiation-induced loss of body weight in animals administered with the extract. The results are suggestive of the radioprotective activity of G. lucidum Extract (GLE) in mammalian organism.

Research paper thumbnail of Amelioration of cisplatin-induced nephrotoxicity by extracts of Hemidesmus indicus and Acorus calamus

Administration of commonly used anticancer drug cisplatin [cis-diamminedichloroplatinum (II)] at ... more Administration of commonly used anticancer drug cisplatin [cis-diamminedichloroplatinum (II)] at pharmacologically relevant concentrations (12 mg/kg body weight) resulted in severe renal toxicity as evidenced from histopathological observations and biochemical alterations in the renal tissue. The extracts of medicinal plants Hemidesmus indicus L. (Apocynaceae) and Acorus calamus L. (Araceae) protected the renal tissue effectively from cisplatin-induced toxicity. Treatment of cisplatin-administered animals with the plant extracts could prevent the drug-induced oxidative damage in the renal tissue as evidenced from the decreased levels of lipid peroxidation and enhanced activities of the antioxidants in the renal tissue. Cisplatin treatment increased serum urea level to 41.3 ± 2.86 mg/dL and administration of the extracts of H. indicus and A. calamus brought down the level to 34.54 ± 0.37 and 30.12 ± 0.95 mg/dL, respectively. Serum creatinine levels were increased to 1.1 ± 0.02 mg/dL following cisplatin administration, and treatment with extracts of H. indicus and A. calamus brought this down to 0.76 ± 0.09 and 0.61 ± 0.06 mg/dL, respectively. The histopathological observations indicated that treatment with the H. indicus and A. calamus extracts restored the cisplatin-induced structural alterations in the renal tissue.

Research paper thumbnail of Preclinical Investigations on antineoplastic activity of Iron oxide Nanoparticle -drug complexes

The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the... more The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the use of iron oxide nanoparticles and a nitro triazole compound, Sanazole which gets accumulated in hypoxic tumor tissue. Under in vitro conditions the nanoparticles complexed with Berberine and Sanazole showed higher cytotoxicity to tumor cells than either of the drugs and complexes of single individual compounds. The tumor-bearing animals treated with these nanoparticle-drug complexes increased the regression in tumor volume and survival of the animals. The present work thus revealed the potential applications of Berberine and Sanazole in cancer therapy.

Research paper thumbnail of Ayurvedic formulations ameliorate cisplatin-induced nephrotoxicity: Preclinical studies on Brahma Rasayana and Chyavanaprash

Aim of Study: To explore the ability of two Ayurvedic formulations, Brahma Rasayana (BRM) and Chy... more Aim of Study: To explore the ability of two Ayurvedic formulations, Brahma Rasayana (BRM) and Chyavanaprash (CHM) in alleviating Cisplatin (Cis-dichlorodiammineplatinum [II] CDDP) induced acute nephrotoxicity. Materials and Methods: Swiss albino mice were administered with CDDP (12 mg/kg, i.p) and two doses of BRM or CHM (1 and 2 g/kg). Various antioxidant parameters in the kidney as well as release of marker enzymes in the serum were assayed. Histology of the kidney was also performed to check for CDDP induced damages. Results: Administration of either BRM or CHM (1 and 2 g/kg) maintained the antioxidant status in the kidney thereby preventing tissue damage as well as the release of marker enzymes. CDDP induced variation of renal architecture was also prevented by BRM and CHM administration. Conclusion: BRM and CHM administration could prevent CDDP induced acute renal toxicity.

Research paper thumbnail of Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and a-tocopherol

Background: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatme... more Background: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, is effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals. Methods: Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or atocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue. Results: Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation. Conclusion: These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity.

Research paper thumbnail of SILVER NANOPARTICLE-GALLIC ACID COMPLEX AS AN ADJUVANT IN TUMOUR RADIOTHERAPY: A PRECLINICAL EVALUATION

Gallic acid [3,4,5-trihydroxybenzoic acid, C 6 H 2 (OH) 3 COOH], a phyto-phenolic compound, was u... more Gallic acid [3,4,5-trihydroxybenzoic acid, C 6 H 2 (OH) 3 COOH], a phyto-phenolic compound, was used to reduce silver nitrate to silver nanoparticles. The resultant solution of silver nanoparticles complexed with gallic acid (SN-GA) was analysed for radioprotective and anti-tumor activity under in vitro, ex vivo and in vivo conditions. Comet assay performed, in vivo, to analyze the effect of SN-GA in combination with radiotherapy on the extent of cellular DNA damage showed considerable protection to normal cells while sparing the tumor cells. Biochemical analysis of cellular antioxidant levels in various tissues excised from irradiated tumor bearing animals confirmed the radioprotective property of SN-GA in normal tissues. Thus, the nanoparticle complex of GA offers radiation protection to normal cells by maintaining the cellular antioxidant levels in normal tissues and protecting cellular DNA from radiation induced damage. The study showed the enhanced efficacy of the silver nanoparticle complex of gallic acid when compared to gallic acid alone as a radioprotector and anti-tumor agent in adjuvant-radiotherapy.

Research paper thumbnail of STUDIES ON RADIATION PROTECTION BY SILVER NANOPARTICLE COMPLEXES OF PALMITOYL ASCORBIC ACID 2-GLUCOSIDE

Silver nanoparticles were synthesized from silver nitrate in presence of 6-palmitoyl ascorbic aci... more Silver nanoparticles were synthesized from silver nitrate in presence of 6-palmitoyl ascorbic acid 2-glucoside (PAsAG). PAsAG has various functional groups such as OH and C=O, with long carbon chain which makes it a suitable surfactant for the nanoparticles which is believed to impart reducing character thus making it suitable as a mild reducing agent to noble metal salts i.e. silver nitrate under the impact of ultrasound energy. This antioxidant compound itself reduced silver nitrate to silver nanoparticles, eliminating the need for an additional reducing and/or stabilizing agent. An absorption band in UV-visible spectrum at about 415 nm was indicative of formation of silver nanoparticles in the so formed golden yellow solution. The average size of the particles is less than 5 nm. The silver bonded drug solution (SN-PAsAG) was analyzed for the radioprotecting ability under in vitro, ex vivo and in vivo models on murine system and it was found that the complex possess increased protecting ability compared to the corresponding antioxidant compound, PAsAG. The enhanced protection might be due to the additive free radical scavenging property of the constituent components, PAsAG and silver nanoparticles, present in the complex.

Research paper thumbnail of Mitigating Acetaminophen-Induced Hepatotoxicity by Using a Water-Alcohol Extract of Phellinus caryophylli (Agaricomycetes) in a Murine Model

This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal m... more This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.

Research paper thumbnail of Synthesis of Silver Nanoparticles Using Cod Liver Oil (Fish Oil): Green Approach to Nanotechnology

and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.

Research paper thumbnail of Protection of DNA from gamma-radiation induced strand breaks by Epicatechin

Epicatechin (EC), a polyphenolic antioxidant compound found in tea, apples and chocolate offered ... more Epicatechin (EC), a polyphenolic antioxidant compound found in tea, apples and chocolate offered protection to DNA against ionizing radiation induced damages. Under in vitro conditions of radiation exposure, plasmid pBR322 DNA was protected by EC in a concentration dependent manner. The dose modifying factor for 0.2 mM EC for 50% protection of the plasmid DNA was found to be 6.0. EC when administered to mice 1 h prior to exposure to 4 Gy gamma-radiation protected cellular DNA against radiation-induced strand breaks in peripheral blood leukocytes, as revealed in alkaline comet assay studies. Thus, EC was found to protect DNA from gamma-radiation indiced strand breaks under in vitro as well as in vivo conditions of radiation exposure.

Research paper thumbnail of Mutation Research/Genetic Toxicology and Environmental Mutagenesis

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:

Research paper thumbnail of Preparation and preliminary biological evaluation of a 177 Lu labeled sanazole derivative for possible use in targeting tumor hypoxia

The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therap... more The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therapeutic radioisotope viz. 177 Lu is described. The nitroimidazole used for the present study is [N-2 0 (carboxyethyl)-2-(3 0-nitro-1 0-triazolyl)acetamide], the carboxylic acid derivative of sanazole, which possesses an optimal combination of desired properties such as, selective toxicity for hypoxic cells, lowered lipophilicity resulting in lowered neurotoxicity. The bifunctional chelating agent is a DOTA derivative viz. 1,4,7,10-tetraaza-1-(4 0-aminobenzylacetamido)-cyclododecane-4,7,10-triacetic acid (p-amino-DOTA-anilide). 177 Lu was produced in adequate specific activity (110 TBq/g) and high radionuclidic purity ($100%) by irradiating enriched (60.6% 176 Lu) Lu 2 O 3 target and used for radiolabeling of the sanazole-BFCA conjugate. $98% Complexation yield was achieved under optimized conditions. The complex has been characterized by paper chromatography and HPLC studies. Bioevaluation studies in Swiss mice bearing fibrosarcoma tumors revealed moderate tumor uptake (0.88%/g at 1 h post-injection) with favorable tumor to blood (4.00 at 1 h post-injection) and tumor to muscle (4.63 at 1 h post-injection) ratios.

Research paper thumbnail of Mutation Research/Genetic Toxicology and Environmental Mutagenesis

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:

Research paper thumbnail of Preclinical Investigations on antineoplastic activity of Iron oxide Nanoparticle -drug complexes

The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the... more The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the use of iron oxide nanoparticles and a nitro triazole compound, Sanazole which gets accumulated in hypoxic tumor tissue. Under in vitro conditions the nanoparticles complexed with Berberine and Sanazole showed higher cytotoxicity to tumor cells than either of the drugs and complexes of single individual compounds. The tumor-bearing animals treated with these nanoparticle-drug complexes increased the regression in tumor volume and survival of the animals. The present work thus revealed the potential applications of Berberine and Sanazole in cancer therapy.

Research paper thumbnail of Protection of Cellular DNA and Membrane from g-Radiation-Induced Damages and Enhancement in DNA Repair by Sesamol

Sesamol (SM), a nutritional phenolic antioxidant compound present in sesame seeds, protected pBR ... more Sesamol (SM), a nutritional phenolic antioxidant compound present in sesame seeds, protected pBR 322 DNA from gamma radiation-induced damages. SM prevented gamma radiation-induced degradation of covalently closed circular form of plasmid DNA in a concentration-dependent manner. Also SM protected cellular DNA of mouse blood leukocytes exposed to 4 Gy gamma radiation, ex vivo, as revealed by the data from alkaline comet assay studies. SM (5 mM) showed a faster time-dependant decrease of the radiation-induced DNA damage in mouse blood leukocytes following postirradiation incubation ex vivo, which could be attributed to enhanced DNA repair. SM protected the biomembranes from radiation-induced lipid peroxidation. Thus, SM could act as a radioprotector for the biomembranes and cellular DNA against the deleterious effects of ionizing radiation.

Research paper thumbnail of Curcumin VC IJRR 2013 Adi

Ionizing radiation induced cellular damages, such as reproductive death, interphase death, divisi... more Ionizing radiation induced cellular damages, such as reproductive death, interphase death, division delay, chromosome aberrations, mutations etc. are attributed to irreversible changes resulting from the deposition of energy, generating free radicals, reactive oxygen species their accumulation and the subsequent cellular alterations (1). Agents which can prevent the formation of free radicals during radiation or destroy free radicals by reacting with them, thereby inhibiting their reaction with biomolecules, might be considered as radioprotectors (2). The use of dietary antioxidants to prevent antitumor agent-induced chromosomal damage in normal cells is also of considerable interest. The ability of dietary antioxidants to protect cellular DNA from radiation induced and chemical induced damages has been the focus of active research (3) and the present work

Research paper thumbnail of Amelioration of γ-radiation induced genomic insult and oxidative stress in whole body irradiated Swiss albino mice by sesamol

Sesamol (3,4-methylene dioxyphenol) protected mice from adverse effects of whole body gamma-irrad... more Sesamol (3,4-methylene dioxyphenol) protected mice from adverse effects of whole body gamma-irradiation. Studies indicated that oral administration of sesamol (SM), 1 hour prior to whole body gamma-irradiation (2-6 Gy), significantly protected cellular DNA in various tissues of mice, as evident from alkaline comet assay. Whole body exposure of mice to a sublethal dose of 6 Gy gamma radiation resulted in oxidative damage in various tissues of mice, and radiation-induced peroxidative damage and depletion of antioxidants such as GSH, GPx in tissues such as liver, kidney and brain. Administration of SM prior to radiation exposure resulted in prevention of radiation-induced peroxidation of membrane lipids and depletion of cellular antioxidants in these tissues. The administration of SM significantly reduced the mortality of the animals following exposure to a lethal dose of 10 Gy whole body gamma-radiation and improved the recovery of the body weight. Thus the studies suggest that oral administration of SM could offer protection to mice from the deleterious effects of ionising radiation.

Research paper thumbnail of D-Aminoacid Oxidase-Fe 2 O 3 Nanoparticle Complex Mediated Antitumor Activity in Swiss Albino Mice

D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was stu... more D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was studied under in vitro and in vivo conditions. The isolated DAO was complexed with Fe 2 O 3 nanoparticles and its potential as an oxidation therapeutic agent was analysed. The ability of the complex in eliciting H 2 O 2 mediated cytotoxicity was studied on Dalton's lymphoma ascites cells (DLA). The induction of apoptosis in DLA cells by Fe 2 O 3-DAO complex was studied by morphological examination and alkaline single cell gel electrophoresis (comet assay). The antitumor activity of the complex was investigated by oral administration of the complex and the substrate D-alanine to tumor bearing Swiss albino mice and by targeting the complex to the tumor site, using an externally applied magnetic field. Fe 2 O 3-DAO along with D-alanine showed remarkable cytotoxicity in a substrate concentration-dependent manner. Both morphological examination and comet assay revealed that Fe 2 O 3-DAO/D-alanine induced apoptosis. Oral administration of Fe 2 O 3-DAO and D-alanine along with magnetic targeting significantly suppressed tumor growth in mice. The present report provides the first evidence for the promising application of enzyme bound nanoparticles for targeted oxidation therapy.

Research paper thumbnail of Effect of silver nanoparticle and glycyrrhizic acid (SN-GLY) complex on repair of whole body radiation-induced cellular DNA damage and genomic instability in mice

Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed wit... more Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed with the phytoceutical, glycyrrhizic acid (GLY) to obtain SN-GLY complex. The ability of the SN-GLY complex to offer protection against ionising radiation in post-irradiation scenarios was evaluated in ex vivo and in vivo models using Swiss albino mice. Treatment of mouse blood leucocytes with SN-GLY immediately after 4 Gy gamma radiation exposure, ex vivo, enhanced the rate of repair of cellular DNA damages as revealed by comet assay. Exposure of mice to 4 Gy whole body gamma radiation induced formation of strand breaks in cellular DNA and the unrepaired double strand breaks eventually caused the formation of micronuclei. The post-irradiation administration of SN-GLY resulted in a faster decrease in the comet parameters indicating enhanced cellular DNA repair process and reduction in micronucleus formation. Thus the studies showed effective radiation protection by SN-GLY in post-irradiation conditions.

Research paper thumbnail of Effect of silver nanoparticle and glycyrrhizic acid (SN-GLY) complex on repair of whole body radiation-induced cellular DNA damage and genomic instability in mice

Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed wit... more Silver nanoparticles (SN) were redispersed in aqueous solution of Pluronic F127 and complexed with the phytoceutical, glycyrrhizic acid (GLY) to obtain SN-GLY complex. The ability of the SN-GLY complex to offer protection against ionising radiation in post-irradiation scenarios was evaluated in ex vivo and in vivo models using Swiss albino mice. Treatment of mouse blood leucocytes with SN-GLY immediately after 4 Gy gamma radiation exposure, ex vivo, enhanced the rate of repair of cellular DNA damages as revealed by comet assay. Exposure of mice to 4 Gy whole body gamma radiation induced formation of strand breaks in cellular DNA and the unrepaired double strand breaks eventually caused the formation of micronuclei. The post-irradiation administration of SN-GLY resulted in a faster decrease in the comet parameters indicating enhanced cellular DNA repair process and reduction in micronucleus formation. Thus the studies showed effective radiation protection by SN-GLY in post-irradiation conditions.

Research paper thumbnail of Medicinal fungus Ganoderma lucidum protects cellular DNA in mice exposed to whole-body gamma radiation

Ganoderma lucidum is a medicinal fungus with a variety of biological activities and is used for t... more Ganoderma lucidum is a medicinal fungus with a variety of biological activities and is used for the treatment of various diseases, including cancers. The present work is focused on the radioprotective property of G. lucidum in Swiss albino mice. Whole-body exposure of the mice to gamma radiation results in damage to cellular DNA in various tissues, such as brain, bone marrow, blood and intestine, and prior administration of a hydroalcoholic extract of G. lucidum prevented radiation-induced DNA damage. Administration of the extract prior to whole-body exposure to a lethal dose of gamma radiation gave survival advantage to mice. Also, there was considerable protection from radiation-induced loss of body weight in animals administered with the extract. The results are suggestive of the radioprotective activity of G. lucidum Extract (GLE) in mammalian organism.

Research paper thumbnail of Amelioration of cisplatin-induced nephrotoxicity by extracts of Hemidesmus indicus and Acorus calamus

Administration of commonly used anticancer drug cisplatin [cis-diamminedichloroplatinum (II)] at ... more Administration of commonly used anticancer drug cisplatin [cis-diamminedichloroplatinum (II)] at pharmacologically relevant concentrations (12 mg/kg body weight) resulted in severe renal toxicity as evidenced from histopathological observations and biochemical alterations in the renal tissue. The extracts of medicinal plants Hemidesmus indicus L. (Apocynaceae) and Acorus calamus L. (Araceae) protected the renal tissue effectively from cisplatin-induced toxicity. Treatment of cisplatin-administered animals with the plant extracts could prevent the drug-induced oxidative damage in the renal tissue as evidenced from the decreased levels of lipid peroxidation and enhanced activities of the antioxidants in the renal tissue. Cisplatin treatment increased serum urea level to 41.3 ± 2.86 mg/dL and administration of the extracts of H. indicus and A. calamus brought down the level to 34.54 ± 0.37 and 30.12 ± 0.95 mg/dL, respectively. Serum creatinine levels were increased to 1.1 ± 0.02 mg/dL following cisplatin administration, and treatment with extracts of H. indicus and A. calamus brought this down to 0.76 ± 0.09 and 0.61 ± 0.06 mg/dL, respectively. The histopathological observations indicated that treatment with the H. indicus and A. calamus extracts restored the cisplatin-induced structural alterations in the renal tissue.

Research paper thumbnail of Preclinical Investigations on antineoplastic activity of Iron oxide Nanoparticle -drug complexes

The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the... more The present study aims to target a cytotoxic drug, Berberine to tumor tissues specifically by the use of iron oxide nanoparticles and a nitro triazole compound, Sanazole which gets accumulated in hypoxic tumor tissue. Under in vitro conditions the nanoparticles complexed with Berberine and Sanazole showed higher cytotoxicity to tumor cells than either of the drugs and complexes of single individual compounds. The tumor-bearing animals treated with these nanoparticle-drug complexes increased the regression in tumor volume and survival of the animals. The present work thus revealed the potential applications of Berberine and Sanazole in cancer therapy.

Research paper thumbnail of Ayurvedic formulations ameliorate cisplatin-induced nephrotoxicity: Preclinical studies on Brahma Rasayana and Chyavanaprash

Aim of Study: To explore the ability of two Ayurvedic formulations, Brahma Rasayana (BRM) and Chy... more Aim of Study: To explore the ability of two Ayurvedic formulations, Brahma Rasayana (BRM) and Chyavanaprash (CHM) in alleviating Cisplatin (Cis-dichlorodiammineplatinum [II] CDDP) induced acute nephrotoxicity. Materials and Methods: Swiss albino mice were administered with CDDP (12 mg/kg, i.p) and two doses of BRM or CHM (1 and 2 g/kg). Various antioxidant parameters in the kidney as well as release of marker enzymes in the serum were assayed. Histology of the kidney was also performed to check for CDDP induced damages. Results: Administration of either BRM or CHM (1 and 2 g/kg) maintained the antioxidant status in the kidney thereby preventing tissue damage as well as the release of marker enzymes. CDDP induced variation of renal architecture was also prevented by BRM and CHM administration. Conclusion: BRM and CHM administration could prevent CDDP induced acute renal toxicity.

Research paper thumbnail of Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and a-tocopherol

Background: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatme... more Background: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, is effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals. Methods: Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or atocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue. Results: Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation. Conclusion: These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity.

Research paper thumbnail of SILVER NANOPARTICLE-GALLIC ACID COMPLEX AS AN ADJUVANT IN TUMOUR RADIOTHERAPY: A PRECLINICAL EVALUATION

Gallic acid [3,4,5-trihydroxybenzoic acid, C 6 H 2 (OH) 3 COOH], a phyto-phenolic compound, was u... more Gallic acid [3,4,5-trihydroxybenzoic acid, C 6 H 2 (OH) 3 COOH], a phyto-phenolic compound, was used to reduce silver nitrate to silver nanoparticles. The resultant solution of silver nanoparticles complexed with gallic acid (SN-GA) was analysed for radioprotective and anti-tumor activity under in vitro, ex vivo and in vivo conditions. Comet assay performed, in vivo, to analyze the effect of SN-GA in combination with radiotherapy on the extent of cellular DNA damage showed considerable protection to normal cells while sparing the tumor cells. Biochemical analysis of cellular antioxidant levels in various tissues excised from irradiated tumor bearing animals confirmed the radioprotective property of SN-GA in normal tissues. Thus, the nanoparticle complex of GA offers radiation protection to normal cells by maintaining the cellular antioxidant levels in normal tissues and protecting cellular DNA from radiation induced damage. The study showed the enhanced efficacy of the silver nanoparticle complex of gallic acid when compared to gallic acid alone as a radioprotector and anti-tumor agent in adjuvant-radiotherapy.

Research paper thumbnail of STUDIES ON RADIATION PROTECTION BY SILVER NANOPARTICLE COMPLEXES OF PALMITOYL ASCORBIC ACID 2-GLUCOSIDE

Silver nanoparticles were synthesized from silver nitrate in presence of 6-palmitoyl ascorbic aci... more Silver nanoparticles were synthesized from silver nitrate in presence of 6-palmitoyl ascorbic acid 2-glucoside (PAsAG). PAsAG has various functional groups such as OH and C=O, with long carbon chain which makes it a suitable surfactant for the nanoparticles which is believed to impart reducing character thus making it suitable as a mild reducing agent to noble metal salts i.e. silver nitrate under the impact of ultrasound energy. This antioxidant compound itself reduced silver nitrate to silver nanoparticles, eliminating the need for an additional reducing and/or stabilizing agent. An absorption band in UV-visible spectrum at about 415 nm was indicative of formation of silver nanoparticles in the so formed golden yellow solution. The average size of the particles is less than 5 nm. The silver bonded drug solution (SN-PAsAG) was analyzed for the radioprotecting ability under in vitro, ex vivo and in vivo models on murine system and it was found that the complex possess increased protecting ability compared to the corresponding antioxidant compound, PAsAG. The enhanced protection might be due to the additive free radical scavenging property of the constituent components, PAsAG and silver nanoparticles, present in the complex.

Research paper thumbnail of Mitigating Acetaminophen-Induced Hepatotoxicity by Using a Water-Alcohol Extract of Phellinus caryophylli (Agaricomycetes) in a Murine Model

This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal m... more This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.

Research paper thumbnail of Synthesis of Silver Nanoparticles Using Cod Liver Oil (Fish Oil): Green Approach to Nanotechnology

and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.

Research paper thumbnail of Protection of DNA from gamma-radiation induced strand breaks by Epicatechin

Epicatechin (EC), a polyphenolic antioxidant compound found in tea, apples and chocolate offered ... more Epicatechin (EC), a polyphenolic antioxidant compound found in tea, apples and chocolate offered protection to DNA against ionizing radiation induced damages. Under in vitro conditions of radiation exposure, plasmid pBR322 DNA was protected by EC in a concentration dependent manner. The dose modifying factor for 0.2 mM EC for 50% protection of the plasmid DNA was found to be 6.0. EC when administered to mice 1 h prior to exposure to 4 Gy gamma-radiation protected cellular DNA against radiation-induced strand breaks in peripheral blood leukocytes, as revealed in alkaline comet assay studies. Thus, EC was found to protect DNA from gamma-radiation indiced strand breaks under in vitro as well as in vivo conditions of radiation exposure.

Research paper thumbnail of Mutation Research/Genetic Toxicology and Environmental Mutagenesis

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:

Research paper thumbnail of Preparation and preliminary biological evaluation of a 177 Lu labeled sanazole derivative for possible use in targeting tumor hypoxia

The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therap... more The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therapeutic radioisotope viz. 177 Lu is described. The nitroimidazole used for the present study is [N-2 0 (carboxyethyl)-2-(3 0-nitro-1 0-triazolyl)acetamide], the carboxylic acid derivative of sanazole, which possesses an optimal combination of desired properties such as, selective toxicity for hypoxic cells, lowered lipophilicity resulting in lowered neurotoxicity. The bifunctional chelating agent is a DOTA derivative viz. 1,4,7,10-tetraaza-1-(4 0-aminobenzylacetamido)-cyclododecane-4,7,10-triacetic acid (p-amino-DOTA-anilide). 177 Lu was produced in adequate specific activity (110 TBq/g) and high radionuclidic purity ($100%) by irradiating enriched (60.6% 176 Lu) Lu 2 O 3 target and used for radiolabeling of the sanazole-BFCA conjugate. $98% Complexation yield was achieved under optimized conditions. The complex has been characterized by paper chromatography and HPLC studies. Bioevaluation studies in Swiss mice bearing fibrosarcoma tumors revealed moderate tumor uptake (0.88%/g at 1 h post-injection) with favorable tumor to blood (4.00 at 1 h post-injection) and tumor to muscle (4.63 at 1 h post-injection) ratios.

Research paper thumbnail of Mutation Research/Genetic Toxicology and Environmental Mutagenesis

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:

Research paper thumbnail of Control of vegf Expression and Tumor Angiogenesis by Nanoparticle-Berberine-Sanazole Complexes

Background: Growth of tumor is fully dependent on angiogenesis for the supply of nutrients which ... more Background: Growth of tumor is fully dependent on angiogenesis for the supply of nutrients which is essential for its proliferation and metastasis. Of the various pro-angiogenic factors,Vascular Endothelial Growth Factor (VEGF) plays a crucial role in the process. Tumor-induced angiogenesis was the key therapeutic target in the present study. The iron oxide nanoparticle-berberine-sanazole (NP-BBN-SAN) complexes were used to control the transcriptional level expression of vegf and thereby prevent neovascularization in animals bearing tumor in the peritoneal cavity. Results: The administration of NP-BBN-SAN complexes inhibited angiogenesis in mice-bearing tumor in the peritoneal cavity. The images of inner peritoneal membrane presented visual differences of angiogenesis in the animals treated with the complexes. At the transcription level the expression of the gene, vegf was found significantly down regulated in the tumor cells following the treatment with NP-BBN-SAN. The order of dow...

Research paper thumbnail of White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents

World Academy of Science, Engineering and Technology, International Journal of Bioengineering and Life Sciences, 2017

Research paper thumbnail of Mitigation of Acetaminophen (APAP) Induced Hepatotoxicity Using Water–Alcohol Extract of Phellinus caryophylli (Agaricomycetes) in Murine Model

International Journal of Medicinal Mushrooms, 2019

This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal m... more This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.

Research paper thumbnail of Reduction of Gamma Radiation Induced Damages by Hydro-Alcoholic Extract of Nardostachys Jatamansi

Journal of Environmental Pathology, Toxicology and Oncology, 2019

The search for a nontoxic radioprotector has not yielded any promising results. Many antioxidant ... more The search for a nontoxic radioprotector has not yielded any promising results. Many antioxidant compounds, though effective under in vitro conditions as radioprotectors, have failed under in vivo settings due to their toxicity. The Indian medical system of Ayurveda uses a variety of plants with antioxidant potential, and these may be harboring molecules with radioprotective properties. In the present work, the radioprotective property of Nardostachys jatamansi was investigated. A hydro-alcoholic extract of this plant provided protection to the cellular DNA and membrane from 4 Gy gamma radiation. Depletion of cellular antioxidant status was also prevented by this extract. Molecular-level analysis in the intestines of mice revealed a lower bax/bcl2 ratio suggestive of a reduction of radiation-induced apoptosis. Expression levels of the DNA repair gene atm were elevated, along with a reduction in the expression of the inflammatory gene cox2. The extract also provided a survival advantage to mice exposed to lethal doses of gamma radiation. These results suggest a possible radioprotective role for Nardostachys jatamansi.

Research paper thumbnail of D-Aminoacid Oxidase-Fe<sub>2</sub>O<sub>3</sub> Nanoparticle Complex Mediated Antitumor Activity in Swiss Albino Mice

Journal of Cancer Therapy, 2011

D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was stu... more D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was studied under in vitro and in vivo conditions. The isolated DAO was complexed with Fe 2 O 3 nanoparticles and its potential as an oxidation therapeutic agent was analysed. The ability of the complex in eliciting H 2 O 2 mediated cytotoxicity was studied on Dalton's lymphoma ascites cells (DLA). The induction of apoptosis in DLA cells by Fe 2 O 3-DAO complex was studied by morphological examination and alkaline single cell gel electrophoresis (comet assay). The antitumor activity of the complex was investigated by oral administration of the complex and the substrate D-alanine to tumor bearing Swiss albino mice and by targeting the complex to the tumor site, using an externally applied magnetic field. Fe 2 O 3-DAO along with D-alanine showed remarkable cytotoxicity in a substrate concentration-dependent manner. Both morphological examination and comet assay revealed that Fe 2 O 3-DAO/D-alanine induced apoptosis. Oral administration of Fe 2 O 3-DAO and D-alanine along with magnetic targeting significantly suppressed tumor growth in mice. The present report provides the first evidence for the promising application of enzyme bound nanoparticles for targeted oxidation therapy.

Research paper thumbnail of Genetic alterations in the coding region of the bak gene in uterine cervical carcinoma

British Journal of Cancer, 2003

A significant frequency of mutations (six missense and one silent) was found, for the first time,... more A significant frequency of mutations (six missense and one silent) was found, for the first time, at the coding region of the bak gene (exons 3, 4 and 6) in 42 carcinomas of the uterine cervix, while no mutations were detected in 32 non-neoplastic cervix tissues. Bak mutations were observed more frequently in the advanced stage and mutated cancer tissues were more resistant to radiotherapy, although trends were not statistically significant because of small sample size.

Research paper thumbnail of One-electron redox reactions of troxerutin in aqueous solutions

Research on Chemical Intermediates, 2005

The oxidation of flavonoids is of great interest because of their action as antioxidants with the... more The oxidation of flavonoids is of great interest because of their action as antioxidants with the ability to scavenge radicals by means of electron-transfer processes. The redox reactions of the flavonoid derivative troxerutin, (2-[3,4-bis-(2-hydroxyethoxy) phenyl]-3[[6-deoxy-α-L-mannopyranosyl)-β-(D-glucopyranosyl]-oxy]-5-hydroxy-7-(2-hydroxyethoxy)-4H-1-benzo-pyran-4-one), were investigated over a wide range of conditions, using pulse radiolysis and cyclic voltammetry. The oxidation mechanism proceeds in sequential steps. One-electron redox potentials for troxerutin were found to be +1.196, +0.846 and −0.634 V vs. NHE.

Research paper thumbnail of Effect of Hypoxic Cell Sensitizer on Transcription of hif-1α and its Target Genes in Tumor Cells

International Journal of Cancer Research, 2016

Hypoxia-selective tumor therapy has great importance since hypoxic environment makes the tumors r... more Hypoxia-selective tumor therapy has great importance since hypoxic environment makes the tumors refractory to radiation and antineoplastic agents. The compounds with hypoxic cell sensitizing property have been evaluated in association with various therapeutic strategies and some of them are found to be operational. Sanazole (a nitrotriazole compound), a well-known hypoxic radiation sensitizer, has been attested for its hypoxiaselective activity at molecular level. In the present study, we have investigated the effect of Sanazole on transcription of major genes responsible for hypoxia-associated tumor growth, such ashif-1α, vegf and egfr, in tumor cells under in vitro and in vivo conditions. The transcriptional expressions of these genes were studied by quantitative real time PCR. The levels of nitric oxide in the tumor cells and tissues were studied by Griess test. The transcription of these geneswere up-regulated in hypoxic tumor cells while it was down regulated significantly in these cells treated with Sanazole compared to the control (normoxic) cells. The same pattern of expression was observed in tumor tissues of animals treated with Sanazole. Thus, the study revealed the effect of Sanazole in hypoxiainduced tumor growth which makes this compound useful for targeting cytotoxic drugs to hypoxic solid tumor.

Research paper thumbnail of Mitigation of whole-body gamma radiation–induced damages by Clerodendron infortunatum in mammalian organisms

Journal of Radiation Research, 2016

Several phytoceuticals and extracts of medicinal plants are reported to mitigate deleterious effe... more Several phytoceuticals and extracts of medicinal plants are reported to mitigate deleterious effects of ionizing radiation. The potential of hydro-alcoholic extract of Clerodendron infortunatum (CIE) for providing protection to mice exposed to gamma radiation was investigated. Oral administration of CIE bestowed a survival advantage to mice exposed to lethal doses of gamma radiation. Radiation-induced depletion of the total blood count and bone marrow cellularity were prevented by treatment with CIE. Damage to the cellular DNA (as was evident from the comet assay and the micronucleus index) was also found to be decreased upon CIE administration. Radiation-induced damages to intestinal crypt cells was also reduced by CIE. Studies on gene expression in intestinal cells revealed that there was a marked increase in the Bax/Bcl-2 ratio in mice exposed to whole-body 4 Gy gamma radiation, and that administration of CIE resulted in significant lowering of this ratio, suggestive of reduction...

Research paper thumbnail of Protective effect of ayurvedic formulations against doxorubicin-induced cardiotoxicity: Preliminary studies on Brahma Rasayana and Chyavanaprash

Journal of Cancer Research and Therapeutics, 2016

The present work aimed to examine the efficacy of two ayurvedic formulations, Brahma Rasayana (BR... more The present work aimed to examine the efficacy of two ayurvedic formulations, Brahma Rasayana (BRM) and Chyavanaprash (CHM) to alleviate doxorubicin (DOX) induced acute cardiotoxicity. Swiss albino mice were administered with DOX (25 mg/kg, i.p.) and two doses of BRM or CHM (1 and 2 g/kg). Cardiotoxicity was assessed by measuring the levels of various antioxidant parameters in the heart as well as release of marker enzymes in the serum was assayed. Histology of the heart was also performed to check for DOX-induced damages. Administration of either BRM or CHM (1 and 2 g/kg) maintained the antioxidant status in the heart thereby preventing tissue damage as well as the release of marker enzymes. DOX-induced variation of cardiac architecture was also prevented by BRM and CHM administration. BRM and CHM administration could prevent DOX-induced acute cardiotoxicity.

Research paper thumbnail of Protection of DNA from Radiation by the Medicinal Plant Holarrhena antidysentrica

Advanced Journal of Phytomedicine and Clinical Therapeutics, Apr 23, 2015

Objective: To investigate the radioprotecting ability of the extract of the medicinal plant Holar... more Objective: To investigate the radioprotecting ability of the extract of the medicinal plant Holarrhena antidysentrica, especially to protect DNA from gamma- radiation induced damages . Materials and Methods: Hydo-alcoholic extract of dried roots of Holarrhena antidysentrica (HAE) was prepared, freeze dried and stored at 4 0 C . The DNA of the plasmid pBR 322 was exposed to gamma-radiation in presence and absence of HAE and subjected to agarose gel electrophoresis to study radioprotecting ability of the extract under in vitro conditions. The radioprotecting ability of the extract under ex-vivo conditions was examined by performing alkaline comet assay on human peripheral blood leucocytes exposed to the radiation with and without HAE. Mice were whole body exposed to gamma- radiation and single cell suspensions of spleen and bone marrow were subjected to alkaline comet assay to investigate the radioprotecting ability of HAE under in vivo conditions. The effect of HAE on radiation induced mortality was checked by monitoring the mortality of mice exposed to 10 Gray(Gy) whole body gamma-radiation after administering HAE. Results: Exposure to gamma-radiation led to induction of DNA strand breaks, resulting in the relaxation of plasmid DNA from super coiled (ccc) form to open circle (oc) form and the presence of HAE during radiation exposure protected the DNA from the induction of strand breaks. The exposure of the human leucocytes to the radiation ex vivo resulted in the increase in the damage to cellular DNA measured as increase in the comet parameters such as percent DNA in tail, tail length and tail moment and olive tail moment and the presence of the extract during irradiation decreased all the comet parameters indicating ex vivo radioprotection of DNA. In whole body irradiated mice cellular DNA damage in bone marrow and spleen cells, seen as increased comet parameters were found reduced by administration of HAE prior to radiation exposure, indicating in vivo radioprotection of DNA. Investigations on survival of animals following acute lethal dose of 10 Gy whole body gamma- radiation showed that the administration of HA provided only a small extent of radioprotection and survival advantage. Conclusions: The results indicate that under in vitro , ex vivo and in vivo conditions of radiation exposure, the extract HAE protects cellular DNA from deleterious effects of radiation and hence it may be useful to prevent genomic insults from radiation.

Research paper thumbnail of Radioprotection by a-Lipoic Acid Palladium Complex Formulation (POLY-MVA) in Mice

Cancer Biother Radiopharm, 2010

Research paper thumbnail of Synthesis of Silver Nanoparticles Using Cod Liver Oil (Fish Oil): Green Approach to Nanotechnology

International Journal of Green Nanotechnology: Physics and Chemistry, 2009

Because cod liver oil is a nutritional supplement and has medicinal value, the presence of permis... more Because cod liver oil is a nutritional supplement and has medicinal value, the presence of permissible limit of silver nanoparticles may enhance its efficacy-an idea that might open many avenues in the field of nanobiotechnology. Keeping the above in mind, the reaction between silver salts and cod liver oil for the synthesis of silver nanoparticles is described herein. Presence of carboxylate ions and amine groups in fish oil facilitates in an in situ generation of organically capped silver nanoparticles. Surface plasmon resonance (SPR) at ∼433-436 nm from the reaction of silver nitrate can be altered to about 484 nm by the use of silver myristate. Broadened x-ray diffraction (XRD) pattern, which is indicative of small particles, confirms the fcc crystal structure of silver. Transmission electron microscope (TEM) analysis shows spherical particle in the range of about 5-10 nm. The present method highlights a environmentally friendly green approach for synthesis with the dual role of cod liver oil, i.e., of a reducing agent as well as that of a surfactant.

Research paper thumbnail of Preliminary biocompatibility assessment of Polylactide membrane intended for wound healing

Research paper thumbnail of Preclinical studies on the use of medicinal mushroom Ganoderma lucidum as an adjuvant in radiotherapy of cancer

Our previous studies have demonstrated that an extract of Ganoderma lucidum occurring in South In... more Our previous studies have demonstrated that an extract of Ganoderma lucidum occurring in South India possesses significant radioprotective property ex vivo. The present study describes the in vivo radiopro-tection of normal cells in tumour-bearing mice exposed to gamma radiation. Oral administration of G. lucidum extract (GLE) to tumour-bearing Swiss albino mice along with exposure to gamma radiation resulted in tumour regression. Single-cell gel electro-phoresis (comet assay) on cells of normal and tumour tissues from tumour-bearing animals treated with GLE and radiation, revealed that there was significant reduction in radiation-induced damage to cellular DNA in normal tissues compared to the tumour, indi-cating preferential protection to normal tissues. The findings suggest the potential use of this mushroom extract as an adjuvant in radiotherapy, for tumour regression and prevention of radiation-induced cellu-lar damages in normal tissues. IONIZING radiation is one of the well-e...

Research paper thumbnail of BIORES.2012.0278

Research paper thumbnail of Targeted drug delivery to tumour using magnetic nanoparticles: Preclinical studies with Fe3O4 – doxorubicin nanoparticles

Research paper thumbnail of Complexes of gold nanoparticle with Sesamol and Glycyrrhizic acid: Studies in vitro on antioxidant activity and radioprotection

Research paper thumbnail of Protection from hemopoetic damage by silver nanoparticle-glycyrrhizic acid complex in mice exposed to whole body gamma-radiation

Research paper thumbnail of Targeted drug delivery to tumour using Fe3O4 nanoparticles: Preclinical studies