Rakesh Johri - Academia.edu (original) (raw)

Papers by Rakesh Johri

Indian journal of experimental biology, 2007

Efficacy of a herbal product of E. officinalis (fruit) (EO) has been evaluated against carbon tet... more Efficacy of a herbal product of E. officinalis (fruit) (EO) has been evaluated against carbon tetrachloride (CCl4) and thioacetamide (TAA) induced changes in rat liver. Chronic treatment of CCl4 and TAA revealed abnormal histopathology indicative of pre-fibrogenic events. EO reversed such alterations with significant regenerative changes suggestive of its preventive role in prefibrogenesis of liver.

Traditional Herbal Medicines for Modern Times, 2011

World journal of gastroenterology : WJG, Jan 21, 2008

To evaluate the protective effect of 2'-p-hydroxybenzoylmussaenosidic acid [negundoside (NG),... more To evaluate the protective effect of 2'-p-hydroxybenzoylmussaenosidic acid [negundoside (NG), against carbon tetrachloride (CCl(4))-induced toxicity in HuH-7 cells. CCl(4) is a well characterized hepatotoxin, and inducer of cytochrome P450 2E1 (CYP2E1)-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl(4) toxicity. Liver cells (HuH-7) were treated with CCl(4), and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control. NG protected HuH-7 cells against CCl(4) toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl(4) toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species (ROS), a decrease in lipid peroxidation and accumulation of intracellular Ca(2+) levels and maintenance of intracellular glutathione homeostasis. ...

International Journal of Life Sciences, 2012

Cancer medically known as malignant neoplasm is a group of different diseases all involving unreg... more Cancer medically known as malignant neoplasm is a group of different diseases all involving unregulated cell growth due to defects in the genetic makeup of two types of genes, i.e. oncogene, which drive the growth of cancer cells and tumor suppressor genes which prevent cancer from developing. Cancer is detected in a number of ways, including symptoms, screening tests, medical imaging and is usually treated with chemotherapy, radiation therapy and surgery. With the advancement in medical sciences, targeted cancer therapy has got lot of importance which has many benefits, comforts and patient friendly as compared to conventional therapies. This review gives an insight of the various targeted therapies, their role and impact in treatment of various types of cancers. Targeted cancer therapies like monoclonal antibodies, nanoparticle-aptamer bioconjugates, oligopeptide-based, folate-based, AdNectins, microfluidics and nanotechnology approaches have led to deliver target- oriented toxic ...

DARU Journal of Pharmaceutical Sciences, 2013

Background: A specific and sensitive UPLC-qTOF-MS/MS method has been developed for the simultaneo... more Background: A specific and sensitive UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of curcuminoids. These Curcuminoids comprises of curcumin, a principal curcuminoid and other two namely, demethoxycurcumin, and bisdemethoxycurcumin obtained from rhizomes of Curcuma longa an ancient Indian curry spice turmeric, family (Zingiberaceae). Methods: These analytes were separated on a reverse phase C18 column by using a mobile phase of acetonitrile: 5% acetonitrile in water with 0.07% acetic acid (75:25 v/v), flow rate of 100 μL/min was maintained. The qTOF-MS was operated under multiple reaction monitoring (MRM) mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions in the positive mode for curcuminoids were at m/z 369.1066, 339.1023 and 309.0214 respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. Results: The total run time was 5 min and the peaks of the compounds, bisdemethoxycurcumin, demethoxycurcumin and curcumin occurred at 2.06, 2.23 and 2.40 min respectively. The calibration curves of bisdemethoxycurcumin, demethoxycurcumin and curcumin were linear over the concentration range of 2-1000 ng/mL (r2, 0.9951), 2-1000 ng/mL (r2, 0.9970) and 2-1000 ng/mL (r2, 0.9906) respectively. Intra-assay and inter-assay accuracy in terms of % bias for curcumin was in between −7.95to +6.21, and −7.03 to + 6.34; for demethoxycurcumin was −6.72 to +6.34, and −7.86 to +6.74 and for bisdesmetoxycurcumin was −8.23 to +6.37 and −8.47 to +7.81. The lower limit of quantitation for curcumin, demethoxycurcumin and bisdemethoxycurcumin was 2.0 ng/mL. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). This validated method was used during pharmacokinetic studies of curcumin in the mouse plasma.

Reproduction, 1980

An intrauterine copper device stimulated endogenous hydrogen peroxide formation in whole homogena... more An intrauterine copper device stimulated endogenous hydrogen peroxide formation in whole homogenates and in the mitochondrial and microsomal (but not the nuclear) fractions of rat endometrial tissues. Uric acid also accumulated in the endometrium of copper-treated rats, but not in those fitted with a nylon device or sham operated. It is suggested that the contraceptive effect of copper may be related to these events.

Phytomedicine, 1999

Piperine (l-Piperoyl piperidine) is the major alkaloid of black and long peppers used widely in v... more Piperine (l-Piperoyl piperidine) is the major alkaloid of black and long peppers used widely in various systems of traditional medicine. The present study investigates the toxicity of piperine via free-radical generation by determining the degree of lipid peroxidation and cellular thiol status in the rat intestine. Lipid peroxidation content, measured as thiobarbituric reactive substances (TBARS), was increased with piperine treatment although conjugate diene levels were not altered. A significant increase in glutathione levels was observed, whereas protein thiols and glutathione reductase activity were not altered. The study suggests that increased TBARS levels may not be a relevant index of cytotoxicity, since thiol redox was not altered, but increased synthesis transport of intracellular GSH pool may play an important role in cell hemostasis and requires further study.

Journal of Ethnopharmacology, 2001

Swertia chirata Buch-Ham. (Gentianaceae), one of the oldest medicinal herbs of India, is a source... more Swertia chirata Buch-Ham. (Gentianaceae), one of the oldest medicinal herbs of India, is a source of the Indian ayurvedic drug 'chirata' used for the treatment of liver disorders and malarial fevers. In this study, eight species of Swertia were collected. Each of the dry whole plant was extracted into methanol, the aqueous extract of which was sequentially extracted into hexane, chloroform and butanol extracts. The extracts were screened for their anti-hepatotoxic activity against carbon tetrachloride (CCl 4) and paracetamol (acetaminophen (AAP)) toxicity in primary monolayer cultures of rat hepatocytes. The primary cultures, 2.5 × 10 6 cells /3 ml medium/60 mm collagen-coated plates, were exposed to 2.5 mM CCl 4 or 12 mM AAP in the presence or absence of plant extracts (100 mg/ml culture medium). Cells and medium were harvested after 22 h of treatment for the assay of cellular reduced gluthathione (GSH) content and leakage of lactate dehydrogenase as biological end-points of toxicity. Both CCl 4 and AAP at the indicated concentrations reduced GSH by almost 50 and 80%, respectively, while the enzyme leakage was almost 15% above the untreated control. Hexane and methanol extracts of most of the species in general offered relatively good protection. The anti-hepatotoxic activity, nevertheless, was evident in all Swertia species against both the toxicants. However, Swertia purpurascens, Swertia chirata, Swertia paniculata and Swertia cordata exhibited better activity compared with other species investigated. In addition, influence of various extracts (10-100 mg/ml medium) was examined on cellular growth of rat Reuber hepatoma cell line H4IIEC3/G −. Except for the butanol extract of S. chirata, no other extracts exerted toxicity in terms of neutral red uptake by the cells.

Journal of Ethnopharmacology, 1992

'Trikatu' is an Ayurvedic preparation containing black pepper, long pepper and gi... more 'Trikatu' is an Ayurvedic preparation containing black pepper, long pepper and ginger, which is prescribed routinely for a variety of diseases as part of a multidrug prescription. These herbs along with piperine (alkaloid of peppers) have been shown to possess diverse biological activities in mammalian systems. A review is presented of these studies and it has been suggested that their use in the Indian system of medicine could be due to their bioavailability enhancing action on other medicaments.

Journal of Endocrinology, 1980

The production of hydrogen peroxide was quantitated in the uterus of cyclic, ovariectomized (trea... more The production of hydrogen peroxide was quantitated in the uterus of cyclic, ovariectomized (treated with hormones) and pregnant (days 1–6 post coitum) rats. This phenomenon was found to be dependent on oestrogen. The uterine responsiveness to hydrogen peroxide was correlated with peroxidase-catalysed inactivation of oestrogens in this target organ.

Journal of Chromatography B, 2010

In the present investigation, a UPLC-qTOF-MS/MS method has been developed for the simultaneous de... more In the present investigation, a UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of etoposide and a piperine analogue, namely, 4-ethyl 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1). The analytes were separated on a reverse phase C18 column using methanol-water (72:28, v/v) mobile phase with a flow rate of 250 microL/min. The qTOF-MS was operated under multiple reaction monitoring mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions for etoposide and PA-1 were at m/z 185.1350 and 164.1581, respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. The total run time was 6 min and the elution of etoposide and PA-1 occurred at 1.24 and 2.84 min, respectively. The calibration curves of etoposide as well as PA-1 were linear over the concentration range of 2-1000 ng/mL (r(2), 0.9829), and 1-1000 ng/mL (r(2), 0.9989), respectively. For etoposide intra-assay and inter-assay accuracy in terms of % bias was in between -7.65 to +6.26, and -7.83 to +5.99, respectively. For PA-1 intra-assay and inter-assay accuracy in terms of % bias was in between -7.01 to +9.10, and -7.36 to +6.71, respectively. The lower limit of quantitation for etoposide and PA-1 were 2.0 and 1.0 ng/mL, respectively. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). The method was used for a pharmacokinetic study which showed that PA-1 enhanced the oral bioavailability of etoposide in mice by 2.32-fold.

Journal of Biosciences, 2014

Etoposide, a semi-synthetic derivative of podophyllotoxin, is one of the most active and useful a... more Etoposide, a semi-synthetic derivative of podophyllotoxin, is one of the most active and useful antineoplastic agent used routinely in firstline combination chemotherapy of testicular cancer, small-cell lung cancer and non-Hodgkin's lymphoma. Etoposide displays narrow therapeutic index, erratic pharmacokinetics and dose individualization that needs to be achieved for overcoming inter-and intra-patient variability (25-80%), so as to maintain proper drug exposure within a therapeutic range. Etoposide posses high plasma protein binding (97%) and is degraded via complex metabolic pathways. The main pharmacokinetic determinants of etoposide are still not completely defined in order to optimize the pharmaco-therapeutic parameters including dose, therapeutic schedule and route of administration. Much research has been done to determine drug-drug and herb-drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter-and intra-patient variability for improving the bioavailability of etoposide.

Journal of Biosciences, 1980

Activities of Phosphorylase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, mal... more Activities of Phosphorylase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, malate dehydrogenase and succinate dehydrogenase in the rat endometrial tissue are significantly inhibited by an intrauterine copper device, while it stimulated glucose-6phosphate dehydrogenase activity. The copper device decreased the lactate/pyruvate ratio in the tissue; pyruvate utilization in vitro by the rat endometrium is also blocked by copper. These findings suggested that the normal carbohydrate metabolism of the tissue may be affected in presence of copper, thus resulting in a change of the endometrial function, which may be one of the factors responsible for the contraceptive and pharmacological action of an intrauterine copper device.

Hepatology Research, 2007

Biochemical characterization of long-term toxic manifestations of anti-tubercular (anti-TB) drugs... more Biochemical characterization of long-term toxic manifestations of anti-tubercular (anti-TB) drugs - rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) - individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats. Animals received anti-TB drugs - alone or in combination - once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+-ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule. Anti-TB drugs-treated animals showed abnormal rises or falls (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1.5-2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15-90 days. The in vivo results were further supported by in vitro results (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. RESULTS indicated that anti-TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant-antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1-mediated bioactivation mechanism. Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis.

Hepatology Research, 2005

In the present study, the biochemical manifestations of liver toxicity caused by co-administratio... more In the present study, the biochemical manifestations of liver toxicity caused by co-administration of anti-TB drugs, rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA), in a sub-chronic mode (12 weeks), were investigated. Significant alterations were revealed in (a) increased levels of alanine aminotrasferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and a high bilirubin content in serum; (b) elevated lipid peroxidation (LPO), intracellular calcium [Ca(2+)](i) and CYP4502EI activity in liver; and (c) decreased glutathione (GSH) content, glutathione peroxidase (GPx) and catalase activities in liver. Silymarin reversed these abnormal alterations. The biochemical changes were supported by histological observations.

European Journal of Pharmacology, 2013

In the present investigation, adjuvant potential of two novel lipidated tripeptide lysine derivat... more In the present investigation, adjuvant potential of two novel lipidated tripeptide lysine derivatives (KKSM and KKSMB) was evaluated using various in vitro and animal-derived models of humoral and cell-mediated immune events in response to hepatitis B surface antigen (HBsAg). The results were compared with alum adjuvanted with HBsAg. Both these molecules were found to stimulate anti-HBsAg IgG and neutralizing (IgG1 and IgG2a) antibody titres in mice sera. The two molecules stimulated the proliferation of T-lymphocyte sub-sets (CD4/CD8) as well as the production of soluble mediators of Th1 (IL-2 and IFN-γ) and Th2 response (IL-4) in spleen cell culture supernatant. Furthermore, the two lipidated tripeptides enhanced the CD4, CD8, CD3 and CD19 cell populations as well as CD4/CD8 derived IL-2, IL-4, IFN-γ and TNF-α in whole blood of treated mice. There was found to be the significant enhancement in the release of IL-12, IFN-γ and nitrite content in macrophage supernatant. Moreover, the two lipidated tripeptides enhanced the population of CD80 and CD86 in spleen-derived macrophages and did not show any hemolytic effect on rabbit RBCs. Taken together, these results suggest that both these molecules are the potent enhancers of anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner.

Environmental Toxicology and Pharmacology, 2013

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid pi... more An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.

Biochemical Pharmacology, 1992

The effect of piperine (1-[5-(1,3-benzodioxol-5-yl)-l-oxo-2,4-~ntadienyl]pi~~dine}, (from Piper n... more The effect of piperine (1-[5-(1,3-benzodioxol-5-yl)-l-oxo-2,4-~ntadienyl]pi~~dine}, (from Piper nigrum) on the absorptive function of the intestine was studied. In vitro experiments showed that pipe&e (25-100 #&l) sign~cantly stimulated y-gfutamyl ~ans~ptid~ (y-GT, EC 2.3.2.2.) activity, enhanced the uptake of radiolabelled L-leucine, L-isoleucine and L-valine, and increased lipid peroxidation in freshly isolated epithelial cells of rat jejunum. The kinetic behaviour of y-GT towards substrate and acceptor altered in the presence of piperine. In the presence of benzyl alcohol, an enhanced y-GT activity due to piperine was maintained. These results suggested that piperine may interact with the lipid environment to produce effects which lead to increased permeability of the intestinal cells.

Biological & Pharmaceutical Bulletin, 2005

A hydroalcoholic (50%) extract of Emblica officinalis (fruit) (EO-50) reduced the severity of hep... more A hydroalcoholic (50%) extract of Emblica officinalis (fruit) (EO-50) reduced the severity of hepatic fibrosis induced by carbon tetrachloride (CCl 4) and thioacetamide (TAA). Improved liver function was observed by measuring the levels of aspartate aminotransaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin in serum. Hepatic parameters monitored were the levels of glutathione (GSH), lipid peroxidation (LPO) and hydroxyproline and the activities of catalase, glutathione peroxidase (GPx), Na ؉ ,K ؉-ATPase and cytochrome P450 (CYP 450 2E1) (aniline hydroxylation). The results suggested that EO-50 effectively reversed profibrogenic events possibly due to its promising antioxidative activity.