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Papers by bhaswati banerjee

Journal of Food Biochemistry, 2020

The present study explored the ameliorative potency of aqueous extract of Capsicum annum (AqCA), ... more The present study explored the ameliorative potency of aqueous extract of Capsicum annum (AqCA), against oxidative imbalance and renal toxicity induced by ethanol. Randomly grouped male Wistar rats (n = 6), were marked as ethanol-treated (2 g/kg bw, i.p.), CA125 (125 mg/kg bw, i.p.), CA250 (250 mg/kg bw, i.p.), ethanol pre-treated with CA (similar doses), and control (0.5 ml normal saline, i.p.), and treated for 30 consecutive days. Biochemical analysis of tissue and serum parameters was performed, along with histopathological and histochemical studies. Also, we performed TUNEL assay and western blotting for our experimental groups. Statistical analysis revealed significant (p ≤ .001) alteration in the levels of antioxidant enzymes, serum urea, creatinine, pro-inflammatory cytokines, and cleaved caspases, along with histopathological alterations in the ethanol-treated group. Prior treatment with AqCA prevented ethanol-induced alterations in tissue and serum parameters. These findings indicate that the extract of CA can protect renal cells from ethanol-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis. PRACTICAL APPLICATIONS: Chronic alcohol consumption is a major public health concern that leads to various diseases and social problems as well. It affects both the affluent and non-affluent society equally. Alcohol (ethanol) is a renowned hepato-toxicant and a well-documented risk factor for oxidative stress, with less known effect on the kidney. Thus, it is essential to investigate the effect of alcohol metabolism on the kidney to find a remedy to prevent it. The present investigation depicts the anti-oxidative and anti-inflammatory role of Capsicum annum against ethanol-induced renal damage. The outcome of this study can be utilized in the future for phytotherapeutic herbal drug formulation. Besides, the bioactive components identified in the study can be further explored by researchers or pharmaceutical corporates for potential therapeutic purpose against renal impairment.

The FASEB Journal, 2007

We formulate the Riemannian calculus of the probability set embedded with L 2-Wasserstein metric.... more We formulate the Riemannian calculus of the probability set embedded with L 2-Wasserstein metric. This is an initial work of transport information geometry. Our investigation starts with the probability simplex (probability manifold) supported on vertices of a finite graph. The main idea is to embed the probability manifold as a submanifold of the positive measure space with a nonlinear metric tensor. Here the nonlinearity comes from the linear weighted Laplacian operator. By this viewpoint, we establish torsion-free Christoffel symbols, Levi-Civita connections, curvature tensors and volume forms in the probability manifold by Euclidean coordinates. As a consequence, the Jacobi equation, Laplace-Beltrami and Hessian operators on the probability manifold are derived. These geometric computations are also provided in the infinite-dimensional density space (density manifold) supported on a finite-dimensional manifold. In particular, an identity is given connecting the Baker-Émery Γ2 operator (carré du champ itéré) by connecting Fisher-Rao information metric and optimal transport metric. Several examples are demonstrated.

Frontiers in Endocrinology, 2019

Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exe... more Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exerts male reproductive dysfunctions. In this study the molecular mechanism of B(a)P induced Leydig cell steroidogenic dysfunctions and its protective mechanism of action with a natural Aryl hydrocarbon receptor (AhR) antagonist and anti-oxidant, Resveratrol (Res) has been investigated. B(a)P exposure induced ROS mediated steroidogenic imbalance via activation of p38MAPK and repression of testosterone level as well as other steroidogenic enzymes like CYPIIA1, 3β-HSD, 17β-HSD expressions. B(a)P exposure decreased StAR protein expression along with increased DAX-1, a transcriptional repressor of StAR gene. Along with that B(a)P decreased the expression of SF-1 that acts as a transcriptional inducer of StAR gene expression. The study has established Resveratrol as a potential agent combating the deleterious effect of B(a)P on Leydig cell steroidogenesis. Resveratrol treatment resulted significant protection against B(a)P by scavenging ROS and modulating the transcriptional regulation of anti-oxidant enzymes. Furthermore, Resveratrol also prevented stress kinase like p38 MAPK activation and increased StAR protein expression through the reduction of DAX-1 expression. Moreover, the testosterone production was efficiently restored with Resveratrol treatment. ChIP assay also revealed that resveratrol improved SF-1expression which further increased the StAR gene expression. Resveratrol acted efficiently against B(a)P, through its anti-oxidative properties as well as inhibits p38MAPK and increased steroidogenesis and StAR expression through the modulation of SF-1 gene expression.

Journal of Ethnopharmacology, 2018

ETHNOPHARMACOLOGICAL RELEVANCE Capsicum annum L. (CA) is used extensively as a spice and is a ric... more ETHNOPHARMACOLOGICAL RELEVANCE Capsicum annum L. (CA) is used extensively as a spice and is a rich source of antioxidant vitamins. It has long been used in Indian, Native American, and Chinese traditional medicine as a carminative and an appetizer that normalizes liver function. However, its hepato-protective activity has so far not been studied. AIM OF THE STUDY The present study was undertaken to evaluate the efficacy of aqueous extract of CA at two different doses (125 mg/kg body weight and 250 mg/kg body weight), against ethanol induced oxidative stress and apoptosis in liver tissue. MATERIALS AND METHODS Adult male Wistar rats, weighing 150-200 g, were randomly grouped (n = 6) and treated with ethanol (2 g/kg bw, i.p.), CA125 (125 mg/kg bw, i.p.), CA250 (250 mg/kg bw, i.p.), ethanol with CA (similar doses), and control (0.5 ml normal saline, i.p.) for 30 days. Lipid peroxidation (LPO) and reduced glutathione content (GSH) in tissue homogenate, along with catalase (CAT), superoxide dismutase (Cu-Zn-SOD & Mn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST) and glucose-6-phosphate dehydrogenase (G-6-P-D) activity were evaluated. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphate (ALP), triglyceride (TG), total cholesterol (CHLS), high density lipoprotein (HDL), low density lipoprotein (LDL) very low density lipoprotein (VLDL), tumour necrotic factor alpha (TNF-α) and interleukin 6 (IL-6) were also measured using ELISA kits. Histopathological evaluation of the hepatic tissue was performed by hematoxylin and eosin (H&E) and periodic acid-schiff (PAS) staining. TUNEL assay was performed for apoptosis detection. RESULTS Ethanol significantly (p < 0.001) increased ALT, AST, ALP, TNF-α, IL-6, LPO, Cu-Zn-SOD, GST, GPx, TG, CHLS, LDL, VLDL levels, along with significant (p < 0.001) decrease in HDL, Mn-SOD, CAT, GSH, GR and G6PD activity. Co-administration of CA along with ethanol alleviated changes in the above parameters (p < 0.001) in a dose-dependent manner and also reduced the number of apoptotic death cells. Histo-pathological and histo-chemical studies of liver sections also ascertained the outcomes of this study. CONCLUSION Thus, it can be concluded that the aqueous extract of green CA can exert a protective effect against ethanol induced hepato-toxicity. The possible mechanism may be by acting as an antioxidant; preventing ethanol induced apoptosis and reducing pro-inflammatory cytokine levels.

Toxicology and industrial health, 2018

Lambda cyhalothrin (LCT) is a type II pyrethroid with a wide range of agricultural, industrial, a... more Lambda cyhalothrin (LCT) is a type II pyrethroid with a wide range of agricultural, industrial, and household uses. Taurine is a nonprotein sulfur containing amino acid as well as a well-known antioxidant and has valuable clinical applications in the detoxification of xenobiotics. The present study evaluated the effect of LCT on the reproductive and endocrine systems of female rats and determined whether taurine might alter these effects. Sexually mature female rats were administered LCT at two different dosages (6.3 mg/kg BW and 11.33 mg/kg BW) once daily by oral gavage for 14 consecutive days with the pretreatment of taurine (50 mg kgBW). LCT treatment resulted in diminished adrenal cholesterol, ovarian 3β- and 17β-hydroxysteroid dehydrogenase (HSD) activity with increased ovarian cholesterol, adrenal 3β- and 17β-HSD activity. Furthermore, protein and mRNA expressions of ovarian 17β-HSD and steroidogenic acute regulatory protein were also decreased. Hormonal imbalance was evident ...

Apoptosis, 2016

The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therape... more The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3 0-(Arylmethylene)bis-1H-indole (AMBI) derivative 3,3 0-[(4-Methoxyphenyl) methylene]-bis-(5-bromo-1H-indole), named as Mephebrindole (MPB) as an effective anti-cancer agent in breast cancer cells. MPB disrupted calcium homeostasis in MCF7 cells which triggered ER stress development. Detailed evaluations revealed that mephebrindole by activating p38MAPK also regulated GRP78 and eIF2a/ATF4 downstream to promote apoptosis. Studies extended to in vivo allograft mice models revalidated its anti-carcinogenic property thus highlighting the role of MPB as an improved chemotherapeutic option. Keywords Breast cancer Á Calcium Á Unfolded protein response Á ER stress Á p38MAPK Á Reactive oxygen species Abbreviations MPB Mephebrindole UPR Unfolded protein response ER stress Endoplasmic reticulum stress GRP78 Glucose regulated protein 78 ATF4 Activating transcription factor 4 CHOP CCAAT-enhancer-binding protein homologous protein eIF2a Eukaryotic initiation factor 2a ChIP Chromatin immunoprecipitation p38 MAPK p38 Mitogen activated protein kinase AMBI Aryl methyl bis-indolyl derivative NAC N-Acetyl cysteine Electronic supplementary material The online version of this article (

Frontiers in Pharmacology, 2016

Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcum... more Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and antioxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcuminresveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol cotreatment actively protected B(a)P induced testicular germ cell apoptosis. Curcuminresveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol cotreatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Frontiers in Pharmacology, 2016

Nanomedicine: Nanotechnology, Biology and Medicine, 2016

Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women,... more Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women, associated with poor prognosis. Standard chemotherapy targets all dividing cells, resulting in dose-limiting toxicities. In this study, we demonstrated a strategy of encapsulating a hydrophobic synthetic compound, nifetepimine, having anticancer properties, in poly (lactic-co-glycolic acid) nanoparticles to increase selectivity of drug to cancerous cells with minimum toxicity towards normal cells. Nanoencapsulated nifetepimine (30-100 nm) having loading and encapsulation efficiency of 7.45% and 75% respectively, was successfully internalized inside TNBC cells upon sustained release resulting in apoptosis. An in vivo bio-distribution study indicated that nanonifetepimine selectively accumulated into breast tumor sites of mice, primarily due to prolonged blood circulation time and binding of nifetepimine to epidermal growth factor receptor that remains overexpressed in most of the TNBC tumors. Moreover, we observed significant reduction in breast tumor volume with improved survival implying high tumor targetability of nanonifetepimine.

Translational Medicine, 2013

An enormous body of evidence supports the activation of caspases may be responsible for the neuro... more An enormous body of evidence supports the activation of caspases may be responsible for the neurodegeneration associated with Alzheimer's disease (AD) and for that reason, caspases are potential therapeutic targets for the management of this disorder. However, till date, the studies testing with prospective role of caspase inhibitors for the treatment of AD have yet to be realized. Obviously, this is due to the potential side effects due to long term use of caspase inhibitors. In addition, a further assessment is warned in relation to the therapeutic efficacy and stress of targeting caspase inhibition with the potential caspase inhibitors and its improved delivery system to the brain in the treatment of AD.

Toxicology Reports, 2014

Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3carboxamide), a clas... more Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3carboxamide), a classical non-steroidal anti-inflammatory drug (NSAID) is orally administered to arthritic patients. Inhibition of prostaglandin E 2 (PGE 2) synthesis and subsequent free hydroxyl radical generation in vivo exert gastro-toxic side effects on piroxicam treatment. Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led us to investigate the efficiency of the use of curry leaves in ameliorating piroxicam induced gastric damage. Piroxicam was orally (30 mg per kg body weight) administered in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves (Cu LE) prior to piroxicam administration. Oxidative stress biomarkers, activities of antioxidant and pro-oxidant enzymes, mucin content and nature, PGE 2 level, activities of mitochondrial enzymes and histomorphology of gastric tissues were studied. Piroxicam treatment altered all the above mentioned parameters whereas, curry leaf extract pre-treated animals were protected against piroxicam induced alterations. Hence, the protective action of the antioxidant rich Cu LE was investigated to propose a new combination therapy or dietary management to arthritic patients using piroxicam.

PLoS Pathogens, 2007

The ability of Plasmodium falciparum-infected red blood cells (IRBCs) to bind to vascular endothe... more The ability of Plasmodium falciparum-infected red blood cells (IRBCs) to bind to vascular endothelium, thus enabling sequestration in vital host organs, is an important pathogenic mechanism in malaria. Adhesion of P. falciparum IRBCs to platelets, which results in the formation of IRBC clumps, is another cytoadherence phenomenon that is associated with severe disease. Here, we have used in vitro cytoadherence assays to demonstrate, to our knowledge for the first time, that P. falciparum IRBCs use the 32-kDa human protein gC1qR/HABP1/p32 as a receptor to bind to human brain microvascular endothelial cells. In addition, we show that P. falciparum IRBCs can also bind to gC1qR/HABP1/p32 on platelets to form clumps. Our study has thus identified a novel host receptor that is used for both adhesion to vascular endothelium and platelet-mediated clumping. Given the association of adhesion to vascular endothelium and plateletmediated clumping with severe disease, adhesion to gC1qR/HABP1/p32 by P. falciparum IRBCs may play an important role in malaria pathogenesis.

Cell Research, 2005

Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein wi... more Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.

The Journal of nutritional biochemistry, Jan 25, 2016

Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of test... more Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction. Resveratrol cotreatment maintained testicular redox potential, increased serum testosterone level and enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3βHSD, 17βHSD) and prevented subsequent onset of apoptosis. Resveratrol cotreatment resulted inhibition of testicular cytochrome P4501A1 (CYP1A1) expression, which is the major B(a)P metabolizing agent for BPDE-DNA adduct formation. Resveratrol ...

Journal of Food Biochemistry, 2020

The present study explored the ameliorative potency of aqueous extract of Capsicum annum (AqCA), ... more The present study explored the ameliorative potency of aqueous extract of Capsicum annum (AqCA), against oxidative imbalance and renal toxicity induced by ethanol. Randomly grouped male Wistar rats (n = 6), were marked as ethanol-treated (2 g/kg bw, i.p.), CA125 (125 mg/kg bw, i.p.), CA250 (250 mg/kg bw, i.p.), ethanol pre-treated with CA (similar doses), and control (0.5 ml normal saline, i.p.), and treated for 30 consecutive days. Biochemical analysis of tissue and serum parameters was performed, along with histopathological and histochemical studies. Also, we performed TUNEL assay and western blotting for our experimental groups. Statistical analysis revealed significant (p ≤ .001) alteration in the levels of antioxidant enzymes, serum urea, creatinine, pro-inflammatory cytokines, and cleaved caspases, along with histopathological alterations in the ethanol-treated group. Prior treatment with AqCA prevented ethanol-induced alterations in tissue and serum parameters. These findings indicate that the extract of CA can protect renal cells from ethanol-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis. PRACTICAL APPLICATIONS: Chronic alcohol consumption is a major public health concern that leads to various diseases and social problems as well. It affects both the affluent and non-affluent society equally. Alcohol (ethanol) is a renowned hepato-toxicant and a well-documented risk factor for oxidative stress, with less known effect on the kidney. Thus, it is essential to investigate the effect of alcohol metabolism on the kidney to find a remedy to prevent it. The present investigation depicts the anti-oxidative and anti-inflammatory role of Capsicum annum against ethanol-induced renal damage. The outcome of this study can be utilized in the future for phytotherapeutic herbal drug formulation. Besides, the bioactive components identified in the study can be further explored by researchers or pharmaceutical corporates for potential therapeutic purpose against renal impairment.

The FASEB Journal, 2007

We formulate the Riemannian calculus of the probability set embedded with L 2-Wasserstein metric.... more We formulate the Riemannian calculus of the probability set embedded with L 2-Wasserstein metric. This is an initial work of transport information geometry. Our investigation starts with the probability simplex (probability manifold) supported on vertices of a finite graph. The main idea is to embed the probability manifold as a submanifold of the positive measure space with a nonlinear metric tensor. Here the nonlinearity comes from the linear weighted Laplacian operator. By this viewpoint, we establish torsion-free Christoffel symbols, Levi-Civita connections, curvature tensors and volume forms in the probability manifold by Euclidean coordinates. As a consequence, the Jacobi equation, Laplace-Beltrami and Hessian operators on the probability manifold are derived. These geometric computations are also provided in the infinite-dimensional density space (density manifold) supported on a finite-dimensional manifold. In particular, an identity is given connecting the Baker-Émery Γ2 operator (carré du champ itéré) by connecting Fisher-Rao information metric and optimal transport metric. Several examples are demonstrated.

Frontiers in Endocrinology, 2019

Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exe... more Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exerts male reproductive dysfunctions. In this study the molecular mechanism of B(a)P induced Leydig cell steroidogenic dysfunctions and its protective mechanism of action with a natural Aryl hydrocarbon receptor (AhR) antagonist and anti-oxidant, Resveratrol (Res) has been investigated. B(a)P exposure induced ROS mediated steroidogenic imbalance via activation of p38MAPK and repression of testosterone level as well as other steroidogenic enzymes like CYPIIA1, 3β-HSD, 17β-HSD expressions. B(a)P exposure decreased StAR protein expression along with increased DAX-1, a transcriptional repressor of StAR gene. Along with that B(a)P decreased the expression of SF-1 that acts as a transcriptional inducer of StAR gene expression. The study has established Resveratrol as a potential agent combating the deleterious effect of B(a)P on Leydig cell steroidogenesis. Resveratrol treatment resulted significant protection against B(a)P by scavenging ROS and modulating the transcriptional regulation of anti-oxidant enzymes. Furthermore, Resveratrol also prevented stress kinase like p38 MAPK activation and increased StAR protein expression through the reduction of DAX-1 expression. Moreover, the testosterone production was efficiently restored with Resveratrol treatment. ChIP assay also revealed that resveratrol improved SF-1expression which further increased the StAR gene expression. Resveratrol acted efficiently against B(a)P, through its anti-oxidative properties as well as inhibits p38MAPK and increased steroidogenesis and StAR expression through the modulation of SF-1 gene expression.

Journal of Ethnopharmacology, 2018

ETHNOPHARMACOLOGICAL RELEVANCE Capsicum annum L. (CA) is used extensively as a spice and is a ric... more ETHNOPHARMACOLOGICAL RELEVANCE Capsicum annum L. (CA) is used extensively as a spice and is a rich source of antioxidant vitamins. It has long been used in Indian, Native American, and Chinese traditional medicine as a carminative and an appetizer that normalizes liver function. However, its hepato-protective activity has so far not been studied. AIM OF THE STUDY The present study was undertaken to evaluate the efficacy of aqueous extract of CA at two different doses (125 mg/kg body weight and 250 mg/kg body weight), against ethanol induced oxidative stress and apoptosis in liver tissue. MATERIALS AND METHODS Adult male Wistar rats, weighing 150-200 g, were randomly grouped (n = 6) and treated with ethanol (2 g/kg bw, i.p.), CA125 (125 mg/kg bw, i.p.), CA250 (250 mg/kg bw, i.p.), ethanol with CA (similar doses), and control (0.5 ml normal saline, i.p.) for 30 days. Lipid peroxidation (LPO) and reduced glutathione content (GSH) in tissue homogenate, along with catalase (CAT), superoxide dismutase (Cu-Zn-SOD & Mn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST) and glucose-6-phosphate dehydrogenase (G-6-P-D) activity were evaluated. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphate (ALP), triglyceride (TG), total cholesterol (CHLS), high density lipoprotein (HDL), low density lipoprotein (LDL) very low density lipoprotein (VLDL), tumour necrotic factor alpha (TNF-α) and interleukin 6 (IL-6) were also measured using ELISA kits. Histopathological evaluation of the hepatic tissue was performed by hematoxylin and eosin (H&E) and periodic acid-schiff (PAS) staining. TUNEL assay was performed for apoptosis detection. RESULTS Ethanol significantly (p < 0.001) increased ALT, AST, ALP, TNF-α, IL-6, LPO, Cu-Zn-SOD, GST, GPx, TG, CHLS, LDL, VLDL levels, along with significant (p < 0.001) decrease in HDL, Mn-SOD, CAT, GSH, GR and G6PD activity. Co-administration of CA along with ethanol alleviated changes in the above parameters (p < 0.001) in a dose-dependent manner and also reduced the number of apoptotic death cells. Histo-pathological and histo-chemical studies of liver sections also ascertained the outcomes of this study. CONCLUSION Thus, it can be concluded that the aqueous extract of green CA can exert a protective effect against ethanol induced hepato-toxicity. The possible mechanism may be by acting as an antioxidant; preventing ethanol induced apoptosis and reducing pro-inflammatory cytokine levels.

Toxicology and industrial health, 2018

Lambda cyhalothrin (LCT) is a type II pyrethroid with a wide range of agricultural, industrial, a... more Lambda cyhalothrin (LCT) is a type II pyrethroid with a wide range of agricultural, industrial, and household uses. Taurine is a nonprotein sulfur containing amino acid as well as a well-known antioxidant and has valuable clinical applications in the detoxification of xenobiotics. The present study evaluated the effect of LCT on the reproductive and endocrine systems of female rats and determined whether taurine might alter these effects. Sexually mature female rats were administered LCT at two different dosages (6.3 mg/kg BW and 11.33 mg/kg BW) once daily by oral gavage for 14 consecutive days with the pretreatment of taurine (50 mg kgBW). LCT treatment resulted in diminished adrenal cholesterol, ovarian 3β- and 17β-hydroxysteroid dehydrogenase (HSD) activity with increased ovarian cholesterol, adrenal 3β- and 17β-HSD activity. Furthermore, protein and mRNA expressions of ovarian 17β-HSD and steroidogenic acute regulatory protein were also decreased. Hormonal imbalance was evident ...

Apoptosis, 2016

The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therape... more The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3 0-(Arylmethylene)bis-1H-indole (AMBI) derivative 3,3 0-[(4-Methoxyphenyl) methylene]-bis-(5-bromo-1H-indole), named as Mephebrindole (MPB) as an effective anti-cancer agent in breast cancer cells. MPB disrupted calcium homeostasis in MCF7 cells which triggered ER stress development. Detailed evaluations revealed that mephebrindole by activating p38MAPK also regulated GRP78 and eIF2a/ATF4 downstream to promote apoptosis. Studies extended to in vivo allograft mice models revalidated its anti-carcinogenic property thus highlighting the role of MPB as an improved chemotherapeutic option. Keywords Breast cancer Á Calcium Á Unfolded protein response Á ER stress Á p38MAPK Á Reactive oxygen species Abbreviations MPB Mephebrindole UPR Unfolded protein response ER stress Endoplasmic reticulum stress GRP78 Glucose regulated protein 78 ATF4 Activating transcription factor 4 CHOP CCAAT-enhancer-binding protein homologous protein eIF2a Eukaryotic initiation factor 2a ChIP Chromatin immunoprecipitation p38 MAPK p38 Mitogen activated protein kinase AMBI Aryl methyl bis-indolyl derivative NAC N-Acetyl cysteine Electronic supplementary material The online version of this article (

Frontiers in Pharmacology, 2016

Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcum... more Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and antioxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcuminresveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol cotreatment actively protected B(a)P induced testicular germ cell apoptosis. Curcuminresveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol cotreatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Frontiers in Pharmacology, 2016

Nanomedicine: Nanotechnology, Biology and Medicine, 2016

Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women,... more Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women, associated with poor prognosis. Standard chemotherapy targets all dividing cells, resulting in dose-limiting toxicities. In this study, we demonstrated a strategy of encapsulating a hydrophobic synthetic compound, nifetepimine, having anticancer properties, in poly (lactic-co-glycolic acid) nanoparticles to increase selectivity of drug to cancerous cells with minimum toxicity towards normal cells. Nanoencapsulated nifetepimine (30-100 nm) having loading and encapsulation efficiency of 7.45% and 75% respectively, was successfully internalized inside TNBC cells upon sustained release resulting in apoptosis. An in vivo bio-distribution study indicated that nanonifetepimine selectively accumulated into breast tumor sites of mice, primarily due to prolonged blood circulation time and binding of nifetepimine to epidermal growth factor receptor that remains overexpressed in most of the TNBC tumors. Moreover, we observed significant reduction in breast tumor volume with improved survival implying high tumor targetability of nanonifetepimine.

Translational Medicine, 2013

An enormous body of evidence supports the activation of caspases may be responsible for the neuro... more An enormous body of evidence supports the activation of caspases may be responsible for the neurodegeneration associated with Alzheimer's disease (AD) and for that reason, caspases are potential therapeutic targets for the management of this disorder. However, till date, the studies testing with prospective role of caspase inhibitors for the treatment of AD have yet to be realized. Obviously, this is due to the potential side effects due to long term use of caspase inhibitors. In addition, a further assessment is warned in relation to the therapeutic efficacy and stress of targeting caspase inhibition with the potential caspase inhibitors and its improved delivery system to the brain in the treatment of AD.

Toxicology Reports, 2014

Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3carboxamide), a clas... more Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3carboxamide), a classical non-steroidal anti-inflammatory drug (NSAID) is orally administered to arthritic patients. Inhibition of prostaglandin E 2 (PGE 2) synthesis and subsequent free hydroxyl radical generation in vivo exert gastro-toxic side effects on piroxicam treatment. Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led us to investigate the efficiency of the use of curry leaves in ameliorating piroxicam induced gastric damage. Piroxicam was orally (30 mg per kg body weight) administered in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves (Cu LE) prior to piroxicam administration. Oxidative stress biomarkers, activities of antioxidant and pro-oxidant enzymes, mucin content and nature, PGE 2 level, activities of mitochondrial enzymes and histomorphology of gastric tissues were studied. Piroxicam treatment altered all the above mentioned parameters whereas, curry leaf extract pre-treated animals were protected against piroxicam induced alterations. Hence, the protective action of the antioxidant rich Cu LE was investigated to propose a new combination therapy or dietary management to arthritic patients using piroxicam.

PLoS Pathogens, 2007

The ability of Plasmodium falciparum-infected red blood cells (IRBCs) to bind to vascular endothe... more The ability of Plasmodium falciparum-infected red blood cells (IRBCs) to bind to vascular endothelium, thus enabling sequestration in vital host organs, is an important pathogenic mechanism in malaria. Adhesion of P. falciparum IRBCs to platelets, which results in the formation of IRBC clumps, is another cytoadherence phenomenon that is associated with severe disease. Here, we have used in vitro cytoadherence assays to demonstrate, to our knowledge for the first time, that P. falciparum IRBCs use the 32-kDa human protein gC1qR/HABP1/p32 as a receptor to bind to human brain microvascular endothelial cells. In addition, we show that P. falciparum IRBCs can also bind to gC1qR/HABP1/p32 on platelets to form clumps. Our study has thus identified a novel host receptor that is used for both adhesion to vascular endothelium and platelet-mediated clumping. Given the association of adhesion to vascular endothelium and plateletmediated clumping with severe disease, adhesion to gC1qR/HABP1/p32 by P. falciparum IRBCs may play an important role in malaria pathogenesis.

Cell Research, 2005

Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein wi... more Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.

The Journal of nutritional biochemistry, Jan 25, 2016

Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of test... more Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction. Resveratrol cotreatment maintained testicular redox potential, increased serum testosterone level and enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3βHSD, 17βHSD) and prevented subsequent onset of apoptosis. Resveratrol cotreatment resulted inhibition of testicular cytochrome P4501A1 (CYP1A1) expression, which is the major B(a)P metabolizing agent for BPDE-DNA adduct formation. Resveratrol ...