National Institute of Pharmaceutical Education and Research, Guwahati

www.niperguwahati.org
Guwahati, India

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PubMed | National Institute of Pharmaceutical Education and Research, Guwahati
Type: Journal Article | Journal: Environmental toxicology and pharmacology | Year: 2015

Diabetic nephropathy is a serious microvascular complication for patients associated with diabetes mellitus. Recent studies have suggested that NF-B is the main transcription factor for the inflammatory response mediated progression of diabetic nephropathy. Hence, the present study is hypothesized to explore the renoprotective nature of BAY 11-7082 an IB phosphorylation inhibitor on Streptozotocin (STZ) induced diabetic nephropathy in Sprague-Dawley (SD) rats. Male SD rats were divided into five groups, group I sham control, group II drug control, group III diabetic control (STZ 50mg/kg), group IV and V are test drug groups to which a single dose of STZ 50mg/kg was injected initially and later received BAY 11-7082 1mg/kg and 3mg/kg, respectively from 5th to 8th week. Eight weeks after STZ injection, diabetic rats exhibited significant renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, urea nitrogen and creatinine, which were reversed to near normal by BAY 11-7082. BAY 11-7082 treated rats showed significant improvement in the decreased enzymatic antioxidant SOD, non-enzymatic antioxidant GSH levels, and elevated lipid peroxidation and nitric oxide levels as observed in the diabetic rats. BAY 11-7082 treatment was found to significantly recover kidney histological architecture in the diabetic rats. Altered levels of inflammatory cytokines like TNF-, IL-1, IL-6 and nuclear transcriptional factor subunit NF-B p65 were reverted to the normal level upon treatment with BAY 11-7082. Our results suggest that by limiting the activation of NF-B, thereby reducing the expression of inflammatory cytokines and by inhibiting the oxidative damage BAY 11-7082 protect the rats against diabetic nephropathy.


PubMed | Gauhati Medical College, Maharshi Dayanand University and National Institute of Pharmaceutical Education and Research, Guwahati
Type: | Journal: European journal of pharmacology | Year: 2016

Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-B activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-B activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment.


Tyagi M.,National Institute of Pharmaceutical Education and Research, Guwahati | Kartha K.P.R.,National Institute of Pharmaceutical Education and Research, Guwahati
Carbohydrate Research | Year: 2015

Abstract Various carbohydrate-anchored triazole-linked lipids prepared by solvent-free mechanochemical azide-alkyne click reaction, on analysis by TEM, have been found to spontaneously self-assemble in solvents leading to structures of interesting physicochemical attributes. Interestingly, analogous compounds based on different sugars (e.g., d-glucose, and d-galactose, as also d-lactose) assemble in patterns distinctly different from each other thus reiterating the fact that the structure of the sugar as well as that of the lipid are important factors that determine the size and shape of the supramolecular assembly formed. Besides, the molecular self-assembly was also found to be solvent-as well as temperature-dependent. © 2015 Elsevier Ltd.


Mundhe N.A.,National Institute of Pharmaceutical Education and Research, Guwahati | Kumar P.,National Institute of Pharmaceutical Education and Research, Guwahati | Ahmed S.,National Institute of Pharmaceutical Education and Research, Guwahati | Jamdade V.,National Institute of Pharmaceutical Education and Research, Guwahati | And 2 more authors.
International Immunopharmacology | Year: 2015

Abstract Cisplatin is a widely used antineoplastic drug, but its clinical usefulness is limited due to dose dependent nephrotoxicity. Nordihydroguaiaretic acid (NDGA) is a natural compound with broad pharmacological properties like antioxidant, anti-inflammatory and anticancer activity. The present study was undertaken to evaluate the possible beneficial effects of NDGA on cisplatin induced nephrotoxicity as well as its anticancer activity in rats bearing DMBA induced mammary tumors. The effect of NDGA on cisplatin induced nephrotoxicity was evaluated by checking serum nephrotoxicity markers, antioxidant enzymes and inflammatory markers level and kidney histopathology. NDGA induced amelioration of cisplatin nephrotoxicity was clearly visible from significant reductions in serum blood urea nitrogen (86.51 g/dl) and creatinine (5.30 g/dl) levels and significant improvement in body weight change (- 10.34 g) and kidney weight (728 mg/kg). The protective effect of NDGA against cisplatin induced nephrotoxicity in the rats was further confirmed by significant restoration of antioxidant enzymes like SOD (86.28% inhibition), inflammatory markers like TNF-α (34.6 pg/ml) and histopathological examination. Moreover, our results showed that NDGA potentiated anti-breast cancer activity of cisplatin through an increment in the expression of antioxidant enzymes like SOD (85.35% inhibition) in breast cancer tissue. These results indicated that NDGA potentiated the anti-breast cancer activity of cisplatin, which was clearly evident from the tumor volume and % tumor inhibition in breast cancer rats. The current study demonstrated that NDGA may modify the therapeutic effect of cisplatin in DMBA induced breast cancer in female Sprague-Dawley rats. © 2015 Elsevier B.V.


PubMed | Bharati Vidyapeeth Deemed University, University of Kentucky, National Institute of Pharmaceutical Education and Research, Guwahati and Jamia Hamdard University
Type: Journal Article | Journal: Pharmaceutical biology | Year: 2016

Doxorubicin (Dox) is one of the most active chemotherapeutic agents used to treat various types of cancers. Its clinical utility is compromised due to fatal cardiac toxicity characterized by an irreversible cardiomyopathy.This study evaluates the cardioprotective potential of naringin (NR) against Dox-induced acute cardiac toxicity in rats.Male Wistar rats were randomly divided into five groups. NR (50 and 100mg/kg) was administered intraperitoneally (i.p.) daily from 0 to 14d. Doxorubicin (15mg/kg, i.p.) was given as a single dose on the 10th day. On the 14th day, all animals were sacrificed and oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) activities, and all mitochondrial complexes (I-IV) activities were evaluated along with histopathological studies of the heart.Doxorubicin-induced cardiotoxicity was confirmed by increased (p<0.05) MDA, decreased (p<0.05) GSH levels, SOD, and CAT activities, mitochondrial complexes (I-IV) activities in the heart tissue. NR (100mg/kg) showed cardioprotection as evident from significant decreased MDA (p<0.001) level, raised (p<0.001) GSH level, SOD and CAT activities and increased mitochondrial complexes I (p<0.01), II (p<0.001), III (p<0.001), and IV (p<0.05) activities. Further, Dox-induced cardiotoxicity was confirmed by histopathological studies. These obtained results indicated the protective role of NR against Dox-induced cardiac toxicity in rats.NR can be used in combination with Dox due to its high cardioprotective effect against Dox-induced cardiomyopathy.


PubMed | National Institute of Pharmaceutical Education and Research, Guwahati and Rajendra Memorial Research Institute of Medical Sciences
Type: Journal Article | Journal: Journal of biomolecular structure & dynamics | Year: 2016

Protein disulphide isomerase (PDI) is one of the key enzymes essential for the survival of Leishmania donovani in the host. Our study suggested that PDI is associated with the generation of Th1-type of cellular responses in treated Visceral leishmaniasis (VL) subjects. The stimulation of Peripheral blood mononuclear cells (PBMCs) with recombinant Protein Disulphide Isomerase upregulated the reactive oxygen species generation, Nitric oxide release, IL12 and IFN- production indicating its pivotal role in protective immune response. Further, a pre-stimulation of PBMCs with Protein disulphide isomerase induced a strong IFN- response through CD8+ T cells in treated VL subjects. These findings also supported through the evidence that this antigen was processed and presented by major histocompatibility complex class I (MHC-1) dependent pathway and had an immunoprophylactic potential which can induce CD8+ T cell protective immune response in MHC class I dependent manner against VL. To find out the possible epitopes that might be responsible for CD8+ T cell specific IFN- response, computational approach was adopted. Six novel promiscuous epitopes were predicted to be highly immunogenic and can be presented by 32 different HLA allele to CD8+ T cells. Further investigation will explore more about their immunological relevance and usefulness as vaccine candidates.


PubMed | National Institute of Pharmaceutical Education and Research, Guwahati and Rajendra Memorial Research Institute of Medical Sciences
Type: | Journal: Molecular immunology | Year: 2017

In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future.


PubMed | Bharati Vidyapeeth Deemed University, University of Kentucky, National Institute of Pharmaceutical Education and Research, Guwahati and Jamia Hamdard University
Type: Journal Article | Journal: Neurochemical research | Year: 2016

The present study was designed to investigate the neuroprotective effect of naringin (NR) alone as well as its combination with sertraline (SRT) against doxorubicin (DOX)-induced neurobehavioral and neurochemical anomalies. DOX (15mg/kg; i.p.) administration caused behavioral alterations, oxidative stress, neuroinflammation, mitochondrial dysfunction and monoamines alteration in male Wistar rats. NR (50 and 100mg/kg; i.p.) and SRT (5mg/kg; i.p.) treatment significantly attenuated DOX-induced anxiety and depressive-like behavior as evident from elevated plus maze(EPM) and modified forced swimming test(mFST), respectively. NR treatment significantly attenuated DOX-induced raised plasma corticosterone(CORT), tumor necrosis factor-alpha(TNF-) and interleukin-1 beta(IL-1) levels in the hippocampus (HC). Furthermore, we found that combination of NR and SRT regimen ameliorated DOX-induced behavioral anomalies through modulation of the 5-HT level and mitochondrial complexes protection pathway along with alleviation of oxidative stress in the HC region. Therefore, NR treatment alone or in combination with SRT could be beneficial against DOX-induced neurotoxicity.


PubMed | National Institute of Pharmaceutical Education and Research, Guwahati and Rajendra Memorial Research Institute of Medical Sciences
Type: | Journal: Cytokine | Year: 2017

Adenosine, an endogenous purine nucleoside is one such extracellular signaling molecule whose role in the regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is indeterminate. Here, we have evaluated the adenosine in the plasma of 20 visceral leishmaniasis (VL) patients during active disease and after successful treatment. We observed the elevated plasma adenosine during active VL disease (26.731.95M) and the level subsides as the treatment progresses and falls to the normal level after successful treatment (4.320.45M). We demonstrated a direct correlation between changes in the plasma adenosine level and the Th1/Th2 balance in VL patients and it was corroborated with in vitro experiment. Further, we delineated the molecular mechanism involved in the elevation of plasma adenosine during visceral leishmaniasis. Our results reveal that the elevated plasma adenosine level associated with pathogenicity and plays a critical role in skewing immune response from Th1 to Th2 type to influence the outcome of the disease.


PubMed | National Institute of Pharmaceutical Education and Research, Guwahati and Rajendra Memorial Research Institute of Medical Sciences
Type: | Journal: Cytokine | Year: 2016

Adenosine, an endogenous purine nucleoside is one such extracellular signalling molecule whose role in regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is not fully understood. Here, we investigated the relationship between Leishmania donovani infection and expression of A2B receptor on monocytes in VL patients in their pre and post treatment stage. We also investigated the molecular mechanisms influencing the interaction between immunopathogenicity and infection by exposing Leishmania donovani pulsed macrophages to Adenosine. A direct correlation of up-regulated A2B expression on monocytes with increased parasite load was also observed. Our results also suggested that A2B receptor activation is critically required for the stimulatory effect of adenosine on IL-10 production and suppression of nitric oxide release. The stimulatory effect of adenosine on Leishmania donovani induced IL-10 production required ERK1/2 activation and is p-38 MAPK independent.

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