Haushila Prasad Pandey

Banaras Hindu University, Vārānasi, Uttar Pradesh, India

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Publications (33)63.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Deoxynivalenol (DON) is a Fusarium toxin that causes a variety of toxic effects with symptoms such as diarrhoea and low weight gain. To date, no review has addressed the toxicity of DON in relation to oxidative stress. The focus of this article is primarily intended to summarize the information associated with oxidative stress as a plausible mechanism for DON-induced toxicity. The present review shows that over the past two decades, several investigators have documented the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in oxidative stress as a result of DON treatment and have correlated them with various types of toxicity. The evidence for induction of an oxidative stress response resulting from DON exposure has been more focused on in vitro models and is relatively lacking in in vivo studies. Hence, more emphasis should be laid on in vivo investigations with doses that are commonly encountered in food products. Since DON is commonly found in food and feed, the cellular effects of this toxin in relation to oxidative stress, as well as effective measures to combat its toxicity, are important aspects to be considered for future studies.
    Food and Chemical Toxicology 07/2014; · 3.01 Impact Factor
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    ABSTRACT: Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [3H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential.
    Toxicology and Applied Pharmacology 06/2014; 279:186-197. · 3.98 Impact Factor
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    ABSTRACT: Cytochrome P4502E1 (CYP2E1), glutathione-S-transferase A4-4 (GSTA4-4), and inducible nitric oxide synthase (iNOS) are implicated in maneb- and paraquat-induced toxicity leading to various pathological conditions. The study aimed to investigate the role of CYP2E1 in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes (PMNs) and its crosstalk with iNOS-mediated nitrosative stress and GSTA4-4-linked protective effect, if any and their consequent links with the nuclear factor erythoid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression. Rats were treated with/without maneb and/or paraquat for 1, 2, and 3 weeks along with vehicle controls. Subsets of rats were also treated with diallyl sulfide (DAS) or aminoguanidine (AG) along with the respective controls. Maneb and paraquat augmented the reactive oxygen species (ROS), lipid peroxidation (LPO) and 4-hydroxy nonenal (4-HNE) contents, and superoxide dismutase (SOD) activity in the PMNs. However, maneb and paraquat attenuated the reduced glutathione (GSH) level and the expression/activity of total GST and GST-pi. Maneb and paraquat increased the expression/activity of CYP2E1, GSTA4-4, iNOS, Nrf2 and HO-1, and nitrite content. CYP2E1 inhibitor, DAS noticeably alleviated maneb- and paraquat-induced ROS, LPO, 4-HNE, SOD, Nrf2 and HO-1, GST, GSH, and GST-pi while iNOS, nitrite content and GSTA4-4 levels were unchanged. Conversely, AG, an iNOS inhibitor, attenuated maneb- and paraquat-directed changes in nitrite, LPO, iNOS but it did not alter ROS, GSH, SOD, GST, GST-pi, Nrf2, HO-1, CYP2E1, and GSTA4-4. The results demonstrate that CYP2E1 induces iNOS-independent free radical generation and subsequently modulates the Nrf2-dependent HO-1 and 4-HNE-mediated GST expression in maneb- and paraquat-treated PMNs.
    Molecular and Cellular Biochemistry 04/2014; · 2.33 Impact Factor
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    ABSTRACT: Deoxynivalenol (DON), a toxic fungal metabolite is stable under different processing conditions, however, its stability in aqueous medium at different temperatures and low pH (1-2) (present in gastrointestinal tract) has not been investigated. In the present study, DON standard was used to study the influence of temperature and pH on DON stability in aqueous medium, characterization of degraded product and the comparative toxicity profile of the degraded and parent compound. The results suggest that standard DON was unstable at 125-250°C showing 16-100% degradation whereas DON at pH (1-3) had 30-66% degradation, with concomitant increase in the formation of a degraded product. Further ESI-MS characterization of dominant precursor ion of HPLC eluate of DON degraded product was found to be m/z 279, resembling the known metabolite, DOM-1. The degraded product of DON was reconfirmed as DOM-1, by comparison with standard DOM-1 and both gave a similar λmax at 208 nm. Comparative studies of both standard DOM-1 and degraded product of DON showed no cytotoxicity up to 6400 ng/ml while significant cytotoxicity was observed for DON (400 ng/ml). Our results suggest that highly acidic environment (pH 1-2) could be responsible for de-epoxydation of DON leading to the formation of DOM-1.
    Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 11/2013;
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    ABSTRACT: Abstract Aim: Diabetes plays a major role in progression of renal failure. The risk-factor profile changes during the progression of chronic kidney disease (CKD) from mild/moderate to end-stage renal disease. The relationship between glycemic indices, blood pressure, body mass index (BMI) and age at diagnosis in Indians has been less investigated. We assessed association of these risk factors with CKD stages in Indian population. Methods: This study was carried out on patients (n = 162) who were diagnosed with CKD and normal control group (n = 155). For BMI, National Institutes for Health criteria were used to categorize the patients. Result: The mean age of CKD patients were significantly increased with the advancement of stage. BMI, systolic blood pressure (SBP), postprandial sugar level (PP), urea and creatinine were also significantly higher with elevated stages, whereas no differences were observed in diastolic blood pressure (DBP) and fasting blood sugar (FBS). The logistic regression study gave a significant result (p = 0.000) when we compared the group of CKD patients with established/prolonged postprandial blood sugar. It was independently associated with mild CKD [odds ratio (OR) = 5.213, 95% confidence interval (CI) = 2.06-13.21, p = 0.000], moderate CKD (OR = 7.724, 95% CI = 4.05-14.74, p = 0.000) and severe CKD (OR = 7.610, 95% CI = 4.03-14.36, p = 0.000). Conclusion: SBP and PP were the best predictors of prevalent nephropathy in this population, while DBP and FBS were found to be less effective. This may have implication for kidney disease risk stratification and protection.
    Renal Failure 09/2013; · 0.94 Impact Factor
  • XXXIII Annual Conference of Society of Toxicology (STOX), India for Synergy of Toxicology Research in SAARC Countries & National Symposia on “Phyto-remedial approaches against environmental pollutants for human and animal health, U.P. Pandit Deen Dayal Upadhyaya Pashu-Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan, (DUVASU) Mathura, India; 08/2013
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    ABSTRACT: Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47μg/ml as compared to the IC50 value of omeprazole (30.24μg/ml) confirming its anti-secretory activity.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 07/2013; · 2.97 Impact Factor
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    ABSTRACT: Nyctanthes arbortristis Linn (Oleaceae) is widely distributed in sub-Himalayan regions and southwards to Godavari, India commonly known as Harsingar and Night Jasmine. In continuation of our drug discovery program on Indian medicinal plants, we isolated arbortristoside-A (AT) and 7-O-trans-cinnamoyl-6β-hydroxyloganin (6-HL) from the seeds of N. arbortristis. AT and 6-HL exhibited anti ulcer activity in experimentally induced ulcer models including cold restraint stress (CRU), alcohol (AL), pylorus ligation-induced gastric ulcer (PL) models and they also showed ulcer healing effect in chronic acetic acid-induced ulcer model (AC).
    Phytomedicine: international journal of phytotherapy and phytopharmacology 06/2013; · 2.97 Impact Factor
  • National seminar on stress, development and adaptation; Biochemical basis and biotechnological approches, University of lucknow, Lucknow, India; 03/2013
  • “International conference on Advances in Free Radicals, Redox Signaling and Translational Antioxidant Research”, CSIR-Indian Institute of Toxicology Research, Lucknow, India; 01/2013
  • “International Conference on Chemistry and Materials: Prospects & Perspectives, Babasaheb Bhimrao Ambedkar University, Lucknow, India; 12/2012
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    ABSTRACT: Oxidative stress is one of the major players in the pathogenesis of maneb (MB) and paraquat (PQ)-induced disorders. N-acetyl cysteine (NAC), a glutathione (GSH) precursor and silymarin (SIL), a naturally occurring antioxidant, encounter oxidative stress-mediated cellular damage. The present study was aimed to investigate the effects of NAC and SIL against MB and/or PQ-induced hepatotoxicity in rats. The levels of hepatotoxicity markers - alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and total bilirubin, histological changes, oxidative stress indices, phase I and phase II xenobiotic metabolizing enzymes - cytochrome P450 (CYP) and glutathione S-transferase (GST) and pro-inflammatory molecules - inducible nitric oxide synthase (iNOS), tumor necrosis factor-α/TNF-α and interleukin-1β/IL-1β) were measured in animals treated with MB and/or PQ in the presence or absence of NAC and SIL. MB and/or PQ augmented ALT, AST, total bilirubin, lipid peroxidation and nitrite contents and catalytic activities of superoxide dismutase and glutathione peroxidase however, the GSH content was attenuated. NAC and SIL restored the above-mentioned alterations towards basal levels but the restorations were more pronounced in SIL treated groups. Similarly, MB and/or PQ-mediated histopathological symptoms and changes in the catalytic activities/expressions of CYP1A2, CYP2E1, iNOS, TNF-α, and IL-1β were alleviated by NAC and SIL. Conversely, MB and/or PQ-induced GSTA4-4 expression/activity was further increased by NAC/SIL and glutathione reductase activity was also increased. The results obtained thus suggest that NAC and SIL protect MB and/or PQ-induced hepatotoxicity by reducing oxidative stress, inflammation and by modulating xenobitic metabolizing machinery and SIL seems to be more effective.
    Chemico-biological interactions 11/2012; · 2.46 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate the immunomodulatory role of leishmanial excretory-secretory antigens (LESAs) released by in vitro cultured protozoan parasite Leishmania donovani promastigotes. A total of seventeen excretory-secretory proteins of relative molecular weights 11, 13, 16, 18, 21, 23, 26, 29, 33, 35, 42, 51, 54, 58, 64, 70 and 80kDa were identified. The proteins were divided into five fractions (F1-F5) along with the whole LESAs, these fractions were evaluated for their potential antigenicity to induce macrophage effector functions, lymphoproliferation and cytokines production capabilities. Two fractions, F1 (11, 13 and 16kDa) and F3 (26, 29 and 33kDa), were found to be highly immunogenic as they significantly induced NADPH oxidase and SOD activities as well as NOx, TNF-α, IFN-γ and IL-12 production in stimulated RAW 264.7 macrophages. Further, these antigens also induced significant proliferation of human peripheral blood mononuclear cells along with increased production of IFN-γ and IL-12. The results strongly suggest the potential role of LESAs in the modulation of macrophage effector functions and Th1 immune response that gives a hope to develop potent vaccine for visceral leishmaniasis.
    Experimental Parasitology 08/2012; 132(3):355-61. · 2.15 Impact Factor
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    ABSTRACT: Methylation of vertebrate DNA is one of the most important epigenetic alterations which have become a center of scientific attraction, especially because of its important role in the regulation of transcription, genomic imprinting, developmental process, and pathogenesis of various diseases. Currently, there are wide ranges of methods available to produce quantitative and qualitative information on genomic DNA methylation. The vast majority of these methods rely on the optimization of the efficient bisulfite treatment. However, all the available methods for bisulfite treatment suffer from major disadvantages, such as large amount of starting material, poor conversion efficiency as well as low recovery and integrity of DNA after bisulfite treatment. Here, we developed a simple, rapid, and convenient column-based bisulfite treatment method by improving the several critical steps, which leads to consistent C-to-U conversion rate 99-100 %, >75 % recovery of DNA after bisulfite treatment. In addition, it is commercially viable and requires very less amount (∼10 pg) of DNA.
    Applied biochemistry and biotechnology 08/2012; 168(4):797-804. · 1.94 Impact Factor
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    ABSTRACT: Vibrio cholerae uses quorum sensing communication system to interact with other bacteria and for gauzing environmental parameters. This organism dwells equally well in both human host and aquatic environments. Quorum sensing regulates multitude of activities and is one of the lucrative targets presently pursued for drug design in bacteria to encounter virulence. Histidine phosphotransfer protein LuxU and response regulator LuxO of V. cholerae are known to play important roles in biofilms and virulence machinery. In the present study, we used computational methods to model LuxU and LuxO and simulated the interactions of LuxO and LuxU. Since no structural details of the proteins were available, we employed homology modeling to construct the three-dimensional structures and then performed molecular dynamics simulations to study dynamic behavior of the LuxO and LuxU from V. cholerae. The modeled proteins were validated and subjected to molecular docking analyses. This allowed us to predict the binding modes of the proteins to elucidate probable sites of interference.
    Journal of biomolecular structure & dynamics 06/2012; 30(5):574-84. · 4.99 Impact Factor
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    ABSTRACT: In the 21st century, emerging area of systems biology is a whole-istic approach to understand biology by the crosstalk study between genome, Rnome and proteome of a cell. Here we describe a column based rapid method for the simultaneous extraction of nucleic acids, small RNAs and proteins from the same experimental sample (without fractionation) allowing for direct correlations between genomic, epi-genomic, transcriptomic and proteomic data, thus reducing inconsistent results and variability. Our method provides a rapid isolation of crucial biomolecules within one hour with the highest quality of isolated biomolecules. Further isolated DNA, RNA and miRNAs are suitable for all common downstream applications such as PCR, RT-PCR, reverse Northern blotting and Real time PCR. Similarly isolated protein is also suitable for SDS-PAGE and Western blot analysis. The buffers and reagents used in this method are optimized extensively to achieve the cost effective and reliable procedure to separate the functional biomolecules of the cell.
    Cell Biology International 05/2012; · 1.64 Impact Factor
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    ABSTRACT: Intracellular pathogenic protozoan infection like visceral leishmaniasis is considered in terms of the overall inflammatory response and the complex cellular interactions leading to formation of the activated macrophage. Analysis of the development of activation is facilitated when operationally defined stage of activation are characterized using a library of objective markers. There is a role of arginase in the immune response supporting its involvement in macrophage effector mechanism in vitro and in vivo. 5'-Nucleotidase a plasma membrane component has been cited as a biochemical correlate of macrophage function in an altered morphological and biochemical state of activation and stimulation. Depression in 5'-nucleotidase activity has been generally referred to as a characteristic marker of activated macrophages. Lysozyme or lysosomal enzymes are released into the endocytic or autophagic vacuole macrophage where they serve the purpose of intracellular digestion of engulfed or segregated materials. In the present study, we have studied levels of arginase and 5'-nucleotidase (marker for macrophage activation) in monocytes of active VL patients and healthy controls. Lysozyme a secretary product of macrophages was also measured in supernatants collected from monocytes of active VL patients and healthy controls. Elevated levels of 5'-nucleotidase were observed in supernatants of monocytes from active VL patients as compared to healthy controls. Low levels of arginase and lysozyme production by monocytes isolated from VL patients were observed as compared to healthy controls. Our studies suggest that low levels of arginase and elevated 5'-nucleotidase activity could be one of the mechanisms in the pathology of VL infection. Low lysozyme activity in patients may account for persistence of Leishmania parasites in VL infections.
    Journal of parasitic diseases 04/2012; 36(1):19-25.
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    ABSTRACT: An association between excessive zinc (Zn) accumulation in brain and incidences of Parkinson's disease (PD) has been shown in several epidemiological and experimental investigations. The involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and glutathione (GSH) in the pathogenesis of PD has also been proposed in a few studies. Despite the implicated role of oxidative stress in PD, the entire mechanism of Zn-induced dopaminergic neurodegeneration has not yet been clearly understood. The present study aimed to investigate the involvement of NADPH oxidase and GSH in Zn-induced dopaminergic neurodegeneration and also to assess its similarity with paraquat (PQ)-induced rat model of PD. Male Wistar rats were treated either with Zn (20 mg/kg; i.p.) or PQ (5 mg/kg; i.p.) in the presence and absence of NADPH oxidase inhibitor, apocynin (10 mg/kg; i.p.) and a GSH precursor, N-acetyl cysteine (NAC; 200 mg/kg; i.p.) either alone or in combination along with the respective controls. Apocynin and/or NAC pre-treatment significantly alleviated Zn- and PQ-induced changes in neurobehavioral deficits, number of dopaminergic neurons and contents of the striatal dopamine and its metabolites. Apocynin and/or NAC also mitigated Zn- and PQ-induced alterations in oxidative stress, NADPH oxidase activation and cytochrome c release, caspases-9 and -3 activation and CD11b expression. The results obtained thus suggest that Zn induces oxidative stress via the activation of NADPH oxidase and depletion of GSH, which in turn activate the apoptotic machinery leading to dopaminergic neurodegeneration similar to PQ.
    Brain research 02/2012; 1438:48-64. · 2.46 Impact Factor
  • XXXII Annual Meeting of Society of Toxicology (STOX), CSIR-Indian Institute of Toxicology Research, Lucknow, India; 01/2012
  • Journal of biomolecular structure & dynamics 01/2012; · 4.99 Impact Factor

Publication Stats

87 Citations
63.11 Total Impact Points

Institutions

  • 2008–2014
    • Banaras Hindu University
      • Department of Biochemistry
      Vārānasi, Uttar Pradesh, India
  • 2008–2013
    • Indian Institute of Toxicology Research
      • Division of Developmental Toxicology
      Lakhnau, Uttar Pradesh, India