Prof. Suhel Parvez, Jamia Hamdard | Jamia Hamdard, New Delhi (original) (raw)

Papers by Prof. Suhel Parvez, Jamia Hamdard

Environmental toxicology, Jan 9, 2015

Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing ... more Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing of polycarbonate plastics and epoxy resins. BPA and other endocrine disrupting chemicals (EDCs) act via multiple mechanisms including interference with mitochondrial functions. Mitochondria are the hub of cellular energy pool and hence are the target of many EDCs. We studied perturbation of activities of mitochondrial enzymes by BPA and its possible role in hepatotoxicity in Wistar rats. Rats were exposed to BPA (150 mg/kg, 250 mg/kg, 500 mg/kg per os, for 14 days) and activities of enzymes of mitochondrial electron transport chain (ETC) were measured. Besides, other biochemical parameters such as superoxide generation, protein oxidation, and lipid peroxidation (LPO) were also measured. Our results indicated a significant decrease in the activities of enzymes of mitochondrial ETC complexes, i.e., complex I, II, III, IV, and V along with significant increase in LPO and protein oxidation. ...

Ecological Indicators, 2015

ABSTRACT

Receptor-mediated Ca 2+ release from the endoplasmic reticulum (ER) is often followed by Ca 2+ en... more Receptor-mediated Ca 2+ release from the endoplasmic reticulum (ER) is often followed by Ca 2+ entry through Ca 2+-release-activated Ca 2+ (CRAC) channels in the plasma membrane [1-5]. RNAi screens have identified STIM1 as the putative ER Ca 2+ sensor [6-8] and CRACM1 (Orai1; [9-11]) as the putative store-operated Ca 2+ channel. Overexpression of both proteins is required to reconstitute CRAC currents (I CRAC ; [11-14]). We show here that CRACM1 forms multimeric assemblies that bind STIM1 and that acidic residues in the transmembrane (TM) and extracellular domains of CRACM1 contribute to the ionic selectivity of the CRAC-channel pore. Replacement of the conserved glutamate in position 106 of the first TM domain of CRACM1 with glutamine (E106Q) acts as a dominantnegative protein, and substitution with aspartate (E106D) enhances Na + , Ba 2+ , and Sr 2+ permeation relative to Ca 2+. Mutating E190Q in TM3 also affects channel selectivity, suggesting that glutamate residues in both TM1 and TM3 face the lumen of the pore. Furthermore, mutating a putative Ca 2+ binding site in the first extracellular loop of CRACM1 (D110/112A) enhances monovalent cation permeation, suggesting that these residues too contribute to the coordination of Ca 2+ ions to the pore. Our data provide unequivocal evidence that CRACM1 multimers form the Ca 2+-selective CRAC-channel pore.

Neuroscience, Jan 6, 2012

Valproic acid (VPA), a branched short-chain fatty acid, is generally used as an antiepileptic dru... more Valproic acid (VPA), a branched short-chain fatty acid, is generally used as an antiepileptic drug and a mood stabilizer. VPA is a relatively safe drug, but its use in higher concentrations is associated with idiosyncratic neurotoxicity. Investigations involving cerebral cortex and cerebellum can shed light on whether neurotoxicity induced by branched chain fatty acids like VPA is mediated by oxidative stress. The aim of our investigation was to evaluate the neurotoxic potential of VPA by using preparation of cerebral cortex and cerebellum of young rats as an in vitro model. Oxidative stress indexes such as lipid peroxidation (LPO) and protein carbonyl (PC) formation were evaluated to visualize whether the first line of defence was breached. The levels of oxidative stress markers, LPO and PC were significantly elevated. Non-enzymatic antioxidants' effect was also demonstrated as a significant depletion in reduced glutathione (GSH) and non-protein thiol activity (NP-SH), but ther...

Toxicology Mechanisms and Methods, 2015

Nanotechnology has emerged as a field of scientific innovation which has opened up a plethora of ... more Nanotechnology has emerged as a field of scientific innovation which has opened up a plethora of concerns for the potential impact on human and environment. Various toxicological studies have confirmed that nanoparticles (NPs) can be potentially hazardous because of their unique small size and physico-chemical properties. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilization and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system. Mitochondria is an important origin for generation of energy as well as free radicals and these free radicals can lead to mitochondrial damage and finally lead to apoptosis. The objective of our study was to elucidate the potential neurotoxic effect of TNPs in anatase form. Oxidative stress was determined by measuring lipid peroxidation and protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. Mitochondrial complexes were also modulated from the exposure to TNPs. The present study indicates that nanosize TNPs may pose a health risk to mitochondrial brain with the generation of reactive oxygen species, and thus NPs should be carefully used.

Journal of Trace Elements in Medicine and Biology, 2015

Cadmium (Cd) is a soft, malleable bluish-white metal with low melting point, a ubiquitous heavy m... more Cadmium (Cd) is a soft, malleable bluish-white metal with low melting point, a ubiquitous heavy metal and an environmental pollutant, found in soil, water and air. The presence of Cd in the components of the environment such as air, soil and groundwater is to a large part due to human activity, and the general population is exposed mainly by contaminated drinking water or food. Manganese (Mn) is a component in many enzymes, which play an important role in counteracting oxidative stress. In vitro experiments have revealed the ability of Mn to scavenge oxygen free radicals generated in differently mediated lipid peroxidation (LPO) conditions. The aim of the present study was to investigate the in vivo preventive effect of Mn 2+ pre-treatment on acute Cd-intoxication with regard to oxidative stress biomarker and antioxidant defense system in liver of Swiss albino mice. On exposure to Cd a significant increase in LPO levels, decrease in thiol content and induction in glutathione metabolizing enzyme were observed. Mn pre-treatment attenuated the modulation caused in the above-mentioned parameters due to acute Cd exposure in mice. In conclusion, the results from this study demonstrate that the protective effect of Mn in Cd-induced systemic toxicity in mice. Further investigations are required on the relation between Mn accumulation and resistance to oxidative stress and on the factors influencing Mn/Cd transport in rodents are needed to elucidate the molecular basis of this protective effect.

Biological Trace Element Research, 2011

Cadmium (Cd) is a toxic heavy metal commonly found in industrial workplaces, a food contaminant a... more Cadmium (Cd) is a toxic heavy metal commonly found in industrial workplaces, a food contaminant and a major constituent of cigarette smoke. Most of the organs are susceptible to Cd-induced toxicity, including brain. Postnuclear supernatant (PNS) has been accepted as an in vitro model for assessing xenobiotic induced toxicity. The goal of the present study was to validate PNS as an in vitro model for investigating the effect of Cd-induced neurotoxicity. Neurotoxic induction by Cd was established in a dosedependent manner in PNS in vitro. Enzymatic and nonenzymatic antioxidants were used as biomarkers of exposure. Antioxidant enzymatic activity was measured as a significant increase in activities of catalase, superoxide dismutase, and glutathione S-transferase. On exposure to Cd, a significant increase in acetylcholinesterase and decrease in sodium-potassium ATPase activity was also observed. Non-enzymatic effect was also demonstrated as a significant elevation in reduced glutathione and non-protein thiol activity, but there was no significant increase or decrease in the concentrations of protein thiol. In accordance with the toxicity of Cd towards the studied brain structure, Cd-induced oxidative stress has been a focus of toxicological research as a possible mechanism of neurotoxicity. Our results suggest that PNS preparations can be used as a model for future investigation of xenobioticinduced neurotoxicity under in vitro conditions.

Protoplasma, 2014

Valproic acid (VPA) is ubiquitously used as a major drug in the intervention of epilepsy and in t... more Valproic acid (VPA) is ubiquitously used as a major drug in the intervention of epilepsy and in the control of several kinds of seizures. Cellular toxicities are the serious dose-limiting side effects of VPA when applied in the treatment of diseases. Oxidative stress has been proven to be involved in VPA-induced toxicity. Accumulating evidence intimates that oxidative stress caused by free radicals and in kidney cells contributes to the pathogenesis of VPA-induced nephrotoxicity. The pathogenesis of these forms of VPA nephrotoxicity is still not clear. The aim of our investigation was to evaluate the nephrotoxic potential of VPA and protective effects of quercetin (QR) against VPA-induced nephrotoxicity by using rat kidney tissue preparation as an in vitro model. Oxidative stress indexes such as lipid peroxidation (LPO) and protein carbonyl (PC) content were appraised. The levels of oxidative stress markers, LPO, and PC were significantly elevated. Nonenzymatic antioxidants effect was also demonstrated as a significant increase in reduced glutathione (GSH) and nonprotein thiol level (NP-SH). VPA exposure altered the activities of glutathione metabolizing enzymes such as glutathione-S-transferase, glutathione peroxidase, and glutathione reductase. Pre-treatment with QR could reverse the VPA-induced effects in kidney tissue preparation of rat. Based on reno-protective and antioxidant action of QR, we suggest that this flavonoid compound could be considered as a potential safe and effective approach in attenuating the adverse effect of VPA-induced nephrotoxicity.

Biological Trace Element Research, 2003

Effect of the low level of copper exposure on nonenzymatic antioxidants was studied in a freshwat... more Effect of the low level of copper exposure on nonenzymatic antioxidants was studied in a freshwater fish Channa punctatus (Bloch.). Fish were exposed to cupric chloride at the concentration of 10 ppb for 4 wk (28 d) in a static culture condition. Copper significantly (p < 0.001) increased the serum ceruloplasmin level and total iron-binding capacity. A significant (p < 0.05) increase in reduced glutathione level was recorded in all of the tissues. With regard to nonprotein thiols, copper decreased their level in the liver, but increased it in the gill. The protein-bound thiols remained unaltered except for an increase in the liver. Metallothionein (MT) induction was observed in liver only. Copper exposure had no significant effect on the ascorbic acid level and induced no lipid peroxidation over control values. It is suggested that by modulating the ceruloplasmin level, copper indirectly protects the fish, as it facilitates conversion of pro-oxidant iron to nonoxidant iron. It also induces an array of antioxidants that may be beneficial to fish in the case of oxidative stress resulting from chemical pollutants.

Toxicology, 2006

Natural antioxidants like catechin are now known to have a modulatory role on physiological funct... more Natural antioxidants like catechin are now known to have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from toxic metabolic actions of xenobiotics. Reactive oxygen intermediates have been demonstrated to play an etiological role in anticancer drug-induced toxicity. This study was performed to explore the modulatory and protective effect of catechin on the toxicity of an anticancer drug, tamoxifen (TAM) with special reference to protection against disruption of glutathione metabolizing and antioxidant enzymes. TAM treatment resulted in a significant increase in the lipid peroxidation (LPO), H 2 O 2 generation and protein carbonyl (PC) contents in the liver and kidney as compared to controls while catechin + TAM-treated group showed significant decrease in LPO levels, H 2 O 2 generation and PC contents in liver and kidney when compared with TAM-treated group. Non-enzymatic antioxidants like reduced glutathione (GSH) and low molecular antioxidants like ascorbic acid (AsA) also showed normalcy due to exogenous catechin administration. Catechin pre-treatment showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione metabolizing enzymes, viz., glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant enzymes such as, glucose-6-phosphate dehydrogenase (G6-PD), catalase (CAT) and superoxide dismutase (SOD) in both liver and kidney when compared to TAM-treated animals. The results of the study show that catechin supplementation might be helpful in abrogation of TAM toxicity during chemotherapy. Additionally, it makes it a prophylactic and preventive agent of anticancer drug-induced oxidative stress.

Toxicology, 2000

Spontaneous, so-called 'conformational' diseases, specially of the neurodegenerative type like Al... more Spontaneous, so-called 'conformational' diseases, specially of the neurodegenerative type like Alzheimer's, are linked to certain protein types which have the normal amino-acid sequence but are misfolded and accumulate due to resistance to proteolysis. In the case of prion diseases, the 'protein only' hypothesis assumes that the misconformation of a native protein could be initiated upon interaction with a sister-protein already in the misfolded state. There is an alternative to this sister protein contamination scheme, which assumes that the misconformation is acquired upon protein synthesis, that is de novo. Misfoldling and resistance to proteolysis could result from defects responsible for shortage or inactivity of the cellular factors in charge of protein folding and degradation. The defects could have a genetic origin (the gene of the faulty factor involved could have been mutated, or control and regulation of its expression could have been altered, etc.). Alternatively, the cell's actual biosynthetic and/or proteolytic resources could have become overloaded and unavailable, due to unscheduled mass-production of proteins resulting from unscheduled cell growth or proliferation, cell stress, etc. Xenobiotics, active for instance as endocrine proliferators, stressors, or inducing copious, unscheduled gene expression, etc. could give rise to shortage of cellular factors necessary for the production of native proteins and for proteolysis. Alternatively, xenobiotics could alter expression or activity of some of these factors. In both cases, the xenobiotic could be a 'conformational toxicant' by inducing misfolding of selected proteins. The xenobiotic could trigger some conformational disease if it targets a specific protein and tissue.

The FASEB Journal, 2006

The dopamine-D2-agonist pramipexole (PPX) was tested for blocking mitochondrial permeability tran... more The dopamine-D2-agonist pramipexole (PPX) was tested for blocking mitochondrial permeability transition (PT) in order to give a possible explanation for its neuroprotective effect seen in PPX-treated Parkinson's disease patients. Patch-clamp techniques for studying singlechannel currents in the inner mitochondrial membrane and large-amplitude swelling of energized mitochondria were used to study PPX action on the permeability transition pore (PTP), a key player in the mitochondrial route of the apoptotic cascade. Identity of the PTP was proven by measuring the concentration-response relation for cyclosporin A-blockade (IC 50 =26 nM). PPX inhibits the PTP reversibly with an IC 50 of 500 nM, which is close to the values determined earlier as plasma concentrations after PPX medication in patients. Interaction of PPX with the PTP is further supported by demonstrating that it abolished Ca 2+-triggered swelling in functionally intact mitochondria. Blockade of the PTP by PPX was attenuated by increasing concentrations of inorganic phosphate and by acidification. We suggest that PPX could exert part of its neuroprotective effect by inhibition of the PTP and thus, probably, blocking of the mitochondrial pathway of the apoptosis cascade.