Industrial Toxicology Research Centre is now named as Indian Institute of Toxicology Research , Lucknow, India. The institute is engaged in the field of Toxicology having its main campus in Lucknow city and the other Gheru campus, is located near village 'Gheru' at Lucknow-Kanpur highway.It is one of the constituent laboratory of CSIR India, which was established in 1965 with the motto of "Safety to Environment & Health and Service to Industry". The founder Director of the institute was Prof. Sibte Hasan Zaidi who died on 5 April 2008 at New York. He was the recipient of Padmashri and prestigious Sir Shanti Swaroop Bhatnagar award for scientific excellence. IITR conducts Dr. S.H. Zaidi Oration in his honour every year during its foundation day celebrations on 4 November.The institute is dedicated towards research in Fundamental and Applied Toxicology. Major thrust areas include Environmental toxicology, Ground and surface water pollution, Safety assessment of food & additives, Toxicity evaluation of substances for human use, Microbial contaminations, Bioremediation, Hazard identification and Toxicogenomics.The institute attracts students from all over India to pursue research. IITR offers Ph.D. programme in various areas, few to name are In vivo & In vitro Toxicology, Environmental Toxicology, Genetic Toxicology, Immunotoxicology, Neurotoxicology, Food Toxicology, Environmental Microbiology and Carcinogenesis.The institute also offers services for Toxicological and Analytical evaluation of chemicals / finished products to public and private sectors as per OECD, USEPA, BIS, ISO guidelines.IITR, dream of a visionary, became a reality in 1965 as Industrial Toxicology Research Centre located in Central Drug Research Institute, Lucknow. The founder Director, Prof. Sibte Hasan Zaidi, could foresee the need to address health related to work environment of the industrial workers in post independence era of rapid industrialization in our country. It was advocated that the adverse effects of chemicals on health and environment will make an adverse impact on overall development of the country. Hence, studies were needed to develop strategies for sustainable industrial development. ITRC gained national importance by addressing the health problems of our industrial work force in a growing economy. Pioneering studies carried out during the formative years were directly linked to miners' health especially to respiratory ailments.Like a unique organism, the institute adapted and evolved to grow from strength to strength with addition of new activities and expertise. Today, research in Toxicology is at the crossroad of transformation from classical studies of animal experimentation and histological observations of animal tissues in late sixties to state of the art omic technologies in interdisciplinary area of biology. The concept of biomarkers, alternate to animal models, mathematical modelling and predictive toxicology are to name a few to make toxicological research intrinsic in protection of human health and environment. ITRC was rechristened as the Indian Institute of Toxicology Research in 2008 to empower research activities in new frontiers of toxicology considering the paradigm shifts in our understanding of human and environmental health. In the new millennium, the institute is poised to make an impact in understanding the mode of action of new chemical entities, engineered nanomaterials and genetically modified products on living systems for safe use of new technologies and sustainable development.IITR website endeavours to provide a reflection of our mission in the new millennium. Wikipedia.
Chaturvedi R.K.,Indian Institute of Toxicology Research |
Chaturvedi R.K.,Academy of Scientific and Innovative Research AcSIR |
Beal M.F.,Cornell University
Free Radical Biology and Medicine | Year: 2013
Neurodegenerative disorders are debilitating diseases of the brain, characterized by behavioral, motor and cognitive impairments. Ample evidence underpins mitochondrial dysfunction as a central causal factor in the pathogenesis of neurodegenerative disorders including Parkinson's disease, Huntington's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Friedreich's ataxia and Charcot-Marie-Tooth disease. In this review, we discuss the role of mitochondrial dysfunction such as bioenergetics defects, mitochondrial DNA mutations, gene mutations, altered mitochondrial dynamics (mitochondrial fusion/ fission, morphology, size, transport/trafficking, and movement), impaired transcription and the association of mutated proteins with mitochondria in these diseases. We highlight the therapeutic role of mitochondrial bioenergetic agents in toxin and in cellular and genetic animal models of neurodegen-erative disorders. We also discuss clinical trials of bioenergetics agents in neurodegenerative disorders. Lastly, we shed light on PGC-1α, TORC-1, AMP kinase, Nrf2-ARE, and Sirtuins as novel therapeutic targets for neurodegenerative disorders. © 2013 Elsevier Inc. All rights reserved.
Chaturvedi R.K.,Indian Institute of Toxicology Research |
Beal M.F.,Cornell University
Molecular and Cellular Neuroscience | Year: 2013
Substantial evidence from both genetic and toxin induced animal and cellular models and postmortem human brain tissue indicates that mitochondrial dysfunction plays a central role in pathophysiology of the neurodegenerative disorders including Parkinson's disease (PD), and Huntington's disease (HD). This review discusses the emerging understanding of the role of mitochondrial dysfunction including bioenergetics defects, mitochondrial DNA mutations, familial nuclear DNA mutations, altered mitochondrial fusion/fission and morphology, mitochondrial transport/trafficking, altered transcription and increased interaction of pathogenic proteins with mitochondria in the pathogenesis of PD and HD. This review recapitulates some of the key therapeutic strategies applied to surmount mitochondrial dysfunction in these debilitating disorders. We discuss the therapeutic role of mitochondrial bioenergetic agents such as creatine, Coenzyme-Q10, mitochondrial targeted antioxidants and peptides, the SIRT1 activator resveratrol, and the pan-PPAR agonist bezafibrate in toxin and genetic cellular and animal models of PD and HD. We also summarize the phase II-III clinical trials conducted using some of these agents. Lastly, we discuss PGC-1α, TORC and Sirtuins as potential therapeutic targets for mitochondrial dysfunction in neurodegenerative disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. © 2012 Elsevier Inc.
Dhawan A.,Indian Institute of Toxicology Research |
Sharma V.,Indian Institute of Toxicology Research
Analytical and Bioanalytical Chemistry | Year: 2010
The increasing use of nanomaterials in consumer and industrial products has aroused global concern regarding their fate in biological systems, resulting in a demand for parallel risk assessment. A number of studies on the effects of nanoparticles in in vitro and in vivo systems have been published. However, there is still a need for further studies that conclusively establish their safety/toxicity, due to the many experimental challenges and issues encountered when assessing the toxicity of nanomaterials. Most of the methods used for toxicity assessment were designed and standardized with chemical toxicology in mind. However, nanoparticles display several unique physicochemical properties that can interfere with or pose challenges to classical toxicity assays. Recently, some new methods and modified versions of pre-existing methods have been developed for assessing the toxicity of nanomaterials. This review is an attempt to highlight some important methods employed in nanomaterial toxicology and to provide a critical analysis of the major issues/challenges faced in this emerging field. [Figure not available: see fulltext.] © 2010 Springer-Verlag.
Kapoor R.,Indian Institute of Toxicology Research |
Kakkar P.,Indian Institute of Toxicology Research
PLoS ONE | Year: 2012
Apoptosis is an early event of liver damage in diabetes and oxidative stress has been linked to accelerate the apoptosis in hepatocytes. Therefore, the compounds that can scavenge ROS may confer regulatory effects on high-glucose induced apoptosis. In the present study, primary rat hepatocytes were exposed to high concentration (40 mM) of glucose. At this concentration decreased cell viability and enhanced ROS generation was observed. Depleted antioxidant status of hepatocytes under high glucose stress was also observed as evident from transcriptional level and activities of antioxidant enzymes. Further, mitochondrial depolarisation was accompanied by the loss of mitochondrial integrity and altered expression of Bax and Bcl-2. Increased translocation of apoptotic proteins like AIF (Apoptosis inducing factor) & Endo-G (endonuclease-G) from its resident place mitochondria to nucleus was also observed. Cyt-c residing in the inter-membrane space of mitochondria also translocated to cytoplasm. These apoptotic proteins initiated caspase activation, DNA fragmentation, chromatin condensation, increased apoptotic DNA content in glucose treated hepatocytes, suggesting mitochondria mediated apoptotic mode of cell death. Morin, a dietary flavonoid from Psidium guajava was effective in increasing the cell viability and decreasing the ROS level. It maintained mitochondrial integrity, inhibited release of apoptotic proteins from mitochondria, prevented DNA fragmentation, chromatin condensation and hypodiploid DNA upon exposure to high glucose. This study confirms the capacity of dietary flavonoid Morin in regulating apoptosis induced by high glucose via mitochondrial mediated pathway through intervention of oxidative stress. © 2012 Kapoor, Kakkar.
Mudiam M.K.R.,Indian Institute of Toxicology Research |
Ratnasekhar C.,Indian Institute of Toxicology Research
Journal of Chromatography A | Year: 2013
A rapid and economical method for the simultaneous determination of 20 amino acids in complex biological and food matrices (hair, urine and soybean seed samples) has been developed using ultrasound assisted dispersive liquid-liquid micro extraction (UA-DLLME). The method involves simultaneous derivatization and extraction followed by gas chromatography-mass spectrometric (GC-MS) analysis of amino acids. The parameters of UA-DLLME were optimized with the aid of design of experiments approach. The procedure involves the rapid injection of mixture of acetonitrile (disperser solvent), trichloroethylene (TCE) (extraction solvent) and ethylchloroformate (derivatization reagent) into the aqueous phase of sample extract containing pyridine. The Plackett-Burman design has indicated that, the factors such as volume of disperser and extraction solvents and pH were found to be significantly affects the extraction efficiency of the method. The optimum conditions of these factors based on central composite design were found to be 250μL of acetonitrile, 80μL of TCE and pH of 10. The limit of detection and limit of quantification were found to be in the range of 0.36-3.68μgL-1 and 1.26-12.01μgL-1 respectively. This is the first application of DLLME for the analysis of amino acids in any matrices. The advantages like (i) in situ derivatization and extraction of amino acids without any prior lyophilization and cleanup of sample, (ii) low consumption of extraction solvent, (iii) fast and simple, (iv) cost-effective and (iv) good repeatability make the method amenable for the routine analysis of amino acids in clinical, toxicological, nutritional and quality control laboratories. © 2013 Elsevier B.V.
Mudiam M.K.,Indian Institute of Toxicology Research
Analytical and bioanalytical chemistry | Year: 2011
A simple and rapid analytical method based on in-matrix ethyl chloroformate (ECF) derivatization has been developed for the quantitative determination of bisphenol-A (BPA) in milk and water samples. The samples containing BPA were derivatised with ECF in the presence of pyridine for 20 s at room temperature, and the non-polar derivative thus formed was extracted using polydimethylsiloxane solid-phase microextraction (SPME) fibres with thicknesses of 100 μm followed by analysis using gas chromatography-mass spectrometry. Three alkyl chloroformates (methyl, ethyl and isobutyl chloroformate) were tested for optimum derivatisation yields, and ECF has been found to be optimum for the derivatisation of BPA. Several parameters such as amount of ECF, pyridine and reaction time as well as SPME parameters were studied and optimised in the present work. The limit of detection for BPA in milk and water samples was found to be 0.1 and 0.01 μg L(-1), respectively, with a signal-to-noise ratio of 3:1. The limit of quantitation for BPA in milk and water was found to be 0.38 and 0.052 μg L(-1), respectively, with a signal-to-noise ratio of 10:1. In conclusion, the method developed was found to be rapid, reliable and cost-effective in comparison to silylation and highly suitable for the routine analysis of BPA by various food and environmental laboratories.
Mahmood Z.,Indian Institute of Toxicology Research |
Shukla Y.,Indian Institute of Toxicology Research
Experimental Cell Research | Year: 2010
Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be involved in apoptosis signaling, independent of p53 tumor-supressor gene. Selective triggering of DR-mediated apoptosis in cancer cells is a novel approach in cancer therapy. So far, the best characterized DRs are CD95 (Fas/Apo1), TNF-related apoptosis-inducing ligand receptor (TRAILR) and tumor necrosis factor receptor (TNFR). Among these, TRAILR is emerging as most promising agent for cancer therapy, because it induces apoptosis in a variety of tumor and transformed cells without any toxicity to normal cells. TRAIL treatment in combination with chemotherapy or radiotherapy enhances TRAIL sensitivity or reverses TRAIL resistance by regulating downstream effectors. This review covers the current knowledge about the DRs, summarizes main signaling in DRs and also summarizes the preclinical approaches of these DRs in cancer therapy. © 2009 Elsevier Inc. All rights reserved.
Shukla Y.,Indian Institute of Toxicology Research |
Singh R.,Indian Institute of Toxicology Research
Annals of the New York Academy of Sciences | Year: 2011
The use of novel and improved chemopreventive and chemotherapeutic agents for the prevention and treatment of cancer is on the rise. Natural products have always afforded a rich source of such agents. Epidemiological evidence suggests that a higher flavonoid intake is associated with low cancer risk. Accumulating data clearly indicate that the induction of apoptosis is an important component in the chemoprevention of cancer by naturally occurring dietary agents. Resveratrol, a naturally occurring polyphenol, demonstrates pleiotropic health benefits, including antioxidant, anti-inflammatory, antiaging, cardioprotective, and neuroprotective activities. Because of these properties and their wide distribution throughout the plant kingdom, resveratrol is envisioned as a potential chemopreventive/curative agent. Currently, a number of preclinical findings from our lab and elsewhere suggest resveratrol to be a promising natural weapon in the war against cancer. Remarkable progress in elucidating the molecular mechanisms underlying the anticancer properties of resveratrol has been achieved. Here, we focus on some of the myriad pathways that resveratrol targets to exert its chemopreventive role and advocate that resveratrol holds tremendous potential as an efficient anticancer drug of the future. © 2011 New York Academy of Sciences.
Singh M.,Indian Institute of Toxicology Research
Journal of biomedical nanotechnology | Year: 2011
Anti-cancer potential of polymer based nanoparticle of EGCG and TF alone and in combination with anti-cancer drug cisplatin have been studied in human cancer lines: A549 (lung carcinoma), HeLa (cervical carcinoma) and THP-1 (acute monocytic leukemia) using cell proliferation assay and cell cycle analysis. Encapsulated polyphenols retained biological effectiveness with over 20-fold dose advantage than EGCG/TF in exerting anti-cancer effects and also enhanced the potential of a widely used anti-cancer drug cisplatin. Subsequently, encapsulated polyphenols alone or in combination with cisplatin were more effective in inhibiting cell proliferation, metastasis, angiogenesis and apoptosis biomarkers. Collectively, our observations reveal that nanoparticle-mediated delivery of phytochemicals could serve as a basis for enhancing bioavailability and limiting the unwanted toxicity of chemotherapeutic agents.
Shukla A.K.,Indian Institute of Toxicology Research
Neurobiology of aging | Year: 2014
Parkinson's disease (PD) is a prevalent and devastating neurodegenerative disorder having limited cure options and strong association with the loss of dopaminergic neurons in the substantia nigra region of the mid brain. Etiology of PD includes both genetic and environmental factors. Paraquat (PQ), a widely used herbicide, is known to be associated with pathogenesis of PD. We report that a mutation in Drosophila methuselah (mth(1)), which is associated with aging, has a role in preventing dopaminergic neuronal cell death in PQ-exposed organism. Exposed mth(1) flies exhibit significant resistance against PQ-induced Parkinson's phenotypes and behavior in terms of oxidative stress, dopaminergic neuronal degeneration, locomotor performance, dopamine content, phosphorylated JNK, pFOXO, Hid, and cleaved caspase-3 levels. Conversely, over-expression of mth in dopaminergic neurons makes the exposed organism more vulnerable to oxidative stress, neuronal cell death, and behavioral deficit. The study suggests that lesser activation of JNK-mediated apoptosis in dopaminergic neurons of exposed mth(1) flies protects the organism from PQ-induced damage, which may be causally linked to a common mechanism for PQ-induced neurodegeneration. Copyright © 2014 Elsevier Inc. All rights reserved.