Indian Institute of Toxicology Research
Indian Institute of Toxicology Research
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.
Tiwari P.,Indian Institute of Toxicology Research |
Gupta K.P.,Indian Institute of Toxicology Research
Toxicology and applied pharmacology | Year: 2014
We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203. Copyright © 2014 Elsevier Inc. All rights reserved.
Patnaik S.,Indian Institute of Toxicology Research |
Gupta K.C.,Indian Institute of Toxicology Research
Expert Opinion on Drug Delivery | Year: 2013
Introduction: Branched and linear polyethylenimines (PEIs) are cationic polymers that have been used to deliver nucleic acids both in vitro and in vivo. Owing to the high cationic charge, the branched polymers exhibit high transfection efficiency, and particularly PEI of molecular weight 25 kDa is considered as a gold standard in gene delivery. These polymers have been extensively studied and modified with different ligands so as to achieve the targeted delivery. Areas covered: The application of PEI in vivo promises to take the polymer-based vector to the next level wherein it can undergo clinical trials and subsequently could be used for delivery of therapeutics in humans. This review focuses on the various recent developments that have been made in the field of PEI-based delivery vectors for delivery of therapeutics in vivo. Expert opinion: The efficacy of PEI-based delivery vectors in vivo is significantly high and animal studies demonstrate that such systems have a potential in humans. However, we feel that though PEI is a promising vector, further studies involving PEI in animal models are needed so as to get a detailed toxicity profile of these vectors. Also, it is imperative that the vector reaches the specific organ causing little or no undesirable effects to other organs. © 2013 Informa UK, Ltd.
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.
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.