Systems Toxicology & Health Risk Assessment

Preamble/Overview

Humans are exposed to many chemicals in the form of drugs but also through the environment. In order to understand the risk to human health of drug and chemical exposure, it is necessary to understand how these xenobiotics may affect normal cellular processes and so lead to toxicological consequence. The advent of high throughput genomic screens has led to the possibility of much greater breadth of understanding of the effect of xenobiotics in biological systems. Furthermore there has been interest in the possibility of using the output of these genomic assays as a signature of xenobiotic exposure, and thus as a test procedure for the recognition of toxicological hazard. Systems Toxicology and Health Risk Assessment aims to apply a system biology approach to describe and predict the effects of chemicals and other environmental stressors at different levels of biological organisation and identify key events leading to adverse health outcomes. The group aims to study the perturbation of biological systems by chemicals and stressors, monitoring changes in molecular expression and conventional toxicological parameters, iteratively integrating data to achieve a mechanistic understanding of the specific toxicity, and eventually develop and validate biomarkers for predicting these toxicological responses. The development of an integrated framework through the identification of toxicological pathways and data analysis tools is an integral part of the overall attempt to understand the adverse effects of chemicals and other stressors on human health and the environment. Particular focus will be placed on the development, assessment and application of methods for assessing the adverse effects of environmental chemicals. This will include the development and evaluation of Integrated Testing Strategies to describe all the toxicological interactions that occur within a living system under stress and use our knowledge of toxicogenomic responses in one species to predict the modes-of-action of similar agents in other species.

Objectives

  • Study the perturbation of biological systems by chemicals and stressors
  • Monitoring changes in molecular expression and conventional toxicological parameters and integrating data to achieve a mechanistic understanding of the specific toxicity
  • Develop and validate biomarkers for predicting the toxicological responses
  • Glimpses of Research:
    1. Agarwal S, Tiwari SK, Seth B, Yadav A, Singh A, Mudawal A, Chauhan LK, Gupta SK, Choubey V, Tripathi A, Kumar A, Ray RS, Shukla S, Parmar D, Chaturvedi RK, (2015). Activation of autophagic flux against xenoestrogen Bisphenol-A induced hippocampal neurodegeneration via AMPK/mTOR pathways. J Biol Chem, 290: 21163-84.
    2. Agrawal S, Dixit A, Singh A, Tripathi P, Singh D, Patel DK, Singh MP, (2015). Cyclosporine A and MnTMPyP alleviate α-synuclein expression and aggregation in cypermethrin-induced Parkinsonism. Mol Neurobiol, 52: 1619-28.
    3. Amar SK, Goyal S, Dubey D, Srivastav AK, Chopra D, Singh J, Shankar J, Chaturvedi RK, Ray RS, (2015). Benzophenone 1 induced photogenotoxicity and apoptosis via release of cytochrome c and Smac/DIABLO at environmental UV radiation. Toxicol Lett, 239: 182-93.
    4. Amar SK, Goyal S, Mujtaba SF, Dwivedi A, Kushwaha HN, Verma A, Chopra D, Chaturvedi RK, Ray RS, (2015). Role of type I & type II reactions in DNA damage and activation of caspase 3 via mitochondrial pathway induced by photosensitized benzophenone. Toxicol Lett, 2: 84-95.
    5. Awasthi P, Foiani M, Kumar A, (2015). ATM and ATR signaling at a glance. J Cell Sci, 128: 4255-62.
    6. Chauhan AK, Mittra N, Kumar V, Patel DK, Singh C, (2015). Inflammation and B-cell lymphoma-2 associated X protein regulate zinc-induced apoptotic degeneration of rat nigrostriatal dopaminergic neurons. Mol Neurobiol, (Epub; Oct 26), PMID: 26497033.
    7. Chopra D, Ray L, Dwivedi A, Tiwari SK, Singh J, Singh KP, Kushwaha HN, Jahan S, Pandey A, Gupta SK, Chaturvedi RK, Pant AB, Ray RS, Gupta KC, (2016). Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line. Biomaterials, 84: 25-41.
    8. Das M, Asthana S, Singh SP, Dixit S, Tripathi A, John TJ, (2015). Litchi fruit contains methylene cyclopropyl-glycine. Curr Sci, 109: 2195-97.
    9. Goyal S, Amar SK, Dubey D, Pal MK, Singh J, Verma A, Kushwaha HN, Ray RS, (2015). Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation. J Hazard Mater, 300: 415-25.
    10. Goyal S, Amar SK, Dwivedi A, Mujtaba SF, Kushwaha HN, Chopra D, Pal MK, Singh D, Chaturvedi RK, Ray RS, (2016). Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells. Toxicol Appl Pharmacol, 297: 12-21.
    11. Gupta SP, Kamal R, Mishra SK, Singh SK, Shukla R, Singh MP, (2015). Association of polymorphism in exon 29 of neuronal nitric oxide synthase gene with risk to Parkinson’s disease in Indian population. Mol Neurobiol, (Epub; June 17), PMID: 26081147.
    12. Kamal R, Kesavachandran C, Bihari V, Sathian B, Srivastava AK, (2015). Alterations in lung functions based on BMI and Body Fat % among obese Indian population at National Capital Region. Nepal J Epidemiol, 5: 470-79.
    13. Kamal R, Srivastava AK, Kesavachandran CN, (2015). Meta-Analysis approach to study the prevalence of chronic obstructive pulmonary disease among current, former and non-smokers. Toxicol Rep, 2: 1064-74.
    14. Kesavachandran CN, Bihari V, Pangtey BS, Kamal R, Singh A, Srivastava AK, (2015). Gender disparity in Lung Function Abnormalities among Population exposed to PM concentration in Ambient Air in National Capital Region, India. J Health Pollution, 9: 47-60.
    15. Kumar V, Gupta AK, Shukla RK, Tripathi VK, Jahan S, Pandey A, Srivastava A, Agrawal M, Yadav S, Khanna VK, Pant AB, (2015). Molecular Mechanism of Switching of TrkA/p75(NTR) Signaling in Monocrotophos Induced Neurotoxicity. Sci Rep, 5: 14038.
    16. Kumar V, Pandey A, Jahan S, Shukla RK, Kumar D, Srivastava A, Singh S, Rajpurohit CS, Yadav S, Khanna VK, Pant AB, (2016). Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis. Sci Rep, 6: 28142.
    17. Kumar V, Singh BK, Chauhan AK, Singh D, Patel DK and Singh C, (2015). Minocycline rescues from zinc-induced nigrostriatal dopaminergic neurodegeneration: biochemical and molecular interventions. Mol Neurobiol, 53: 2761-77.
    18. Maurya SK, Mishra J, Abbas S, Bandyopadhyay S, (2016) Cypermethrin stimulates GSK3β-dependent Aβ and p-tau proteins and cognitive-loss in young rats: Reduced HB-EGF signaling and downstream neuroinflammation as critical regulators. Mol Neurobiol, 53: 968-82.
    19. Shukla AK, Ratnasekhar Ch, Pragya P, Chaouhan HS, Patel DK, Chowdhuri DK, Mudiam MKR, (2016). Metabolomic analysis provides insights on paraquat induced Parkinson-like symptoms in Drosophila Melanogaster. Mol Neurobiol, 53: 254-69.
    20. Shukla RK, Gupta R, Srivastava P, Dhuriya YK, Singh A, Chandravanshi LP, Kumar A, Siddiqui MH, Parmar D, Pant AB, Khanna VK, (2016). Brain cholinergic alterations in rats subjected to repeated immobilization or forced swim stress on lambda-cyhalothrin exposure. Neurochem Int, 93: 51-63.
    21. Shukla S, Singh D, Kumar V, Chauhan AK, Singh S, Ahmad I, Pandey HP, Singh C, (2015). NADPH oxidase mediated maneb- and paraquat-induced oxidative stress in rat polymorphs: Crosstalk with mitochondrial dysfunction. Pestic Biochem Physiol, 123: 74-86.
    22. Singh A, Chandrasekharan Nair K, Kamal R, Bihari V, Gupta MK, Mudiam MK, Satyanarayana GN, Raj A, Haq I, Shukla NK, Khan AH, Srivastava AK, (2016). Assessing hazardous risks of indoor airborne polycyclic aromatic hydrocarbons in the kitchen and its association with lung function and urinary PAH metabolites in kitchen workers. Clin Chim Acta, 452: 204-13.
    23. Singh A, Kamal R, Mudium MKR, Gupta MK, Satyanarayana GNV, Bihari V, Shukla N, Khan AH, Kesavachandran CN, (2016). Heat and PAHs Emissions in Indoor Kitchen Air and Its Impact on Kidney Dysfunctions among Kitchen Workers in Lucknow, North India. PLoS One, (Epub; Feb 12), PMID: 26871707.
    24. Singh BK, Kumar V, Chauhan AK, Dwivedi A, Singh S, Kumar A, Singh D, Patel DK, Ray RS, Jain SK, Singh C, (2016). Neuronal Nitric Oxide Synthase Negatively Regulates Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration. Mol Neurobiol, (Epub; Mar 19), PMID: 26995406.
    25. Singh RD, Tiwari R, Khan H, Kumar A, Srivastava V, (2015). Arsenic exposure causes epigenetic dysregulation of IL-8 expression leading to proneoplastic changes in kidney cells. Toxicol Lett, 237: 1-10.
    26. Singh S, Srivastava A, Kumar V, Pandey A, Kumar D, Rajpurohit CS, Khanna VK, Yadav S, Pant AB, (2015). Stem Cells in Neurotoxicology/Developmental Neurotoxicology: Current Scenario and Future Prospects. Mol Neurobiol, (Epub; Dec 14), PMID: 26666665.
    27. Singhal NK, Agarwal S, Bhatnagar P, Tiwari MN, Tiwari SK, Srivastava G, Kumar P, Seth B, Patel DK, Chaturvedi RK and Singh MP, Gupta KC, (2015). Mechanism of nanotization-mediated improvement in the efficacy of caffeine against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced Parkinsonism. J Biomed Nanotechnol, 11: 2211-22.
    28. Srivastav AK, Mujtaba SF, Dwivedi A, Amar SK, Goyal S, Verma A, Kushwaha HN, Chaturvedi RK, Ray RS, (2016). Photosensitized rose Bengal-induced phototoxicity on human melanoma cell line under natural sunlight exposure. J Photochem Photobiol, 156: 87-99.
    29. Srivastava A, Kumar V, Pandey A, Jahan S, Kumar D, Rajpurohit CS, Singh S, Khanna VK, Pant AB, (2016). Adoptive autophagy activation: a much-needed remedy against chemical induced neurotoxicity/ developmental neurotoxicity. Mol Neurobiol, (Epub; Feb 18), PMID: 26887381.
    30. Syed F, Chandravanshi LP, Khanna VK and Soni I, (2016). Beta-cyfluthrin induced neurobehavioral impairments in adult rats. Chem Biol Interact, 243: 19-28.
    31. Tiwari SK, Seth B, Agarwal S, Yadav A, Karmakar M, Gupta SK, Choubey V, Sharma A, Chaturvedi RK, (2015). Ethosuximide induces hippocampal neurogenesis and reverses cognitive deficits in amyloid-β toxin induced Alzheimer’s rat model via PI3K/Akt/Wnt/β-catenin pathway. J Biol Chem, 290: 28540-58.
    Instrumentation and Facilities
    Medium throughput facility for receptor binding Microarray facility Neurobehavioral facility Protein Sequencer Tissue Culture facility

    Contact person:

    Dr. Devendra Parmar

    Chief Scientist
    Area Coordinator, Systems Toxicology & Health Risk Assessment Group
    CSIR-Indian Institute of Toxicology Research
    Vishvigyan Bhavan
    31, Mahatma Gandhi Marg
    Lucknow - 226 001, Uttar Pradesh, India
    Phone: +91-522-2217497
    Email: dparmar[at]iitr[dot]res[dot]in

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