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Repeated short-term stress synergizes the ROS signalling through up regulation of NFkB and iNOS expression induced due to combined exposure of trichloroethylene and UVB rays

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Abstract

Restraint stress is known to catalyse the pathogenesis of the variety of chronic inflammatory disorders. The present study was designed to evaluate the effect of repeated short-term stress (RRS) on cellular transduction apart from oxidative burden and early tumour promotional biomarkers induced due to combined exposure of trichloroethylene (TCE) and Ultra-violet radiation (UVB). RRS leads to the increase in the expression of the stress responsive cellular transduction elements NFkB-p65 and activity of iNOS in the epidermal tissues of mice after toxicant exposure. RRS augments the steep depletion of the cellular antioxidant machinery which was evidenced by the marked depletion in GSH (Glutathione and GSH dependant enzymes), superoxide dismutase and catalase activity that were observed at significance level of P < 0.001 with increase in lipid peroxidation, H2O2 and xanthine oxidase activity (P < 0.001) in the stressed animals and down regulation of DT-diaphorase activity (P < 0.001). Since, the induction of NFkB-p65 and inducible nitric oxide synthase expression mediated can lead to the hyperproliferation, we estimated a significant increment (P < 0.001) in the synthesis of polyamines in mice skin evidenced here by the ornithine decarboxylase which is the early marker of tumour promotion and further evaluated PCNA expression. All these findings cues towards the synergising ability of repeated short-term stress in the toxic response of TCE and UVB radiation.

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Abbreviations

RRS:

Repeated restraint stress

TCE:

Trichloroethylene

UVB:

Ultra-violet radiation

ODC:

Ornithine decarboxylase

NFkB-p65:

Nuclear factor kappa B

iNOS:

Inducible nitric oxide synthase

GSH:

Glutathione

GR:

Glutathione reductase

GPx:

Glutathione peroxidase

SOD:

Superoxide dismutase

CAT:

Catalase

LPO:

Lipid peroxidation

H2O2 :

Hydrogen peroxide

XO:

Xanthine oxidase

PCNA:

Proliferating cell nuclear antigen

MPO:

Myeloperoxidase

NADPH:

Nicotinamide adenine dinucleotide phosphate

CDNB:

1-Chloro-2,4-dinitrobenzene

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Acknowledgement

Author Sarwat Sultana is thankful to University Grants Commission, Govt. of India, New Delhi, for providing Meritorious Research Fellowship to her student Farrah Ali.

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  1. Section of Molecular Carcinogenesis and Chemoprevention Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Farrah Ali & Sarwat Sultana

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Correspondence to Sarwat Sultana.

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Ali, F., Sultana, S. Repeated short-term stress synergizes the ROS signalling through up regulation of NFkB and iNOS expression induced due to combined exposure of trichloroethylene and UVB rays. Mol Cell Biochem 360, 133–145 (2012). https://doi.org/10.1007/s11010-011-1051-7

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  • DOI: https://doi.org/10.1007/s11010-011-1051-7

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