Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
Mol Cell Biochem. 2012 Jan;360(1-2):133-45. doi: 10.1007/s11010-011-1051-7. Epub 2011 Sep 27.
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, H(2)O(2) 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.
应激会促进各种慢性炎症性疾病的发生。本研究旨在评估重复短期应激(RRS)对细胞转导的影响,以及三氯乙烯(TCE)和紫外线(UVB)联合暴露引起的氧化应激和早期肿瘤促进生物标志物的影响。RRS 导致有毒物质暴露后小鼠表皮组织中应激反应性细胞转导元件 NFkB-p65 的表达增加和诱导型一氧化氮合酶(iNOS)的活性增加。RRS 加剧了细胞抗氧化机制的急剧耗竭,这表现在 GSH(谷胱甘肽和 GSH 依赖性酶)、超氧化物歧化酶和过氧化氢酶活性明显减少(P < 0.001),脂质过氧化、H2O2 和黄嘌呤氧化酶活性增加(P < 0.001),应激动物中的 DT-黄递酶活性下调(P < 0.001)。由于 NFkB-p65 和诱导型一氧化氮合酶表达的诱导可能导致过度增殖,我们估计在小鼠皮肤中多胺的合成显著增加(P < 0.001),这可以通过鸟氨酸脱羧酶来证明,鸟氨酸脱羧酶是肿瘤促进的早期标志物,并且进一步评估了 PCNA 表达。所有这些发现都表明重复短期应激在 TCE 和 UVB 辐射的毒性反应中具有协同作用。