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
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.
KeywordsRepeated restraint stress NFkB-p65 iNOS ODC PCNA
Repeated restraint stress
Nuclear factor kappa B
Inducible nitric oxide synthase
Proliferating cell nuclear antigen
Nicotinamide adenine dinucleotide phosphate
Author Sarwat Sultana is thankful to University Grants Commission, Govt. of India, New Delhi, for providing Meritorious Research Fellowship to her student Farrah Ali.
Conflict of interest
Authors state no conflict of interest.
- 13.Aberg KM, Radek KA, Choi EH, Kim DK, Demerjian M, Hupe M, Kerbleski J, Gallo RL, Ganz T, Mauro T, Feingold KR, Elias PM (2007) Psychological stress down regulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice. J Clin Invest 117(11):3339–3349PubMedCrossRefGoogle Scholar
- 19.Barthelman M, Chen W, Gensler HL, Huang C, Dong Z, Bowden GT (1998) Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation. Cancer Res 15;58(4):711–716Google Scholar
- 24.Shen T, Zhu QX, Yang S, Wu CH, Zhang HF, Zhou CF, Zhang XJ (2008) Trichloroethylene induced cutaneous irritation in BALB/c hairless mice: histopathological changes and oxidative damage, Toxicology; 248(2–3:113–120Google Scholar
- 28.Zhu QX, Ma T, Shen T, Yu Y, Ye LP, Ding R, Yu JF (2007) Cytotoxicity of trichloroethylene in keratinocytes involving alterations of mitochondrial function and ultrastructure. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 25(5):263–266Google Scholar
- 29.Kamijima M, Wang H, Huang H, Li L, Shibata E, Lin B, Sakai K, Liu H, Tsuchiyama F, Chen J, Okamura A, Huang X, Hisanaga N, Huang Z, Ito Y, Takeuchi Y, Nakajima T (2008) Trichloroethylene causes generalized hypersensitivity skin disorders complicated by Hepatitis. J Occup Health 50(4):328–338PubMedCrossRefGoogle Scholar
- 32.Shen T, Zhu QX, Yang S, Ding R, Ma T, Ye LP, Wang LJ, Liang ZZ, Zhang XJ (2007) Trichloroethylene induces nitric oxide production and nitric oxide synthase mRNA expression in cultured normal human epidermal keratinocytes. Toxicology 8;239(3):186–194Google Scholar
- 35.Sharma S, Khan N, Sultana S (2005) Balsamodendron mukul suppresses benzoyl peroxide and ultraviolet light induced tumor promotional events in Swiss mice. J Photochem Photobiol B 14;78(1):43–51Google Scholar
- 42.Stripe F, Della-Corte E (1969) The regulation of rat liver xanthine oxidase. Conversion in vitro of enzyme activity from dehydrogenase (type D) to oxidase (type O). J Biol Chem 244:3855–3863Google Scholar
- 45.Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferase. The first enzymatic step in mercapturic acid formation. J. Biol Chem 249(22):7130–7139Google Scholar
- 46.Claiborne (1985) Catalase activity. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC press, Boca Raton, FL, pp 283–284Google Scholar
- 48.Benson A, Hunkeler M, Talalay P (1980) Increase of NADPH; quinone reductase activity by dietary antioxidant, possible role in protection against carcinogenesis and toxicity. Proct Natl Acad Sci USA 5116–5620Google Scholar
- 61.Ernster L (1967) DT-diaphorase. Methods Enzymol (10):309–317Google Scholar