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Farnesol attenuates 1,2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistar rats
Authors:Khan Rehan  Sultana Sarwat
Affiliation:Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110 062, India
Abstract:Colon cancer is the major health hazard related with high mortality and it is a pathological consequence of persistent oxidative stress and inflammation. Farnesol, an isoprenoid alcohol, has been shown to possess antioxidant, anti-inflammatory and chemopreventive properties. The present study was performed to evaluate the protective efficacy of farnesol against 1,2-dimethylhydrazine (DMH) induced oxidative stress, inflammatory response and apoptotic tissue damage. Farnesol was administered once daily for seven consecutive days at the doses of 50 and 100 mg/kg body weight in corn oil. On day 7, a single injection of DMH was given subcutaneously in the groin at the dose of 40 mg/kg body weight. Protective effects of farnesol were assessed by using caspase-3 activity, tissue lipid peroxidation (LPO) and antioxidant status as end point markers. Further strengthening was evident on histopathological observations used to assess the protective efficacy of farnesol. Prophylactic treatment with farnesol significantly ameliorates DMH induced oxidative damage by diminishing the tissue LPO accompanied by increase in enzymatic viz., superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) and non-enzymatic viz., reduced glutathione (GSH) antioxidant status. Farnesol supplementation significantly decreased caspase-3 activity in colonic tissue. Histological findings also revealed that pretreatment with farnesol significantly reduced the severity of submucosal edema, regional destruction of the mucosal layer and intense infiltration of the inflammatory cells in mucosal and submucosal layers of the colon. The data of the present study suggest that farnesol effectively suppress DMH induced colonic mucosal damage by ameliorating oxidative stress, inflammatory and apoptotic responses.
Keywords:Abbreviations: BSA, bovine serum albumin   CDNB, 1-chloro-2,4-dinitrobenzene   DMH, 1,2-dimethylhydrazine   DTNB, 5,5&rsquo  -dithiobis-(2-nitrobenzoic acid)   EDTA, ethylene diamine tetra acetic acid   GPx, glutathione peroxidase   GR, glutathione reductase   GSH, reduced glutathione   GSSG, oxidized glutathione   GST, glutathione-S-transferase   NADPH, reduced nicotinamide adenine dinucleotide phosphate   QR, quinone reductase   ROS, reactive oxygen species   SOD, superoxide dismutase   TBA, thiobarbituric acid
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