Chromium (VI)-induced oxidative stress and apoptosis is reduced by garlic and its derivative S-allylcysteine through the activation of Nrf2 in the hepatocytes of Wistar rats.
Chromium (VI) compounds are genotoxic and carcinogenic in a variety of experimental systems. Garlic and its derivatives possess antioxidant properties to scavenge the toxic radicals. The mechanism by which garlic induces the antioxidant and phase II enzymes during oxidative stress-induced apoptosis is not known. This study aims to evaluate the protective role of aqueous garlic extract (AGE; 200 mg kg(-1) b.w.) and S-allylcysteine (SAC; 100 mg kg(-1) b.w.) on potassium dichromate-induced apoptosis and oxidative stress in the hepatocytes of Wistar rats. Activities of liver marker enzymes such as aspartate transaminase, alanine transaminase and lactate dehydrogenase were found to be increased in the serum of chromium-induced group, whereas administration of garlic extract and SAC restored the enzymes to near normal status. The activities of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase), non-enzymic antioxidants (vitamin C and vitamin E) and the levels of reduced glutathione were found to be decreased, while an increase in lipid peroxidation (LPO) and reactive oxygen species were observed in the liver tissues of chromium-induced group. Administration of AGE and SAC reversed the status of these parameters substantially. Histological and transmission electron microscopic studies support our findings. Confocal microscopic analysis using annexin-V showed the involvement of apoptosis. Further, the expression of a novel transcription factor, nuclear factor-E2 related factor 2 (Nrf2) was investigated using Immunofluorescence and Western blotting. The results show the promising role of Nrf2-mediated antioxidant defense of AGE and SAC against chromium toxicity.
Department of Biochemistry, University of Madras, Guindy campus, Chennai-600 025, India.
Srinivasan
S
Kalayarasan
Narayanan
N
Sriram
Ananthasadagopan
A
Sureshkumar
Ganapasam
G
Sudhandiran
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002274:Carcinogens, Environmental / Q000633:toxicity; D002424:Caustics / Q000633:toxicity; D002857:Chromium / Q000633:toxicity*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005737:Garlic / Q000737:chemistry*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D011192:Potassium Dichromate / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D002274:Carcinogens, Environmental; D002424:Caustics; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D002857:Chromium; C074702:chromium hexavalent ion; C065299:S-allylcysteine; D003545:Cysteine; D011192:Potassium Dichromate