Influence of vitamin E on alcohol-induced changes in antioxidant defenses in mice liver.
It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. Redox-sensitive transcription factors nuclear factor-kappaB (NFkappaB) and activator protein-1 (AP1) are involved in development of alcohol-related diseases. Because of its antioxidative properties, vitamin E is believed to prevent diseases associated with oxidative stress. The aim of the present study was to evaluate the molecular mechanism associated with alcohol-induced oxidative stress and its prevention with vitamin E supplementation. Male Balb/c mice were divided into three groups viz. group I (control), group II (alcohol-treated) and group III (alcohol-treated + Vitamin E supplemented). Group II received 8% alcohol as sole source of drinking fluid while group III was given Vitamin E orally as 5 IU/kg body weight along with 8% alcohol. After 15 days, increases in lipid peroxidation, catalase and GST activity and decreases in SOD activity as well as redox ratio were observed in group II. This was associated with increased apoptosis in this group. Vitamin E supplementation restored the redox status, reduced apoptosis and prevented oxidative stress. Further mRNA expression of cjun, cfos, p65 (NFkappaB) showed increased expression during oxidative stress in group II. Although inhibition in NFkappaB activation was observed with Vitamin E, on the contrary it stimulated AP1 expression. This study supports the fact that alcohol promoted oxidative stress and is the major cause of alcohol toxicity in liver. Vitamin E can mitigate the toxic effects of alcohol and can be suitably used as a potential therapeutic agent for alcohol-induced oxidative damage in liver.
Kaur
Jasmeet
J
Department of Biophysics, Panjab University, Chandigarh 160014, India.
Shalini
Sonia
S
Bansal
M P
MP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D020672:I-kappa B Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C498144:Rela protein, mouse; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014810:Vitamin E; D000431:Ethanol; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione