Altered activity of cytochrome P450 in alcoholic fatty liver exposed to ischemia/reperfusion.
Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality in liver surgery and transplantation, and fatty livers are susceptible to greater I/R injury and a higher incidence of primary graft nonfunction after transplantation. Because alcohol intake and obesity are major causes of fatty liver, this study was initiated to investigate the effect of chronic ethanol consumption on hepatic microsomal cytochrome P450 (CYP) activity after I/R. Rats were fed an alcohol liquid diet or a control isocaloric diet for 4 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. It was found that, chronic ethanol consumption significantly increased liver weight, serum triglyceride (TG), liver TG, and serum aminotransferase activities. Moreover, alcoholic fatty livers exposed to I/R showed significantly higher levels of aminotransferase activities than the controls. No significant differences in microsomal CYP content or CYP1A1 activity were found between I/R treated animals fed a control diet (the CD + I/R group) and I/R treated animals fed an ethanol containing diet (the ED + I/R group). Moreover, whereas CYP1A2 activity was decreased in the ED + I/R group versus the CD + I/R group, CYP2E1 activity was elevated. Additionally, chronic alcohol consumption up-regulated TNF-alpha and IL-6 mRNA levels immediately after I/R. In conclusion, chronic ethanol consumption was found to potentiate hepatocellular damage as indicated by abnormalities in microsomal drug metabolizing function during I/R.
Cho
Kang-Hun
KH
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002492:Central Nervous System Depressants; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D000431:Ethanol; D005235:Fatty Liver, Alcoholic / Q000150:complications* / Q000201:enzymology; D015850:Interleukin-6 / Q000096:biosynthesis; D007511:Ischemia / Q000150:complications; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D002492:Central Nervous System Depressants; D015850:Interleukin-6; D007527:Isoenzymes; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase