Vitamins C and E protect hepatic cytochrome P450 dysfunction induced by polymicrobial sepsis.
The effect of vitamins C and E on the activity and gene expression of hepatic microsomal cytochrome P450 (CYP) during polymicrobial sepsis was studied. The serum aminotransferase and lipid peroxidation levels increased 24 h after the cecal ligation and puncture, and this increase was attenuated by vitamins C and E. The hepatic concentrations of the reduced glutathione decreased in the septic animals, which was inhibited by vitamin C. Both the activities and mRNA expression of CYP1A1 and CYP2E1 decreased after cecal ligation and puncture, which was prevented by vitamins C and E. The decrease in CYP1A2 activity in the liver from cecal ligation and puncture was prevented by vitamins C and E. Our findings suggest that vitamins C and E improve hepatic drug metabolizing dysfunction as indicated by abnormalities in CYP isoforms during sepsis, and this protection is, in major part, caused by decreased oxidant stress and lipid peroxidation.
Kim
Joo-Young
JY
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, South Korea.
Lee
Sun-Mee
SM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001483:Base Sequence; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D003580:Cytochromes; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000201:enzymology*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D003580:Cytochromes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D019392:Cytochrome P-450 CYP2E1; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000637:Transaminases; D005978:Glutathione; D001205:Ascorbic Acid