Hepatic injury and lipid peroxidation during ischemia and reperfusion.
We determined the relationship between lipid peroxidation and alterations in hepatic secretory and microsomal function during various periods of hepatic ischemia/reperfusion. Rats were pretreated with alpha-tocopherol or vehicle and then subjected to 30, 60, and 90 min, no-flow hepatic ischemia in vivo with 1 or 5 h of reperfusion. Serum aminotransferase (ALT) level, wet-dry weight ratio, and lipid peroxidation were increased at 1 and 5 h of reperfusion, and these changes were significantly attenuated by alpha-tocopherol. Na+, K+-ATPase activity, and glucose-6-phosphatase activity were significantly decreased in 90-min ischemic rats, and these decreases were ameliorated by alpha-tocopherol. After 90 min of ischemia, bile flow, cholate output, and bilirubin output were markedly decreased by ischemia/reperfusion, and alpha-tocopherol restored the secretion. Cytochrome P450 content was decreased by ischemia/reperfusion and restored by alpha-tocopherol to the level of that found in the sham-operated group. Aminopyrine N-demethylase activity was decreased, and aniline p-hydroxylase was increased in 60-min ischemic rats. The changes in the activities of the two enzymes were prevented by alpha-tocopherol. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions and microsomal drug metabolizing systems in proportion to the duration of ischemia and reperfusion in vivo, and this is associated with increased lipid peroxidation.
Lee
S M
SM
College of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Park
M J
MJ
Cho
T S
TS
Clemens
M G
MG
D000410:Alanine Transaminase / Q000097:blood; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D019826:Cholic Acid / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D000410:Alanine Transaminase; D005952:Glucose-6-Phosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D019826:Cholic Acid; D001663:Bilirubin