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.