The roles of Kupffer cells in hepatic dysfunction induced by ischemia/reperfusion in rats.
This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (Is/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride (GdCl3, 7.5 mg/kg body weight, intravenously) was used to inactivate the Kupffer cells 1 day prior to ischemia. Is/Rp markedly increased the serum aminotransferase level and the extent of lipid peroxidation. GdCl3 significantly attenuated these increases. Is/Rp markedly decreased the bile flow and cholate output, and GdCl3 restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by GdCl3. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. GdCl3 prevented the increase in the aniline p-hydroxylase activity. Overall, Is/Rp diminishes the hepatic secretory and microsomal drug-metabolizing functions, and Kupffer cells are involved in this hepatobiliary dysfunction.
Jung
Joo-Yeon
JY
Narcotic and Neuropharmacological Drug Division, Drug Evaluation Department, Korea Food and Drug Administration, Seoul, Korea.
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D020355:Cholates / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004195:Disease Models, Animal; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000293:injuries / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*
D020355:Cholates; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D005682:Gadolinium; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D000410:Alanine Transaminase; C038958:gadolinium chloride