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The Roles of Kupffer Cells in Hepatic Dysfunction Induced by Ischemia/Reperfusion in Rats  

Jung Joo-Yeon (Narcotic and Neuropharmacological Drug Division, Drug Evaluation Department, Korea Food and Drug Administration)
Lee Sun-Mee (College of Pharmacy, Sungkyunkwan University)
Publication Information
Archives of Pharmacal Research / v.28, no.12, 2005 , pp. 1386-1391 More about this Journal
Abstract
This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (ls/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride ($GdCl_{3}$, 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. $GdCl_{3}$ significantly attenuated these increases. Is/Rp markedly decreased the bile. flow and cholate output, and $GdCl_{3}$ restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by $GdCl_{3}$. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. $GdCl_{3}$ 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.
Keywords
Ischemia/reperfusion; Hepatic secretion; Drug metabolism; Gadolinium chloride; Kupffer cells;
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