The roles of Kupffer cells in hepatocellular dysfunction after femur fracture trauma in rats.
The aim of this study was to investigate the effects of trauma on alterations in cytochrome P450 (CYP 450)-dependent drug metabolizing function and to determine the role of Kupffer cells in hepatocellular dysfunction. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia, while control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl3) was injected intravenously via the tail vein at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h after FFx, serum alanine aminotransferase (ALT) activity was increased, and this increase was attenuated by GdCl3 pretreatment. Serum aspartate aminotransferase (AST) and lipid peroxidation levels were not changed by FFx. Hepatic microsomal CYP 450 content and aniline p-hydroxylase (CYP 2E1) activity were significantly decreased; decreases that were not prevented by GdCl3. The level of CYP 2B1 activity was decreased by Kupffer cell inactivation, but not by FFx. There were no significant differences in the activities of CYP 1A1, CYP 1A2 and NADPH-CYP 450 reductase among any of the experimental groups. Our findings suggest that FFx trauma causes mild alterations of hepatic CYP 450-dependent drug metabolism, and that Kupffer cells are not essential for the initiation of such injury.
Lee
Woo-Yong
WY
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu Suwon, Gyeonggi-do 440-746, Korea.
Lee
Sun-Mee
SM
D000818:Animals; D002374:Catalase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D005264:Femoral Fractures / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase