Preventive effect of neutropenia on carbon tetrachloride-induced hepatotoxicity in rats.
The preventive effect of neutropenia on carbon tetrachloride (CCl4)-induced hepatotoxicity was examined in rats. In rats treated once with CCl4 (1 ml kg(-1), i.p.), the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indices of liver cell damage, and the hepatic activity of myeloperoxidase (MPO), an index of tissue neutrophil infiltration, increased at 6 h after the intoxication and further increased at 24 h. The liver of CCl4 -treated rats showed an increase in the concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and decreases in superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration at 6 h after the intoxication followed by a further increase in TBARS concentration and further decreases in SOD activity and GSH concentration at 24 h with increased xanthine oxidase (XO) activity at 24 h. Neutropenic treatment with anti-rat neutrophil antiserum (2 ml kg(-1), i.p.) at 0.5 h after CCl4 intoxication attenuated the increases in serum ALT and AST activities and hepatic MPO activity and TBARS concentration and the decreases in hepatic SOD activity and GSH concentration found at 6 and 24 h after CCl4 intoxication and the increase in hepatic XO activity found at 24 h after the intoxication. This neutropenia reduced the necrotic and degenerative changes with inflammatory cell infiltration in the liver cell of CCl4 -treated rats. These results indicate that neutropenia prevents CCl4 -induced hepatotoxicity in rats by attenuating the disruption of hepatic reactive oxygen species metabolism mediated by neutrophils accumulating in the liver tissue.
Ohta
Yoshiji
Y
Department of Chemistry, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan. yohta@fujita-hu.ac.jp
Imai
Yoichiro
Y
Matsura
Tatsuya
T
Kitagawa
Akira
A
Yamada
Kazuo
K
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D007167:Immunotherapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009503:Neutropenia / Q000503:physiopathology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014969:Xanthine Oxidase / Q000378:metabolism
D000906:Antibodies; D017392:Thiobarbituric Acid Reactive Substances; D009195:Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D000637:Transaminases; D005978:Glutathione