Cocaine hepatotoxicity in mice: histologic and enzymatic studies.
The severity of hepatotoxicity in CF-1 mice given 5 daily doses of 5, 10, and 20 mg cocaine/kg body weight and sacrificed 24 hr after the last injection appeared to be dose-dependent. Using light microscopy, the hallmark of cocaine early toxicity was manifested by pallor and ballooning of the hepatocytes in the midzonal and then in the centrilobular areas. Degeneration and necrosis of the liver cells in the same zones were encountered while the hepatocytes in the periportal areas remained intact. When examined under the electron microscope, such pallor and ballooning of the hepatocytes appeared to to be due to dilation of the rough endoplasmic reticulum (RER) profiles which often revealed a significant loss of their ribosomes. Dilation of the smooth endoplasmic reticulum (SER) was also common and moderate proliferation of peroxisomes was frequently seen. In the degenerating hepatocytes, the 2 forms of endoplasmic reticulum were difficult to recognize and the peroxisomes appeared sparse. Cocaine treatment elevated the level of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in a dose-dependent manner. Although hepatic cytochrome P450 was slightly increased in the low dose groups, a reduction in the enzyme activity was noticed in the group treated with 20 mg cocaine/kg. However, hepatic reduced glutathione content manifested a significant increase in the group which received 20 mg cocaine/kg.
Mehanny
S Z
SZ
Department of Pharmacology/Toxicology, New Jersey Medical School UMDNJ, Newark 07103-2714.
Abdel-Rahman
M S
MS
D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D003042:Cocaine / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005978:Glutathione / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice
D003577:Cytochrome P-450 Enzyme System; D001219:Aspartate Aminotransferases; D005978:Glutathione; D003042:Cocaine