Cocaine hepatotoxicity during protein undernutrition of retrovirally infected mice.
Effects of cocaine administration on lipid peroxidation and liver damage in immunocompromised mice fed different levels of dietary proteins were investigated. Indices of lipid peroxidation and serum aminotransferases as evidence of free radical attack and liver damage were compared in mice fed a low protein (4%) or regular protein diet (20% protein) for 3 weeks and then infected with murine leukemia virus and given daily intraperitoneal injections of increasing progressive doses of 5-45 mg.kg-1.day-1 of cocaine for 11 weeks. Cocaine administration significantly increased hepatic triglycerides, serum aminotransaminases, conjugated dienes, lipid fluorescence, and malondialdehyde levels. These changes were exacerbated by retroviral infection and also by protein undernutrition. Retroviral infection additively increased indices of cocaine-induced lipid peroxidation and hepatic damage. Significant increases in indices of lipid peroxidation and greater liver injury were also detected in similarly treated mice that received the low protein diet compared with well-nourished mice. These results show that immunocompromised mice fed low levels of dietary protein form significantly increased immunogenic lipid peroxidation adducts during cocaine treatment.
Odeleye
O E
OE
Department of Family Medicine, University of Arizona, Tucson 85724.
Lopez
M C
MC
Smith
B T
BT
Eskelson
C D
CD
Watson
R R
RR
D000818:Animals; D001835:Body Weight; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D009052:Leukemia Virus, Murine; D007942:Leukemia, Experimental / Q000150:complications / Q000503:physiopathology; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011502:Protein-Energy Malnutrition / Q000150:complications*; D012192:Retroviridae Infections / Q000150:complications*; D013231:Steatitis / Q000139:chemically induced / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D000637:Transaminases; D003042:Cocaine