Immunochemical detection of hepatic cocaine-protein adducts in mice

Chemical Research in Toxicology
F M Ndikum-MofforS M Roberts

Abstract

Cocaine is capable of producing hepatic necrosis in laboratory animals and humans. Studies in mice indicate that N-oxidative metabolism of cocaine is required for hepatotoxicity and have suggested that toxicity may result from the adduction of proteins by cocaine-reactive metabolites. To aid in identifying protein targets for cocaine-reactive metabolites, an antibody was raised in rabbits immunized with cocaine linked via the tropane nitrogen to a carrier protein (bovine serum albumin). Hepatic proteins from cocaine-treated mice (ICR males, 50 mg of cocaine/kg of body weight, ip) and saline-treated controls were prepared from whole liver homogenate or following subcellular fractionation, and Western blot analyses of hepatic proteins using this antibody were conducted following one- and two-dimensional SDS-PAGE. Analysis of liver homogenate from cocaine-treated mice revealed major protein targets with approximate molecular masses of 20 kDa (pI = 6.0), 44 kDa (two proteins with pI's of 5.0 and 7.0), 52-54 kDa (pI = 4.5), and 64 kDa (pI = 5.5). These specific protein targets were shown to be localized in the mitochondria and microsomes. Several minor bands of immunoreactivity were also seen in mice treated with cocaine, but not in...Continue Reading

References

May 1, 1991·Journal of Hepatology·M O SilvaE R Schiff
Jan 1, 1980·Methods in Enzymology·B A Hurn, S M Chantler

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Citations

Jan 11, 2003·Journal of Toxicology and Environmental Health. Part a·Ramez LabibRita Turkall
Apr 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K Selim, N Kaplowitz
Nov 13, 2013·Drug Discovery Today·Saifur R KhanArno G Siraki
Apr 21, 2001·Toxicology and Applied Pharmacology·M J Reid, L M Bornheim
Oct 12, 2013·Chemical Research in Toxicology·Kevin J Schneider, Anthony P DeCaprio
Jul 13, 2000·Electrophoresis·S Steiner, F A Witzmann
Aug 3, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R Allen GillilandAnthony P DeCaprio
Jun 24, 2003·Biochemical Pharmacology·Florence M Ndikum-Moffor, Stephen M Roberts

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