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Cocaine Hepatotoxicity and Its Potentiation by Lipopolysaccharide: Treatment and Gender Effects

¹ Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA
² Department of Clinical Laboratory Sciences, School of Health Related Professions, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA

Correspondence: Address correspondence to M. S. Abdel-Rahman, Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Room I-655, Newark, NJ 07103-2714, USA. E-mail:abdelrms{at}umdnj.edu

This study was conducted to investigate the effect of a 7-day treatment as well as the influence of gender on cocaine hepatotoxicity (CH). Lipopolysaccharide (LPS) potentiation of CH was also investigated. Male and female CF-1 mice were orally administered 20 mg/kg body weight cocaine hydrochloride once daily for 7 days. Four hours after the last cocaine administration, the mice were administered 12 x 10⁶ EU LPS (or equal volume of sterile saline) intraperitoneally. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were evaluated as indices of liver injury. Blood and liver glutathione (GSH), glutathione reductase (GRx), and catalase (CAT) activities were also determined to investigate the oxidation stress induced by the treatment. Plasma ALT and AST concentrations were elevated in all males receiving cocaine alone or cocaine + LPS. Furthermore, blood GSH and CAT were decreased and GRx activity was elevated in the same males. Histological analysis revealed a high degree of focal necrosis in the male cocaine group, and severe necrosis in the male cocaine + LPS group. Unlike males, females showed no effect of either cocaine alone or cocaine + LPS treatments. These results indicate that gender plays a significant role in CH and its potentiation by LPS and lengthening the administration by two treatments increased the severity of cocaine + LPS hepatotoxicity dramatically in male mice.

Key Words: Cocaine • Gender • Hepatotoxicity • LPS • Mouse • ROS

International Journal of Toxicology, Vol. 23, No. 3, 163-170 (2004)
DOI: 10.1080/10915810490471334


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				T. Visalli, R. Turkall, and M. S Abdel-Rahman Influence of Gender on Cocaine Hepatotoxicity in CF-1 Mice International Journal of Toxicology, January 1, 2005; 24(1): 43 - 50. [Abstract] [Full Text] [PDF]