Role of metabolism in 1-bromopropane-induced hepatotoxicity in mice.

Sang Kyu Lee, Mi Jeong Kang, Tae Won Jeon, Hyun Woo Ha, Jin Woo Yoo, Gyu Sub Ko, Wonku Kang, Hye Gwang Jeong, Won Seok Lyoo, Tae Cheon Jeong

Index: J. Toxicol. Environ. Health A 73(21-22) , 1431-40, (2010)

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Abstract

A possible role of metabolism in 1-bromopropane (1-BP)-induced hepatotoxicity was investigated in male ICR mice. The depletion of glutathione (GSH) by formation of GSH conjugates was associated with increased hepatotoxicity in 1-BP-treated mice. The formation of S-propyl and 2-hydroxypropyl GSH conjugates were identified in the liver following 1-BP treatment. In addition, the formation of reactive metabolites of 1-BP by certain cytochrome P-450 (CYP) may be involved in 1-BP-induced hepatotoxicity. The decreased content of hepatic GSH produced by 1-BP was associated not only with increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but also with elevated levels of hepatic thiobarbituric acid-reactive substance (TBARS) in mice where metabolic enzymes were induced by pretreatment with phenobarbital. In addition, the hepatotoxicity induced by 1-BP was prevented by pretreatment with SKF-525A. Taken together, the formation of reactive metabolites by CYP and depletion of GSH may play important roles in hepatotoxicity induced by 1-BP.