N-Nitrosodimethylamine Changes the Expression of Glutathione S-Transferase in the Liver of Male Mice: The Role of Antioxidants

The present study investigated the protective effect of gossypol, selenium, zinc, or glutathione (GSH) against dimethylnitrosamine (DMN)-induced hepatotoxicity in the livers of male mice. The expression and the activity of glutathione S-transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as well as the activity of glutathione reductase were determined after the treatment of mice for seven consecutive days with low or high doses of gossypol, selenium, zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2 h after the repeated dose treatments of mice for seven consecutive days with each antioxidant. DMN reduced the expression and inhibited the activity of GST. However, repeated treatments of mice with low-dose gossypol or high dose of either selenium or GSH followed by a single dose of DMN induced the expression and the activity of GST. In contrast, low-dose treatments of mice with zinc, selenium, or GSH followed by a single dose of DMN reduced the expression and the activity of GST compared to either control or DMN-treated groups. In addition, high-dose treatment with either gossypol or selenium markedly induced the levels of GSH compared to either control or DMN-treated groups. Interestingly, pretreatment of mice with high dose of either gossypol or selenium for seven consecutive days followed by a single dose of DMN decreased the levels of MDA, whereas DMN induced such levels. It is concluded that high dose of either gossypol or selenium is a stronger protector than zinc and GSH in ameliorating the toxic effects of DMN. (C) 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:389-395, 2008; Published online in Wiley InterScience (www.interscience.wiley.corn). DOI 10:1002/jbt.20255