DECREASED GLUTATHIONE-PEROXIDASE ACTIVITY IN MICE IN RESPONSE TO NAFENOPIN IS CAUSED BY CHANGES IN SELENIUM METABOLISM

The activity of selenium-dependent glutathione peroxidase is known to be reduced in the liver of both rats and mice after exposure to nafeno pin, as well as other peroxisome proliferators. The mechanism for this down-regulation is not known, but might involve changes in incorporat ion of selenium into selenoproteins. In this paper we show that both i ncorporation of selenium into selenoproteins and the level of selenium in liver is reduced in mice treated with nafenopin. The activity of s elenium dependent glutathione peroxidase (GPx), as well as incorporati on of selenium into its 23 kD subunit were found to be decreased. Cont rary to what might have been expected, the decreased GPx activity was detected concomitantly with a slight increase in mRNA levels after 10 days of treatment, while a small decrease in mRNA levels was detected in treated animals after 26 weeks, together with the decrease in GPx-a ctivity. Incorporation of selenium into liver fatty acid binding prote in (L-FABP) was also decreased, even though large increases in protein and mRNA levels were detected. Taken together these data suggest that the decrease in GPx-activity in response to nafenopin is due to post- transcriptional mechanisms, involving changes in selenium metabolism.