Journal of Drug Metabolism & Toxicology
Open Access

Abstract

Testosterone and Estradiol Affect Renal Oxidative Metabolism and Glutathione Pathway of Wistar Rats

Stefano Maso, Annamaria Nicolli, Alberto Gambalunga, Michele Mongillo, Federica Chiara, Andrea Trevisan

The impact of sexual hormones on kidney metabolism may be relevant to modulate the effect of nephrotoxic substances. In the present research the effects of castration, testosterone, and estradiol on renal oxidative metabolism [cytochrome P-450 (CYP)], glutathione pathway [glutathione content (GSH), glutathione S-transferases (GST) activities, and cysteine-conjugate ß-lyase [as glutamine transaminase K (GTK) activity] have been studied. Naive male rats have a significantly lower GSH content but show a significantly higher GST activities and CYP content than females, whereas no sex difference was for GTK activity. Castration significantly reduces GSH content and GTK activity in females and CYP content in males, partially but significantly restored by testosterone. Testosterone significantly increases GSH content and GTK activity in males and GTK activity and CYP content in females. Estradiol increases GSH content in males, whereas decreases GST activities in females and CYP content in both sexes. Castration followed by testosterone treatment increases GTK activity in both sexes whereas increases CYP content and reduces GSH content in females. Castration followed by estradiol treatment increases GSH content and reduces GST activities in males and CYP content in both sexes. In conclusion, the results suggest that sex hormones influence metabolic pathways of the kidney and that they are probably responsible of the sex- related differences of chemical-induced nephrotoxicity. An univocal model to define sex-related toxicity of xenobiotic substances is far to be identified.