Abstract
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 s-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.
Highlights
Effects of androgens on drug metabolism of the liver are well known and these are attributed to anabolic properties of the hormones [1,2]
Sexual differences were observed in phase II metabolism : liver glutathione S-transferases (GST) showed that substrate is determinant for the enzyme activity
Castration did not influence growth rate of males (Figure 1B), whereas testosterone treatment caused a significant decrease of the growth in naive and castrated males (Figure 1C-D, p=0.0079 and p=0.0159, respectively); estradiol caused a reduction of the weight under the starting values (Figure 1E-F) in naive and castrated males (p=0.0079 for both)
Summary
Effects of androgens on drug metabolism of the liver are well known and these are attributed to anabolic properties of the hormones [1,2]. Studies of Smith et al [3] showed that androgens regulate cytochrome P450 (CYP) expression in renal mouse: infact CYP content of male mice was 3-4 folds higher than female one. Changes of androgen concentration modified enzyme content, confirming that expression of renal CYP gene is inducible or repressible by male hormones [4,5]. Sexual differences were observed in phase II metabolism : liver glutathione S-transferases (GST) showed that substrate is determinant for the enzyme activity. Renal GST activities were higher with several substrates in female than in male rats [10] and sex differences were found in isophorms of rat and human enzyme [11]. The half-life of renal reduced glutathione (GSH) is shorter in male (29 minutes) than in female (57 minutes) mouse [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
