Evaluation of acute and chronic hepatotoxic effects exerted by anabolic-androgenic steroid stanozolol in adult male rats

Stanozolol (ST) is a 17 alpha-alkyl anabolic-androgenic steroid (17 alpha-A AS) often misused by athletes and bodybuilders. The use of anabolic-steroid s by sportsmen and teenagers has increased dramatically, thus raising the q uestion about their hepatotoxicity, specially those such as ST which are or ally administered. Previously, we have reported diverse in vivo effects exe rted by this steroid and published the existence of a highly specific ST-bi nding site in male rat liver microsomes. The existence of this binding site , the reported hepatic effects exerted in humans, and the very limited info rmation about its potential hepatotoxicity led us to treat adult male rats acutely and chronically with ST and study different parameters that could i ndicate liver damage: serum levels of transaminases, concentration of monoo xygenase enzymes in liver, liver membrane lipid peroxidation products, live r histopathology, and cell cycle/ploidy status of liver cells. In our study , no changes in serum transaminases or lipid peroxidation levels were obtai ned. However, acute stanozolol treatment significantly decreased the levels of cytochrome P450 (Cyt. P450) and cytochrome b(5) (Cyt. b(5)) during the first 48 h of treatment, while subsequently, at 72 and 96 h, these microsom al enzymes underwent a significant increase in their levels. In sharp contr ast with this response to acute treatment, the content of these two enzymes during chronic treatment showed an important decrease. Interestingly, acut ely and chronically ST-treated livers showed slight to moderate inflammator y or degenerative lesions in centrilobular hepatocytes. Flow cytometric ana lysis demonstrated that both acute and chronic ST treatment were capable of increasing the percentage of S-phase fraction (%SPF) of liver cells. These findings taken together clearly show that this steroid is capable of alter ing the liver capacity for metabolizing xenobiotics and indicate that high doses of ST could exert a proliferative effect on liver cells. Such data sh ould be considered in risk evaluations for this compound.