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

Abstract

Stanozolol (ST) is a 17alpha-alkyl anabolic-androgenic steroid (17alpha-AAS) often misused by athletes and bodybuilders. The use of anabolic-steroids by sportsmen and teenagers has increased dramatically, thus raising the question about their hepatotoxicity, specially those such as ST which are orally administered. Previously, we have reported diverse in vivo effects exerted by this steroid and published the existence of a highly specific ST-binding site in male rat liver microsomes. The existence of this binding site, the reported hepatic effects exerted in humans, and the very limited information about its potential hepatotoxicity led us to treat adult male rats acutely and chronically with ST and study different parameters that could indicate liver damage: serum levels of transaminases, concentration of monooxygenase enzymes in liver, liver membrane lipid peroxidation products, liver histopathology, and cell cycle/ploidy status of liver cells. In our study, no changes in serum transaminases or lipid peroxidation levels were obtained. However, acute stanozolol treatment significantly decreased the levels of cytochrome P450 (Cyt. P450) and cytochrome b5 (Cyt. b5) during the first 48 h of treatment, while subsequently, at 72 and 96 h, these microsomal enzymes underwent a significant increase in their levels. In sharp contrast with this response to acute treatment, the content of these two enzymes during chronic treatment showed an important decrease. Interestingly, acutely and chronically ST-treated livers showed slight to moderate inflammatory or degenerative lesions in centrilobular hepatocytes. Flow cytometric analysis 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 altering the liver capacity for metabolizing xenobiotics and indicate that high doses of ST could exert a proliferative effect on liver cells. Such data should be considered in risk evaluations for this compound.

Effects of administering testosterone undecanoate in rats subjected to physical exercise: effects on the estrous cycle, motor behavior and morphology of the liver and kidney

“…Accordingly, chronic use of AAS leads to structural and functional changes in the liver such as cholestatic jaundice, peliotic hepatic hyperplasia and hepatocellular adenomas (Fortunato et al, 2006). Moreover, Boada et al (1999) observed that rats treated with high doses of Stanozolol showed inflammation or degeneration of the central lobe of the liver, a change which is proliferant in all hepatocytes. Burghardt et al (2004) studied the effects of chronic treadmill training on behavioral parameters in rats and concluded that the exploratory locomotor activity, assessed using the open field method, was reduced after training.…”

Endocrinological and Pathological Effects of Anabolic-androgenic Steroid in Male Rats

“…However, biochemical examination has yet to reveal liver dysfunction under these circumstances. Boada et al reported that high doses of stanozolol treatment in male rats resulted in inflammation or degeneration in central lobular hepatocytes and exert a proliferative effect on liver cells [43]. Furthermore, there are some reports indicating that levels of cytocrome P-450 in the liver are decreased in male rats following AAS administration [44].…”

Steroid hormone progesterone induces cell proliferation and abnormal mitotic processes in rat liver

“…Flow cytometry analysis by fine-needle aspiration was carried out immediately. Fine-needle aspiration (25-gauge) was used to obtain liver nuclei from liver specimens, which were processed as described previously (Vindelov and Christensen 1990;Doolittle et al 1992;Boada et al 1999;Torres et al 1999). Cell nuclei were analysed on an EPICS XL-MCL cytometer (Coulter Corporation, Hialeah, Fla., USA).…”

“…The liver effects were analysed in a time-course model (1 day, 5 days and 10 days) in order to evaluate the possible accumulative toxicity. The route of administration was chosen to ensure that as high a quantity of PR as possible was absorbed and distributed throughout the animal tissues and to enhance the sensitivity of the assay (Ha¨llstro¨m et al 1996;Boada et al 1999). The dose of this progestagen selected was the minimal one capable of inducing a clear reproductive effect in our animal model (significant decrease in testis weight and/or cryptorchidism).…”