Advertisement

Archives of Toxicology

, Volume 73, Issue 8–9, pp 465–472 | Cite as

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

  • Luis D. Boada
  • Manuel Zumbado
  • Santiago Torres
  • Antonio López
  • Bonifacio N. Díaz-Chico
  • Juan J. Cabrera
  • Octavio P. Luzardo
ORGAN TOXICITY AND MECHANISMS

Abstract

Stanozolol (ST) is a 17α-alkyl anabolic-androgenic steroid (17α-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.

Key words Stanozolol Hepatotoxicity Monooxygenase enzymes Cell cycle S-phase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Luis D. Boada
    • 1
  • Manuel Zumbado
    • 1
  • Santiago Torres
    • 2
  • Antonio López
    • 2
  • Bonifacio N. Díaz-Chico
    • 2
  • Juan J. Cabrera
    • 3
  • Octavio P. Luzardo
    • 1
  1. 1.Department of Clinical Sciences, Laboratory of Toxicology, Health Sciences Center and Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, P.O. Box 550, 35080 Las Palmas de Gran Canaria, Spain Tel.: 34 928453472; Fax: 34 928451416ES
  2. 2.Department of Biochemistry, Molecular Biology, Physiology, Immunology and Genetics (Lab. of Physiology), Health Sciences Center and Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, P.O. Box 550, E-35080 Las Palmas de Gran Canaria, SpainES
  3. 3.Department of Morphology, Health Sciences Center and Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, P.O. Box 550, 35080 Las Palmas de Gran Canaria, SpainES

Personalised recommendations