Effects of synthetic androgens on liver function using the rabbit as a model

Area of Science:

• Pharmacology and Toxicology
• Hepatotoxicity Assessment
• Animal Models in Drug Development

Background:

• Evaluating the safety of novel synthetic androgens is crucial.
• Hepatotoxicity is a potential concern with androgenic compounds.
• A reliable animal model is needed for early toxicity screening.

Purpose of the Study:

• To determine if rabbits are a suitable model for assessing synthetic androgen liver toxicity.
• To evaluate the hepatotoxic potential of several novel synthetic androgens.
• To establish a short-term dosing interval for toxicity testing in rabbits.

Main Methods:

• Adult male rabbits were orally dosed with synthetic androgens (MENT, DMAU, 11β-MNTDC) or controls (MT, T).
• Liver toxicity was assessed using serum liver enzymes (ALT, AST, GGT, SDH) and bromsulfonphthalein (BSP) clearance.
• Dosing occurred daily for 13 days, with assessments on days 0, 7, and 14.

Main Results:

• 17α-methyltestosterone (MT) and dimethandrolone-undecanoate (DMAU) showed the highest hepatotoxicity.
• 7α-methyl-19-nortestosterone (MENT) exhibited moderate liver toxicity, while 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC) showed minimal effects.
• All toxic effects resolved within two weeks of dosing cessation, and a no-observed-effect level of 1 mg/kg/d was established for MT, DMAU, and MENT.

Conclusions:

• The rabbit model effectively detected liver toxicity induced by synthetic androgens.
• Bromsulfonphthalein (BSP) clearance and serum liver enzymes are reliable early indicators of androgen hepatotoxicity in rabbits.
• Rabbits represent a promising model for preclinical evaluation of synthetic androgen liver safety.