An examination of various mechanisms for ethanol-induced testicular injury: studies utilizing the isolated perfused rat testes.

Abstract

The effect of ethanol, acetaldehyde, and acetate upon testicular production of testosterone was studied utilizing the isolated perfused rat testes. In addition, effects of 4-methylpyrazole (an inhibitor of alcohol dehydrogenase) and methylene blue (a proton acceptor) were evaluated alone and with addition of ethanol. Finally, the effect of penicillamine (a drug that forms a Schiff base with acetaldehyde) alone and with the addition of acetaldehyde to the perfusion medium was assessed. No changes in testicular light microscopic appearance and ATP content were noted as a result of the 2 h of perfusion. Testosterone production by the isolated perfused testes was reduced in a dose-related manner by the addition of ethanol over a range of concentrations from 50–150 mg/dl. Moreover, both acetaldehyde and acetate, products of ethanol and acetaldehyde metabolism, respectively, also inhibited testicular production of testosterone. In contrast, the addition of 4-methylpyrazole or methylene blue to the perfusion medium did not alter testosterone production significantly when compared to control perfusions without these additives. Both agents however, completely prevented the adverse effects of ethanol upon testosterone production. Finally, penicillamine was found to prevent completely the reduction of testosterone production associated with the addition of acetaldehyde to the perfusate. From these results we conclude that 1) ethanol is a gonadal toxin; 2) acetaldehyde and acetate can reduce testosterone production by the isolated perfused rat testes; and 3) the toxic effects of these materials can be prevented by the addition of drugs known to inhibit alcohol dehydrogenase activity, prevent redox changes, or form Schiff bases with acetaldehyde.