Evaluation of the differential in vivo toxic effects of ethanol and acetaldehyde on the hypothalamic-pituitary-gonadal axis using 4-methylpyrazole.
4-Methylpyrazole (4-MP) blocks ethanol (ETOH) oxidation by inhibiting alcohol dehydrogenase (ADH). Because ADH has been identified and shown to be active in the testes, we examined the effect of ETOH + 4-MP in the ETOH-fed rat model. Weanling rats were divided into four groups of 15 rats each and fed a liquid diet: group I received ETOH (5% v/v) + 4-MP (1.34 mM); group II was pair-fed the diet containing only 4-MP and isocalorically matched to group I; group III received ETOH diet; and group IV was pair-fed isocalorically to match group III. Using two-way analysis of variance for nonorthogonal data, the results were analyzed to examine both ETOH and 4-MP as the main treatment and to test for interaction. Both ETOH and 4-MP produced significant main treatment effects with significant interaction on liver/body ratio, testes weight expressed as per cent of normal, and plasma luteinizing hormone levels, and without interaction on plasma testosterone concentrations.