The influence of 4-methylpyrazole on the acute hepatotoxic actions of seven aliphatic alcohols

Using isolated, hemoglobin-free, perfused rat livers we studied the effect of inhibition of alcohol dehydrogenase (ADH) by 4-methylpyrazole (4-MP) on the acute hepatotoxic effects of ethanol, 1-propanol, 1-butanol, 1-pentanol, 2-methyl-1-propanol, 2-methyl-1-butanol and 3-methyl-1-butanol. These alcohols were administered to the liver perfusate at an initial concentration of 130.2 mmol/L which corresponded to a 6% (w/v) concentration of ethanol. The alcohol induced hepatic damage revealed itself as an increased leakage of enzymes (GPT, LDH, GLDH) into the perfusate, and decreases in oxygen consumption, bile secretion, perfusion flow, and hepatic concentrations of ATP and GSH. With the exception of the fall in bile secretion, 4-MP inhibited the toxic actions of ethanol completely and those induced by 1-propanol partially. The hepatic injury induced by the other alcohols, however, was not inhibited by 4-MP at all. It is concluded that with increasing carbon chain length, the ability of the unchanged molecule to produce hepatotoxicity increases while that of the ADH metabolized decreases.