Effects of ascorbic acid on iproniazid-induced hepatitis in phenobarbital-treated rats

The effects of ascorbic acid (AA) on hepatic injury induced by iproniazid (IPN) in phenobarbital-treated rats were investigated by the evaluation of hepatic function using the clearance of aminopyrine (AM). Either IPN or isopropylhydrazine (IP-Hy), a potent toxic metabolite of IPN, were administered as a pretreatment to rats with or without AA. After i.v. injection of AM, the blood concentration of AM was determined by capillary gas chromatography by isotope dilution analysis using deuterium-labeled AM (AM-d9) as the internal standard. The kinetic parameters of AM, Vd, kel and total body clearance, were estimated from the time course of blood concentration. Pretreatment with IPN with AA led to a marked increase in the kel and in the clearance compared with pretreatment using IPN alone. A significant increase in the kel and the clearance was also found in the case of combined pretreatment using IP-Hy with AA. The effects of AA on the hepatic injury induced by IPN were studied according to its histological aspects. In the specimens obtained following the administration of IPN or IP-Hy with AA, the degree of cell necrosis was remarkably lowed both quantitatively and qualitatively. The present results clearly demonstrate that AA was effective in reducing IPN-induced hepatitis.