EFFECTS OF ASCORBIC-ACID ON IPRONIAZID-INDUCED HEPATITIS IN PHENOBARBITAL-TREATED RATS

The effects of ascorbic acid (AA) on hepatic injury induced by ipronia zid (IPN) in phenobarbital-treated rats were investigated by the evalu ation of hepatic function using the clearance of aminopyrine (AM). Eit her IPN or isopropylhydrazine (IP-Hy), a potent toxic metabolite of IP N, were administered as a pretreatment to rats with or without AA. Aft er i.v. injection of AM, the blood concentration of AM was determined by capillary gas chromatography by isotope dilution analysis using deu terium-labeled AM (AM-d(9)) as the internal standard. The kinetic para meters of AM, V-d, k(el) 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 k(el) and in the clearance compared w ith pretreatment using IPN alone. A significant increase in the k(el) 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 b y IPN were studied according to its histological aspects. In the speci mens obtained following the administration of IPN or IP-Hy with AA, th e degree of cell necrosis was remarkably lowed both quantitatively and qualitatively. The present results clearly demonstrate that AA was ef fective in reducing IPN-induced hepatitis.