The effects of alpha-phenyl-tert-butyl nitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice

In the present study we demonstrated the protective effects of the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PEN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PEN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PEN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PEN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TEARS) in livers of PEN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PEN administered rats. The protective effect of PEN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PEN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PEN potentially has therapeutic value for the treatment of hepatitis.