Polyamine Protection Against Chemically Induced Hepatotoxicity

Abstract

The protective effect of putrescine (a polyamine) on chemically induced hepatotoxicity in male Sprague-Dawley rats was assessed by mortality, clinical pathological changes (specifically alanine aminotransferase and aspartate aminotransferase activities), and liver histopathological changes. A reduction in hepatotoxicant-induced mortality by 20% to 25% was observed when putrescine (100 mg/kg/day) was administered intraperitoneally for 3 days prior to hepatotoxicant administration (either carbon tetrachloride or allyl alcohol at dose levels approximating the LD₅₀). Putrescine significantly reduced the hepatoxicant-induced increases in serum alanine aminotransferase and aspartate aminotransferase activities. Histological assessment revealed that putrescine pretreatment also reduced the severity and frequency of hepatotoxicant-induced liver necrosis. Administration of putrescine at 0.5 and 3 hours following hepatotoxicant treatment decreased both hepatoxicant-induced mortality and hepatoxicant-induced increases in serum alanine aminotransferase and aspartate aminotransferase activities, with the 0.5 hour postdose treatment being more effective than the 3 hours postdose treatment. Early intervention reduced the mortality rate in the allyl alcohol plus putrescine group by 20% and by 10% in the carbon tetrachloride as well as the carbon tetrachloride plus putrescine groups. However, the effectiveness of postdose putrescine treatment was less than when putrescine was administered prior to the hepatotoxicant.