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Polyamine Protection Against Chemically Induced Hepatotoxicity

Environmental Science PhD Program, School of Science and Technology, Jackson State University, Jackson, Mississippi, USA

Francis E. Chigbo

Department of Chemistry, Jackson State University, Jackson, Mississippi, USA

Harihara M. Mehendale

Department of Toxicology, College of Pharmacy, The University of Louisiana at Monroe, Monroe, Louisiana, USA

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.

Key Words: Biochemical Evaluations • Hepatotoxicity • Histopathological Studies • Intraperitoneal • Liver Enzymes • Polyamine

International Journal of Toxicology, Vol. 19, No. 6, 391-400 (2000)
DOI: 10.1080/109158100750058749


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