University of Khartoum

Studies on the Influence of Schistosomiasis and Praziquantel on Hepatic Drug Metabolism in Rabbits

Studies on the Influence of Schistosomiasis and Praziquantel on Hepatic Drug Metabolism in Rabbits

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Title: Studies on the Influence of Schistosomiasis and Praziquantel on Hepatic Drug Metabolism in Rabbits
Author: Wafaa Mohamed Kheir, Kheir
Abstract: The present study aimed at investigation on the effect of infection of rabbits with Schistosoma bovis and praziquantel on the hepatic activities of some drug metabolizing enzymes. Healthy locally bred rabbits were experimentally infected with 600 cercariae of S. bovis by the dermal route to study the effect of experimental schistosomiasis on the activities of aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase enzymes. The experimental infection was confirmed histologically, by detection of S. bovis eggs in the faeces and by measuring the activities of the plasma enzymes, sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) during the course of the disease. The activities of aminopyrine N-demethylase and UDP-glucuronyltransferase significantly decreased by 6, 9 and 13 weeks post infection, while the activity of aniline 4-hydroxylase significantly increased by 9, 13 and 16 weeks post infection. Praziquantel when given orally at the dose rate of 40 mg/kg B.wt resulted in a significant increase in the activities of aminopyrine N-demethylase and aniline 4-hydroxylase in infected animals given the drug 8 and 11 weeks post infection and were respectively killed one and two weeks later. The effect of oral administration of praziquantel at different doses on the drug metabolizing enzyme activities and the lethal dose of praziquantel were also investigated in healthy rabbits. The pathological changes resulting from drug toxicity were histologically assessed by total plasma protein concentration and by measurement of the activities of plasma enzymes. No significant changes were obtained after praziquantel administration at dose levels of 40 mg/kg B.wt and 800 mg/kg B.wt, whereas 1600 mg/kg B.wt and 2000 mg/kg B.wt of praziquantel resulted in a significant decrease in the activities of the three drug metabolizing enzymes under investigation. All rabbits which received praziquantel at the dose rate of 2000 mg/kg B.wt died 10-20 hours following praziquantel administration. Oral administration of dieldrin, a known inducer of drug metabolizing enzymes activity at a dose rate of 2.5 mg/kg B.wt produced no pathological changes in the tissues of treated animals and resulted in the induction of the hepatic activities of the drug metabolizing enzymes aminopyrine N-demethylase and aniline 4-hydroxylase. The induction of these enzymes might have protected rabbits from the lethal effect of praziquantel when given at the dose rate of 2000 mg/kg B.wt ten days following dieldrin pretreatment.
URI: http://khartoumspace.uofk.edu/handle/123456789/14749
Date: 2015-06-24


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