Strain Dependant Variation In The Response Of Hepatic Drug Metabolizing Enzymes To Infection With Schistosoma Mansoni.
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Date
2013-03-12
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Abstract
Introduction: Infection with S.mansoni has been shown to alter hepatic drug metabolising enzyme levels in mice although we have shown that hepatic drug metabolising enzymes of male hamsters are not significantly affected as a result of infection. Considerable specie and strain dependent variations do exist, however,' in the pathology of and immune response to S.mansoni infection in animals. It is not known if animals of the same specie but of different strains respond similarly to S.mansoni infection in terms
of their hepatic drug metabolising enzymes. This study was therefore performed to assess the effect of S.mansoni infection on hepatic drug metabolism in vitro in male BALB/c and CBA/H mice.
Results and Discussion: The results in Table 1 show that alterations in hepatic drug metabolism in vitro due to infection with S.mansoni vary between male BALB/c and CBA/H mice. Infected BALB/c and CBA/H mice both showed decreased concentrations of cytochromes P-450 and b5, and a decreased rate of ethoxyresorufin metabolism. Only infected BALB/c mice, however, showed decreases in their NADPHcytochrome c reduce activity and in the rate of ethoxycoumarin metabolism, and an increase in the rate of 4-nitroanisole metabolism. While the microsomal uridine diphosphate glucuronyl transferase
activities were decreased in infected BALB/c and CBA/H mice, the cytosolic glutathione-S-transferase activities were decreased only in BALB/c mice as a result of infection. The reasons for the strain
dependent difference observed here is not known. It is possible that various factors released in the circulation of animals infected with S.mansoni, such as interferons, interleukin-l, histamines etc, affect the activities of hepatic drug metabolising enzymes. Strain dependent alterations in microsomal drug metabolism have also been reported for animals pretreated with inducers of interferon synthesis. Interstrain differences among infected animals in the release of immune modulators such as those described above may be responsible for the varying effects on the hepatic drug metabolizing enzymes and their isozymes.
Conclusions: It is concluded that the disposition of xenobiotics in experimental S.mansoni infected mice will vary depending on the mouse strain being used. Choice of an animal model for studies on the effect of schistosomiasis on drug metabolism should therefore be made carefully especially if extrapolation to humans is intended.
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Presented at the 8th International Symposium on Microsomes and Drug Oxidations in June 1990
Keywords
Schistosoma Mansoni, Enzymes, Drug Metabolism