Applied Biology and Biochemistry Conference Papers

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Browsing Applied Biology and Biochemistry Conference Papers by Subject "Drug Metabolism"

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    The Effect Of Three Species Of Schistosomes On Hepatic Drug Metabolism In Male BALB/ Mice
    (Elsevier, 1990) Naik, Yogeshkumar S.; Basopo, N.
    Schistosomiasis is a parasitic disease that affects over 200 million people in the world. S.mansoni and S.haematobium are of medical importance while S.mattheei is primarily of veterinary concern. It is important to know the effect that the disease has on elimination of xenobiotics. The effect of S.mansoni infection on thiopental sleeping times and zoxazolamine paralysis times has previously been reported by other workers as well as by us. Similar work on S.mattheei and S.haematobium infected animals, however, has not been reported in the literature. The effect of S.mattheei and S.haematobium on thiopental sleeping times was therefore studied and compared to results obtained for animals infected with S.mansoni. Thiopental sleeping times and egg loads of infected animals are shown in Table 1. Although S.haematobium infected animals did not have detectable levels of parasite eggs in their livers at 8 weeks post-infection, significant numbers of eggs were detectable at 12 weeks post-infection. This is in agreement with the observed delayed maturation of S.haematobium schistosomulae in rodents as compared to S.mansoni or S.mattheei. The number of worm pairs in each group was as follows: S.mattheei 20-25, S.mansoni 8-10, and S.haematobium (both 8 and 12 weeks post infection) 3-10 pairs. The sleeping times of all infected animals were prolonged when compared to their respective controls. The reasons for this are not clear but it is likely that the parasite egg-induced granulomas as well as the physical obstruction to portal blood flow caused by migration of•worms from mesenteric to portal veins play a significant role. Data obtained in this laboratory on drug metabolism in vitro in S.mansoni infected animals indicate that the activity of hepatic drug metabolising enzymes is also altered, but generlllly only in animals that have developed parasite egg-induced granulomas in their livers.
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    Strain Dependant Variation In The Response Of Hepatic Drug Metabolizing Enzymes To Infection With Schistosoma Mansoni.
    (2013-03-12) Naik, Yogeshkumar S.; Hasler, Julia A.
    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.