Applied Biology and Biochemistry Conference Papers

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Browsing Applied Biology and Biochemistry Conference Papers by Author "Hasler, Julia A."

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    Differential Effects Of Some Quinoline Antimalarial Drugs On Rat Antioxidant Enzyme Activities
    (2013-03-12) Naik, Yogeshkumar S.; Magwere, Tapiwanashe; Hasler, Julia A.
    Quinoline-based antimalarial drugs have played a crucial role in the fight against malaria for decades. However, with the resurgence in drug tolerance among malaria parasites worldwide. The onus is on drug designers to synthesize more effective and less toxic drugs. In this study we sought to determine the effects of quinine, and the synthetic quinolines primaquine and chloroquine, on antioxidant enzymes so as to gain a better understanding of their effects on various enzyme systems which might be of value in the development of new, safe and more effective drugs. We used the Sprague-Dawley rat as a model to study the effects of these drugs on various hepatic and renal antioxidant enzymes. Our results show that primaquine administration increased the activities of some antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase), whereas chloroquine increased the activity of only superoxide dismutase while decreasing that of glutathione peroxidase and catalase. These results indicate a predisposition of the organs towards oxidative damage as evidenced by increases in parameters of lipid peroxidation in the same organs. Unlike the two synthetic drugs, however, quinine did not appear to cause any significant alterations in the activities of the antioxidant enzymes and neither did it cause any oxidative damage in rat organs. From these results, we conclude that since quinoline is still an effective drug against some chloroquine-resistant strains of malaria,the renewed interest in quinoline drugs should aim to design and synthesize quinine analogues which are less toxic and have enhanced antimalarial activity.
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    The Effect of Schistosoma Mansoni Infection on the Hepatic Drug Metabolizing Enzymes of Mice and Hamsters
    (South African Journal of Science, 1998) Naik, Yogeshkumar S.; Hasler, Julia A.
    Discusses the effect of schistosome infection on hepatic drug metabolizing enzymes. Examples of drug metabolizing enzymes; Effect of liver disease of drug metabolism; Alterations in enzyme activity caused by infection; Perturbations in hepatic drug metabolizing enzyme activity with S. mansoni infection.
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    Glutathione Transferase of Schistoma Mansoni and its Interaction with Praziquantel.
    (2013-03-11) Hasler, Julia A.
    Glutathione S-transferases play an important role in the excretion of xenobiotics as well as in the antioxidant defence system of cells. The glutathione S-transferase of the parasitic' trematode Schistosoma mansoni has been studied. The results of preliminary experiments are presented here. The pH optimum of the enzyme was found to be 9.5 which is much higher than that of the mammalian liver enzyme. The apparent Km for the substrate 1 chloro 2,4 dinitrobenzene (CDNBL was 1.25 mN and for glutathione was 0.37 roM. The antischistosomal drug Praziquantel was found to inhibit the conjugation of CDNB in a competitive manner. The implications of these results will be discussed.
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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.