Browsing by Author "Magwere, Tapiwanashe"

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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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    Effects of chloroquine treatment on antioxidant enzymes in rat liver and kidney.
    (Elsevier Inc., 1996-05-09) Magwere, Tapiwanashe; Naik, Yogeshkumar S.; Hasler, Julia A.
    The effect of chloroquine (CHQ) administration on antioxidant enzymes in rat liver and kidney was studied. Male Sprague-Dawley rats were administered 20 mglkg CHQ once a week for 4 weeks (chronic treatment) or a single dose at 10 or 20 mglkg (acute treatment). Antioxidant enzyme activities were determined in cytosolic fractions of liver and kidney, whereas reduced glutathione (GSH) and malondialdehyde (MDA) were determined in tissue samples. Results indicate minimal effects of acute CHQ treatment, whereas chronic treatment with CHQ differentially affected antioxidant enzymes in the two organs. Superoxide dismutase activity was increased nearly twofold, while activities of selenium glutathione peroxidase (GPX), catalase, and NAD (P) H: quinone oxidoreductase were decreased in livers of CHQ-treated rats compared to controls. No significant effects of CHQ on glutathione reductase, GSH, and MDA levels were seen in the liver. Fewer effects of CHQ were observed in the kidney where a decrease in GPX activity and an increase in MDA levels was seen. Lowering of antioxidant enzymes activities in the liver by CHQ could render the organ more susceptible to subsequent oxidative stress; while increased MDA production after CHQ treatment in the kidney indicate that the organ is being subjected to oxidative stress. This could have implications for prolonged chloroquine intake.
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    Xenobiotic metabolizing enzymes of the freshwater snails.Planorbella and lymnaea (RADIX)Natalensis.
    (J. Med. and Appl. Malacol, 1994) Naik, Yogeshkumar S.; Magwere, Tapiwanashe; Matiyenga, M.; Hasler, Julia A.
    Very little is known about the ability of snails to metabolise and remove xenobiotics such as molluscicides. The present study was conducted to determine whether the freshwater snails Planorbella duryi and Lymnaea (Radix) nntaIensis possess two of the major enzyme systems of detoxication, namely the P450 monooxygenase system and the glutathione Stransferases. We were able to measure microsomal cytochrome b5 and NADPH cytochrome c reductase activity, indicating a functional mixed function oxidase system. However, probing with three known substrates for the mammalian enzyme, we were unable to detect any cytochrome P450 mediated activity. Glutathione Stransferase activity was detectable in cytosolic fractions. In general, the activities detectable in snails were much lower than in mammalian liver preparations. The existence of these enzymes in snails suggests that studies should be undertaken to observe the interaction between these enzymes and xenobiotics such as candidate molluscicides. Key words: Planorbella duyi, Lyrnnaea (Radix) natalensis, cytochrome P450, glutathione