Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Drug induced alterations in some rat hepatic microsomal components:a comparative study of four structurally different antimalarials(Pergamon Press, 1985) Thabrew, M.I.; Nashiru, T.O.; Emerole, G.O.Alterations in microsomal drug metabolizing enzymes, microsomal lipids and some serum enzymes following pre-treatment of rats with therapeutic doses of four structurally different antimalarial compounds, chloroquine (CQ), quinine (Q), quinacrine (QK) and primaquine (PQ) have been investigated. CQ and Q significantly decreased the activities of aminopyrene N-demethylase, aniline hydroxylase and both microsomal and cytosolic glutathione S-transferases. Only aniline hydroxylase was markedly decreased by QK, while PQ did not have much effect on any of these enzymes. CQ, Q and QK significantly increased the cholesterol:phospholipid ratio while all four compounds decreased the phosphatidyl choline:sphingomyelin (PC/S) ratio. All the drugs increased the activities of the serum enzymes glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase and alkaline phosphatase. The possible relationships of these results to structural variations in the four drugs being investigated has been discussedItem Covalent binding and glutathione depletion in the rat following niridazole (ambilhar) pretreatment(Springer-Verlag, 1985) Oduah, I.N.; Thabrew, M.I.; Emerole, G.O.In vivo and in vitro studies with rats have shown that (14C) niridazole (Ambilhar) binds covalently to tissue proteins, but not to nucleic acids. In the in vitro experiments, binding required the presence of NADPH in the incubation medium, suggesting the production of an active metabolite via a cytochrome P-450-mediated reaction. Niridazole also caused significant dose-dependent decreases in liver and kidney glutathione levels, even though it had no apparent effect on blood glutathione. Alteration of tissue glutathione availability by pretreatment with chloracetamide or cysteine respectively either increased or decreased the NADPH-dependent covalent binding. Pretreatment with phenobarbital, 3-methylcholanthrene or cobaltous chloride, which change the rate of metabolism of (14C) niridazole, similarly altered the extent of protein binding. It is shown that the decrease in tissue glutathione concentration is not due to an effect of the drug on the activities of either glucose-6-phosphate dehydrogenase or glutathione-S-transferases. However, there is a significant reduction in glutathione reductase activity in all the tissues studied. The possible relationships between the results obtained and the cytotoxic effects of niridazole have been discussed.