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dc.contributor.authorODUAH, I.N.
dc.date.accessioned2018-10-04T13:48:03Z
dc.date.accessioned2019-10-04T10:01:30Z
dc.date.available2018-10-04T13:48:03Z
dc.date.available2019-10-04T10:01:30Z
dc.date.issued1983-05
dc.identifier.urihttps://library.adhl.africa/handle/123456789/12392
dc.descriptionA THESIS IN THE DEPARTMENT OF BIOCHEMISTRY SUBMITTED TO THE COLLEGE OF MEDICINE IN PARTIAL FULFILLMENT OF THE DEGREE OF DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF IBADAN,IBADAN, NIGERIA.en_US
dc.description.abstractSome biochemical interactions of various doses of Niridazole with tissue components have been studied. In-vivo and in-vitro studies with rats have shown that (14C) Niridazole (Anbilhar) 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. The covalent binding was dose-dependent and the greatest amount binding was found in the microsomal fraction. Niridazole also ceased a significant dose dependent decrease in the liver and kidney glutathione levels even though it had no apparent effect on blood glutathione. Alteration of tissue glutathione availability by pre-treatment with chloracetamide or cysteine respectively, increased or decreased respectively, covalent binding of the drug metabolite. Pre-treatment with phenobarbital, 3-methylcholanthrene or cobaltous chloride which change the rate of metabolism of (14C) niridazole similarly altered the extent of protein binding of the radiolabelled substance, while having an opposite effect on the levels of tissue glutathione. The study also indicates that the decrease in tissue glutathione concentration is not due to an effect of the drug on the activity of the glutathione - S - transferases. However, there is a significant reduction in the glutathione reductase activity in all the tissue studied. A comparative study with oxamniquine (mansil) shows that oxamniquine does not bind to tissue DNA and has no effect on liver and kidney glutathione. The conjugation pathways of both drugs, oxamniquine and niridazole were also compared and the conjugates were identified and characterised. Niridazole was found to be excreted as the glutathione, mercapturic acid and glucuronide conjugates while oxamniquine was excreted mainly as the glucuronide and sulphate conjugates. Investigations carried out with mice infected with schistosoma haematobium and treated with Niridazole showed no significant changes in the parameters studied. The possible relationships between the results obtained and the cytotoxic effects of Niridazole and Oxamniquine have been discussed.en_US
dc.language.isoenen_US
dc.subjectBIOCHEMICALen_US
dc.subjectINDUCED TOXICITYen_US
dc.subjectNIRIDAZONEen_US
dc.subjectANBILHARen_US
dc.titleSTUDIES IN POSSIBLE BIOCHEMICAL FACTORS IN NIRIDAZONE (Anbilhar) INDUCED TOXICITYen_US
dc.typeThesisen_US


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