Melatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal model

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dc.contributor.authorDu Toit, L.
dc.contributor.authorWiid, I.J.
dc.contributor.authorPage, B.J.
dc.contributor.authorMienie, L.J.
dc.contributor.authorVan Helden, P.D.
dc.contributor.departmentMRC Centre for Molecular and Cellular Biology, of Health Sciences, University of Stellenbosch,PO Box 19063, Tygerberg, 7505, South Africa.en_US
dc.date.accessioned2020-07-03T10:17:07Z
dc.date.available2020-07-03T10:17:07Z
dc.date.epub2005
dc.date.issued2005
dc.description.abstractThe objective was to determine the effect of combined antituberculosis (anti-TB) drug therapy and an antioxidant, melatonin, on the free radical and organic acid profiles in an experimental rat model. A combined anti-TB drug, Rifater, consisting of 12.0 mg rifampicin, 0.8 mg isoniazid, and 23.0 mg pyrazinamide and 18.56 microg melatonin/kg body weight per day (corresponding to average physiological human intake) were orally administered to Sprague-Dawley rats. Hydroxyl radical production was monitored by quantifying 2,3-dihydroxybenzoic acid produced after intraperitonial sodium salicylate injections. Organic acid extractions and gas chromatography-coupled mass spectrometry analyses were performed on collected urine samples. The results show hydroxyl radicals (P = 0.0019) and organic acids (P-value range: 0.037 to <0.001), characteristic of a multiple acyl-CoA dehydrogenase defect (MADD), were elevated with Rifater treatment and these elevations were significantly lowered with melatonin pretreatment (P-value range: 0.031 to <0.001), probably because of its inherent antioxidant activity. We conclude that hydroxyl radical production and an increased organic acid profile induced by anti-TB medication indicates inhibition of the electron transport chain. We also conclude that free radicals leading to clinical symptoms associated with an MADD metabolic profile induced by anti-TB treatment could be alleviated by melatonin intervention.en_US
dc.description.sponsorshipWe thank the National Research Foundation of South Africa for their financial support.en_US
dc.identifier.citationLOOTS DT, WIID IJ, PAGE BJ, MIENIE LJ, VAN HELDEN PD. Melatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal model. Journal of pineal researchen_US
dc.identifier.issn0742-3098.
dc.identifier.journalJournal of pineal researchen_US
dc.identifier.urihttps://infospace.mrc.ac.za/handle/11288/595260
dc.language.isoenen_US
dc.publisherBlackwellen_US
dc.relation.urlhttp://pascal-francis.inist.fr/vibad/index.php?action=search&terms=16476930 .en_US
dc.research.unitClosed Unitsen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectEndocrinologyen_US
dc.subjectBiological and medical sciencesen_US
dc.subjectMedical sciencesen_US
dc.subjectPharmacology. Drug treatmentsen_US
dc.subjectOrganic acidsen_US
dc.subjectAnimalen_US
dc.subjectAntituberculous agenten_US
dc.subjectAnimal modelen_US
dc.subjectDrugen_US
dc.subjectMelatoninen_US
dc.subjectPreventionen_US
dc.subjectFree radicalen_US
dc.subjectRaten_US
dc.subjectorganic acidsen_US
dc.titleMelatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal modelen_US
dc.typeArticleen_US
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