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

Du Toit, L.
Wiid, I.J.
Page, B.J.
Mienie, L.J.
Van Helden, P.D.
The 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.
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Endocrinology,Biological and medical sciences,Medical sciences,Pharmacology. Drug treatments,Organic acids,Animal,Antituberculous agent,Animal model,Drug,Melatonin,Prevention,Free radical,Rat,organic acids
LOOTS 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 research
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