Premium
Melatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal model
Author(s) -
Loots Du Toit,
Wiid Ian J.,
Page Benedict J.,
Mienie Lodewyk J.,
Helden Paul D.
Publication year - 2005
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2004.00176.x
Subject(s) - melatonin , pyrazinamide , isoniazid , antioxidant , hydroxyl radical , radical , chemistry , pharmacology , medicine , rifampicin , biochemistry , antibiotics , tuberculosis , pathology
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 μ g 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.