| Title | Melatonin prevents the free radical and MADD metabolic profiles induced by antituberculosis drugs in an animal model. | | Author(s) | Loots du T, Wiid IJ, Page BJ, Mienie LJ, van Helden PD | | Institution | Department of Nutrition, School for Physiology, Nutrition and Consumer Science, North-West University, Potchefstroom, South Africa. | | Source | J Pineal Res 2005 Mar; 38(2):100-6. | | MeSH | Animals
Antioxidants
Antitubercular Agents
Carboxylic Acids
Drug Combinations
Free Radicals
Guanine Nucleotide Exchange Factors
Hydroxybenzoic Acids
Isoniazid
Melatonin
Oxidative Stress
Pyrazinamide
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Rifampin
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15683464 |
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