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, c onsisting 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 physiolo gical human intake) were orally administered to Sprague-Dawley rats. Hydroxyl ra dical production was monitored by quantifying 2,3-dihydroxybenzoic acid produced after intraperitonial sodium salicylate injections. Organic acid extractions an d gas chromatography-coupled mass spectrometry analyses were performed on collec ted urine samples. The results show hydroxyl radicals (P = 0.0019) and organic a cids (P-value range: 0.037 to <0.001), characteristic of a multiple acyl-CoA deh ydrogenase defect (MADD), were elevated with Rifater treatment and these elevati ons 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 b y anti-TB medication indicates inhibition of the electron transport chain. We al so conclude that free radicals leading to clinical symptoms associated with an M ADD metabolic profile induced by anti-TB treatment could be alleviated by melato nin intervention.

Tujuannya adalah untuk mengetahui pengaruh antituberkulosis kombinasi (anti-TB) dan terapi obat antioksidan, melatonin, pada profil asam bebas radikal dan organ ik dalam model tikus percobaan. Sebuah obat anti-TB gabungan, Rifater, terdiri d ari 12,0 mg rifampisin, isoniazid 0,8 mg, dan pirazinamid 23,0 mg dan 18,56 micr og melatonin / kg berat badan per hari (sesuai dengan asupan manusia rata-rata f isiologis) yang diberikan secara oral untuk Sprague Dawley-tikus. Produksi radik al hidroksil dipantau dengan mengukur 2,3-dihydroxybenzoic asam yang dihasilkan setelah suntikan natrium salisilat intraperitonial. Organik asam ekstraksi dan k romatografi gas-coupled massa analisis spektrometri dilakukan pada sampel urin d ikumpulkan. Hasil penelitian menunjukkan radikal hidroksil (P = 0,0019) dan asam organik (P-value range: 0,037 hingga <0,001), karakteristik dari cacat asil-KoA dehidrogenase beberapa (Madd), telah meningkat dengan pengobatan Rifater dan in i peningkatan secara signifikan diturunkan dengan melatonin pretreatment (P-valu e range: 0,031 hingga <0,001), mungkin karena aktivitas antioksidan yang terkand ung di dalamnya. Kami menyimpulkan bahwa produksi radikal hidroksil dan profil a sam organik meningkat disebabkan oleh obat anti-TB menunjukkan penghambatan rant ai transpor elektron. Kami juga menyimpulkan bahwa radikal bebas menyebabkan gej ala klinis yang terkait dengan profil metabolik MADD diinduksi oleh pengobatan a nti-TB dapat diatasi dengan intervensi melatonin.

Melatonin prevents the free radical and MADD metabolic profiles induced by a ntituberculosis drugs in an animal model. Penulis: Loots DT; Wiid IJ; Page BJ; Mienie LJ; van Helden PD Alamat Penulis: Department of Nutrition, School for Physiology, Nutrition and Consumer Scien ce, North-West University, Potchefstroom, South Africa. Sumber:

Journal Of Pineal Research [J Pineal Res] 2005 Mar; Vol. 38 (2), pp. 100-6. Jenis Publikasi: Journal Article; Research Support, Non-U.S. Gov't Bahasa: English Journal Information: Publisher: Munksgaard International Publishers : Copenhagen Country of Publi cation: Denmark NLM ID: 8504412 Publication Model: Print Cited Medium: Print ISS N: 0742-3098 (Print) Linking ISSN: 07423098 NLM ISO Abbreviation: J. Pineal Res. Subsets: MEDLINE