Jacob Molly, Bjarnason Ingvar, Simpson Robert J
Department of Biochemistry, Christian Medical College, Vellore, India 632002.
Clin Sci (Lond). 2002 May;102(5):541-6.
The non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used group of drugs in clinical medicine. However, their propensity to cause gastrointestinal damage limits their clinical utility. The pathogenesis of this toxicity is not well established. It has been postulated that an early event in the development of damage is an effect of these drugs on mitochondrial function. The present paper sets out to evaluate the effects of indomethacin, a commonly used NSAID, on energy metabolism in vivo. Indomethacin was administered to male Sprague-Dawley rats, either intrajejunally or orally, and indices of mitochondrial function were determined. The parameters chosen for this purpose were oxygen uptake by, lactate levels in and the energy charge of jejunal tissue. Oxygen uptake by and energy charge in jejunal tissue were unaffected at 1 and 3 h after dosing by gavage with indomethacin. The drug significantly affected the tissue lactate/pyruvate ratio at 3 h (but not at 1 h) after oral dosing. Effects of indomethacin on jejunum incubated ex vivo were found to be reversible. The data suggest that indomethacin affects mitochondrial function in vivo, but that compensatory changes in glycolytic rate maintain energy charge.
非甾体抗炎药（NSAIDs）是临床医学中广泛使用的一类药物。然而，它们导致胃肠道损伤的倾向限制了其临床应用。这种毒性的发病机制尚未完全明确。据推测，损伤发生早期的一个事件是这些药物对线粒体功能的影响。本文旨在评估常用非甾体抗炎药吲哚美辛对体内能量代谢的影响。将吲哚美辛经空肠内或口服给予雄性Sprague-Dawley大鼠，并测定线粒体功能指标。为此选择的参数是空肠组织的氧摄取量、乳酸水平和能荷。经灌胃给予吲哚美辛后1小时和3小时，空肠组织的氧摄取量和能荷未受影响。口服给药后3小时（而非1小时），该药物显著影响组织乳酸/丙酮酸比值。发现吲哚美辛对离体培养的空肠的作用是可逆的。数据表明，吲哚美辛在体内影响线粒体功能，但糖酵解速率的代偿性变化维持了能荷。
