Nazareth W M, Sethi J K, McLean A E
Department of Clinical Pharmacology, University College London, U.K.
Biochem Pharmacol. 1991 Jul 25;42(4):931-6. doi: 10.1016/0006-2952(91)90055-a.
The effect of paracetamol on mitochondrial function was studied using rat liver slices. Changes in the potential of the mitochondrial and plasma membrane were monitored using [3H]-triphenylmethylphosphonium (TPMP+) and [14C]thiocyanate (SCN-) probes, respectively. Liver slices were exposed to 10 mM paracetamol for various time periods (0-360 min) after loading with TPMP+. The release of TPMP+ which correlates with a decrease in the mitochondrial membrane potential became significant after 30 min incubation with 10 mM paracetamol. The change in the mitochondrial membrane potential was shown to be independent of cytochrome P450 activity. No significant change in plasma membrane potential was observed, until the release of lactate dehydrogenase (LDH) had begun, 4 hr after exposure, reflecting the ultimate stages of cell injury by paracetamol. These results suggest that paracetamol elicits a direct effect on the mitochondrial function before cell injury develops and adds further evidence to the role of mitochondria in paracetamol toxicity.
使用大鼠肝切片研究了对乙酰氨基酚对线粒体功能的影响。分别使用[³H] - 三苯基甲基鏻（TPMP⁺）和[¹⁴C]硫氰酸盐（SCN⁻）探针监测线粒体膜电位和质膜电位的变化。在用TPMP⁺加载后，将肝切片暴露于10 mM对乙酰氨基酚不同时间段（0 - 360分钟）。与线粒体膜电位降低相关的TPMP⁺释放，在与10 mM对乙酰氨基酚孵育30分钟后变得显著。线粒体膜电位的变化显示与细胞色素P450活性无关。直到暴露4小时后乳酸脱氢酶（LDH）开始释放，质膜电位才观察到显著变化，这反映了对乙酰氨基酚导致细胞损伤的最终阶段。这些结果表明，对乙酰氨基酚在细胞损伤发生之前就对线粒体功能产生直接影响，并为线粒体在对乙酰氨基酚毒性中的作用提供了进一步的证据。
