Burcham P C, Harman A W
Department of Pharmacology, Queen Elizabeth II Medical Centre, University of Western Australia, Nedlands.
Toxicol Lett. 1990 Jan;50(1):37-48. doi: 10.1016/0378-4274(90)90250-p.
The effect of paracetamol intoxication on mitochondrial function was studied in isolated mouse hepatocytes. Inhibition of cellular respiration as well as a lowering of cellular ATP contents and ATP/ADP ratios was associated with exposure to toxic concentrations of paracetamol. Significantly, inhibition of 3-hydroxybutyrate- and lactate/pyruvate-supported respiration, as well as the reduction in cellular ATP levels and ATP/ADP ratios, preceded the appearance of plasma membrane damage, as assessed by LDH leakage. N-Acetylcysteine reduced the extent of plasma membrane damage induced by paracetamol and protected against the impairment of cellular respiration. This suggests that respiratory dysfunction was a consequence of the oxidation of paracetamol to its reactive metabolite within the liver cell. These findings indicate that paracetamol toxicity results in an impairment of mitochondrial function which precedes the loss of plasma membrane integrity.
在分离的小鼠肝细胞中研究了对乙酰氨基酚中毒对线粒体功能的影响。细胞呼吸抑制以及细胞ATP含量和ATP/ADP比值降低与暴露于毒性浓度的对乙酰氨基酚有关。值得注意的是，通过乳酸脱氢酶（LDH）泄漏评估，在质膜损伤出现之前，3-羟基丁酸酯和乳酸/丙酮酸支持的呼吸受到抑制，以及细胞ATP水平和ATP/ADP比值降低。N-乙酰半胱氨酸减少了对乙酰氨基酚诱导的质膜损伤程度，并防止细胞呼吸受损。这表明呼吸功能障碍是肝细胞内对乙酰氨基酚氧化为其活性代谢物的结果。这些发现表明，对乙酰氨基酚毒性导致线粒体功能受损，这先于质膜完整性的丧失。
