Caparroz-Assef S M, Bersani-Amado C A, do Nascimento E A, Kelmer-Bracht A M, Ishii-Iwamoto E L
Laboratory of Liver Metabolism and Biological Oxidations, University of Maringá, Brazil.
Res Commun Mol Pathol Pharmacol. 1998 Jan;99(1):93-116.
The effects of nimesulide on energy metabolism and the hepatic metabolic alterations produced by adjuvant-induced arthritis were investigated in the perfused rat liver an in isolated liver mitochondria. Nimesulide, at therapeutic levels (20-50 microM), produced: (1) stimulation of oxygen consumption in the perfused rat liver and in isolated mitochondria, (2) inhibition of gluconeogenesis; (3) reduction of ADP/O ratio and the respiratory control ratio and stimulation of glycogenolysis in the livers from healthy rats, but not in livers from arthritic rats. These results indicate that nimesulide acts as a mitochondrial uncoupler. The main alterations produced by adjuvant-induced arthritis were: higher rates of oxygen consumption in both perfused livers and isolated mitochondria, with no decrease in the efficiency of mitochondrial energy transduction; (2) decreased gluconeogenesis and lack of glycogenolytic response to uncouplers, but not to alpha 1-agonists. These data allow to conclude that nimesulide-induced impairment of energy metabolism should worsen the hepatic disturbances that are already associated with the adjuvant disease.
在灌注大鼠肝脏和分离的肝线粒体中研究了尼美舒利对佐剂诱导性关节炎所致能量代谢及肝脏代谢改变的影响。治疗剂量（20 - 50微摩尔）的尼美舒利可产生：（1）刺激灌注大鼠肝脏和分离线粒体中的氧消耗；（2）抑制糖异生；（3）降低健康大鼠肝脏中的ADP/O比值和呼吸控制率并刺激糖原分解，但对关节炎大鼠肝脏无此作用。这些结果表明尼美舒利作为一种线粒体解偶联剂发挥作用。佐剂诱导性关节炎产生的主要改变为：灌注肝脏和分离线粒体中的氧消耗率均较高，线粒体能量转导效率无降低；（2）糖异生减少且对解偶联剂而非α1 - 激动剂缺乏糖原分解反应。这些数据可以得出结论，尼美舒利诱导的能量代谢损害应会加重已与佐剂性疾病相关的肝脏紊乱。
