Rebecca Marcelo Alessandro, Ishii-Iwamoto Emy Luiza, Kelmer-Bracht Ana Maria, Caparroz-Assef Silvana Martins, Cuman Roberto Kenji Nakamura, Pagadigorria Clairce Luzia Salgueiro, de Mello João Carlos Palazzo, Bracht Adelar, Bersani-Amado Ciomar Aparecida
Laboratory of Inflammation, Department of Pharmacy and Pharmacology, University of Maringá, Avenida Colombo, 5790, CEP-87020-900, Maringá-Pr, Brazil.
Toxicol Lett. 2003 Jun 5;143(1):55-63. doi: 10.1016/s0378-4274(03)00065-1.
The action of a barbatimão extract on hepatic energy metabolism was investigated using isolated mitochondria and the perfused rat liver. In mitochondria the barbatimão extract inhibited respiration in the presence of ADP and succinate. Stimulation occurred, however, after ADP phosphorylation (state IV respiration). The ADP/O and respiratory control ratios were reduced. The activities of succinate-oxidase, NADH-oxidase and the oxidation of ascorbate were inhibited. The ATPase of intact mitochondria was stimulated, but the ATPases of uncoupled and disrupted mitochondria were inhibited. In perfused livers the extract caused stimulation of oxygen consumption, inhibition of gluconeogenesis and stimulation of glycolysis. Glucose release due to glycogenolysis was stimulated shortly after the introduction of the extract, but inhibition gradually developed as the infusion was continued. Apparently the barbatimão extract impairs the hepatic energy metabolism by three mechanisms: (1) uncoupling of oxidative phosphorylation, (2) inhibition of mitochondrial electron transport, and (3) inhibition of ATP-synthase.
使用分离的线粒体和灌注大鼠肝脏研究了巴巴替昂提取物对肝脏能量代谢的作用。在有ADP和琥珀酸存在的情况下,巴巴替昂提取物抑制线粒体呼吸。然而,在ADP磷酸化后(状态IV呼吸)出现刺激作用。ADP/O和呼吸控制率降低。琥珀酸氧化酶、NADH氧化酶的活性以及抗坏血酸的氧化受到抑制。完整线粒体的ATP酶受到刺激,但解偶联和破碎线粒体的ATP酶受到抑制。在灌注肝脏中,提取物导致耗氧量增加、糖异生受到抑制以及糖酵解受到刺激。引入提取物后不久,糖原分解导致的葡萄糖释放受到刺激,但随着输注的继续,抑制作用逐渐显现。显然,巴巴替昂提取物通过三种机制损害肝脏能量代谢:(1)氧化磷酸化解偶联,(2)抑制线粒体电子传递,以及(3)抑制ATP合酶。