Metformin promotes isolated rat liver mitochondria impairment
Metformin promotes isolated rat liver mitochondria impairment
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DOI：
10.1007/s11010-007-9614-3
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Moreira, Paula I.
中科院分区：
文献类型：
--
作者：
Carvalho, Cristina;Correia, Sonia;Moreira, Paula I.
二甲双胍是一种广泛用于治疗2型糖尿病的药物，最近由于其对线粒体功能的影响的新的和对比的发现而受到关注。在本研究中，我们评估了二甲双胍对离体大鼠肝线粒体状态的影响。我们观察到二甲双胍浓度>= 8 mM可诱导呼吸链受损，其特征为RCR和状态3呼吸降低。然而，仅二甲双胍浓度>= 10 mM通过降低线粒体跨膜电位和增加复极滞后期影响氧化磷酸化系统。此外，我们的研究结果表明，二甲双胍不阻止过氧化氢的产生，也不防止由促氧化剂对ADP/Fe 2+诱导的脂质过氧化。此外，我们观察到二甲双胍通过降低线粒体蓄积Ca 2+的能力和增加巯基的氧化，加剧了Ca 2+诱导的渗透性转换孔开放。综上所述，我们的结果表明二甲双胍可促进肝线粒体损伤，诱发细胞死亡。
Metformin, a drug widely used in the treatment of type 2 diabetes, has recently received attention due to the new and contrasting findings regarding its effects on mitochondrial function. In the present study, we evaluated the effect of metformin in isolated rat liver mitochondria status. We observed that metformin concentrations >= 8 mM induce an impairment of the respiratory chain characterized by a decrease in RCR and state 3 respiration. However, only metformin concentrations >= 10 mM affect the oxidative phosphorylation system by decreasing the mitochondrial transmembrane potential and increasing the repolarization lag phase. Moreover, our results show that metformin does not prevent H2O2 production, neither protects against lipid peroxidation induced by the pro-oxidant pair ADP/Fe2+. In addition, we observed that metformin exacerbates Ca2+-induced permeability transition pore opening by decreasing the capacity of mitochondria to accumulate Ca2+ and increasing the oxidation of thiol groups. Taken together, our results show that metformin can promote liver mitochondria injury predisposing to cell death.