Bonnefont-Rousselot D, Raji B, Walrand S, Gardès-Albert M, Jore D, Legrand A, Peynet J, Vasson M P
Laboratoire de Biochimie Métabolique et Clinique (EA 3617), Faculté de Pharmacie, Paris, France.
Metabolism. 2003 May;52(5):586-9. doi: 10.1053/meta.2003.50093.
Metformin (dimethylbiguanide) is an antihyperglycemic agent used in type 2 diabetes. Beyond its action on glycemic control, metformin exhibits other intrinsic effects that could play a role in prevention against diabetes complications. Some studies thus reported an improvement in the antioxidant status in patients treated with metformin. This might be in part related to its property to limit formation of advanced glycation end products (AGEs) and to decrease the overproduction of free radicals in diabetic subjects. The aim of this study was to investigate the in vitro ability of metformin to modulate the action of reactive oxygen species (ROS) generated either by water gamma radiolysis or by stimulated human leukocytes. Our results showed that metformin at pharmacologically relevant concentrations was in vitro able to scavenge hydroxyl ((.)OH) but not superoxide (O(.-)(2)) free radicals and that hydrogen peroxide did not react with metformin. Nevertheless, when polymorphonuclear cells (PMN) are stimulated by phorbol myristate acetate (PMA), or above all by formyl methionine leucyl phenylalanine (fMLP), a systematic (although nonsignificant) decrease of the ROS-induced chimiluminescence (CL) was observed. These results suggest that metformin could directly scavenge ROS or indirectly act by modulating the intracellular production of superoxide anion, of which NADPH oxidase constitutes the major source. This could contribute to the additional benefits of metformin, especially those related to the improvement in the cardiovascular outcomes in diabetes.
二甲双胍（二甲基双胍）是一种用于治疗2型糖尿病的降糖药物。除了对血糖控制的作用外，二甲双胍还具有其他内在效应，可能在预防糖尿病并发症方面发挥作用。因此，一些研究报告称，接受二甲双胍治疗的患者抗氧化状态有所改善。这可能部分与其限制晚期糖基化终产物（AGEs）形成以及减少糖尿病患者自由基过度产生的特性有关。本研究的目的是调查二甲双胍在体外调节水γ辐射分解或刺激的人白细胞产生的活性氧（ROS）作用的能力。我们的结果表明，在药理学相关浓度下，二甲双胍在体外能够清除羟基自由基（·OH），但不能清除超氧阴离子自由基（O₂⁻·），并且过氧化氢不与二甲双胍反应。然而，当多形核细胞（PMN）受到佛波酯（PMA）刺激，尤其是受到甲酰甲硫氨酸亮氨酰苯丙氨酸（fMLP）刺激时，观察到ROS诱导的化学发光（CL）有系统性（尽管不显著）降低。这些结果表明，二甲双胍可以直接清除ROS，或者通过调节细胞内超氧阴离子的产生间接发挥作用，其中NADPH氧化酶是主要来源。这可能有助于二甲双胍的额外益处，尤其是那些与改善糖尿病患者心血管结局相关的益处。
