tailieunhanh - Báo cáo khoa học: Radical-induced oxidation of metformin

Metformin (1,1-dimethylbiguanide) is an antihyperglycae-mic drug used to normalize glucose concentrations in type 2 diabetes. Furthermore, antioxidant benefits have been reported in diabetic patients treated with metformin. This work was aimed at studying the scavenging capacity of this drug against reactive oxygen species (ROS) like Æ OH and O Æ 2 -free radicals. ROS were produced by gamma radio-lysis of water. The irradiated solutions of metformin were analyzed by UV/visible absorption spectrophotometry. It has been shown that hydroxyl free radicals react with met-formin in a concentration-dependent way. . | Eur. J. Biochem. 271 4745-4752 2004 FEBS 2004 doi Radical-induced oxidation of metformin H. Khouri1. F. Collin1 D. Bonnefont-Rousselot2 3 A Legrand2 D. Jore1 and M. Gardes-Albert1 . . . 1 Laboratoire de Chitmie Physique UMR 8601-CNRS Universite Paris 5 France 2Laboratoire de Biochimie Métabolique et Clinique Faculte de Pharmacie Paris 5 France 3Laboratoire de Biochimie B Hopital de la Salpetriere AP-HP Paris France Metformin 1 1-dimethylbiguanide is an antihyperglycae-mic drug used to normalize glucose concentrations in type 2 diabetes. Furthermore antioxidant benefits have been reported in diabetic patients treated with metformin. This work was aimed at studying the scavenging capacity of this drug against reactive oxygen species ROS like OH and O2 -free radicals. ROS were produced by gamma radiolysis of water. The irradiated solutions of metformin were analyzed by UV visible absorption spectrophotometry. It has been shown that hydroxyl free radicals react with metformin in a concentration-dependent way. The maximum scavenging activity was obtained for concentrations of metformin 200 gmol-L-1 under our experimental conditions. An estimated value of 107 L-mol_1-s-1 has been determined for the second order rate constant k OH metformin . Superoxide free radicals and hydrogen peroxide do not initiate any oxidation on metformin in our in vitro experiments. Keywords metformin hydroxyl radical antioxidant radiolysis. Metformin MTF 1 1-dimethylbiguanide see structure in Fig. 1 is one of the most used oral antihyperglycaemic agents. It normalizes plasma glucose concentration without any stimulation of insulin production. It has been demonstrated that elevated glucose levels induce oxidative stress in diabetes . an imbalance between the production of oxidant species particularly radical species and the antioxidant defences 1 . This might partly explain the elevated risk factors for diabetic patients to develop cardiovascular complications

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