Metformin promotes isolated rat liver mitochondria impairment |
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Authors: | Carvalho Cristina Correia Sónia Santos Maria S Seiça Raquel Oliveira Catarina R Moreira Paula I |
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Institution: | (1) Department of Zoology – Faculty of Sciences and Technology, University of Coimbra, Coimbra, 3000-354, Portugal;(2) Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-517, Portugal;(3) Institute of Physiology – Faculty of Medicine, University of Coimbra, Coimbra, 3000-354, Portugal;(4) Institute of Biochemistry – Faculty of Medicine, University of Coimbra, Coimbra, 3000-354, Portugal |
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Abstract: | 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.
Cristina Carvalho and Sónia Correia contributed equally to this work. |
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Keywords: | Liver Metformin Mitochondria Oxidative phosphorylation system Permeability transition pore Respiratory chain |
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