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Title: Metformin promotes isolated rat liver mitochondria impairment
Authors: Carvalho, Cristina 
Correia, Sónia 
Santos, Maria 
Seiça, Raquel 
Oliveira, Catarina 
Moreira, Paula 
Issue Date: 2008
Citation: Molecular and Cellular Biochemistry. 308:1 (2008) 75-83
Abstract: 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.
DOI: 10.1007/s11010-007-9614-3
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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