Cahova 2016 Am J Physiol Gastrointest Liver Physiol
Cahova M, Palenickova E, Dankova H, Sticova E, Burian M, Drahota Z, Cervinkova Z, Kucera O, Gladkova C, Stopka P, Krizova J, Papackova Z, Oliyarnyk O, Kazdova L (2016) Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation. Am J Physiol Gastrointest Liver Physiol 309:G100-11. |
Cahova M, Palenickova E, Dankova H, Sticova E, Burian M, Drahota Z, Cervinkova Z, Kucera O, Gladkova C, Stopka P, Krizova J, Papackova Z, Oliyarnyk O, Kazdova L (2016) Am J Physiol Gastrointest Liver Physiol
Abstract: Nonalcoholic fatty liver disease is associated with chronic oxidative stress. In our study, we explored the antioxidant effect of antidiabetic metformin on chronic [high-fat diet (HFD)-induced] and acute oxidative stress induced by short-term warm partial ischemia-reperfusion (I/R) or on a combination of both in the liver. Wistar rats were fed a standard diet (SD) or HFD for 10 wk, half of them being administered metformin (150 mgΒ·kg body wt(-1)Β·day(-1)). Metformin treatment prevented acute stress-induced necroinflammatory reaction, reduced alanine aminotransferase and aspartate aminotransferase serum activity, and diminished lipoperoxidation. The effect was more pronounced in the HFD than in the SD group. The metformin-treated groups exhibited less severe mitochondrial damage (markers: cytochrome c release, citrate synthase activity, mtDNA copy number, mitochondrial respiration) and apoptosis (caspase 9 and caspase 3 activation). Metformin-treated HFD-fed rats subjected to I/R exhibited increased antioxidant enzyme activity as well as attenuated mitochondrial respiratory capacity and ATP resynthesis. The exposure to I/R significantly increased NADH- and succinate-related reactive oxygen species (ROS) mitochondrial production in vitro. The effect of I/R was significantly alleviated by previous metformin treatment. Metformin downregulated the I/R-induced expression of proinflammatory (TNF-Ξ±, TLR4, IL-1Ξ², Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers. Our data indicate that metformin reduces mitochondrial performance but concomitantly protects the liver from I/R-induced injury. We propose that the beneficial effect of metformin action is based on a combination of three contributory mechanisms: increased antioxidant enzyme activity, lower mitochondrial ROS production, and reduction of postischemic inflammation. β’ Keywords: 31P MR spectroscopy, Liver injury, Metformin, Mitochondrial respiration, Oxidative stress
β’ O2k-Network Lab: CZ Hradec Kralove Cervinkova Z
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Obesity
Stress:Ischemia-reperfusion, Oxidative stress;RONS
Organism: Rat
Tissue;cell: Liver
Metformin