Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26045616
DOI
10.1152/ajpgi.00329.2014
PII: ajpgi.00329.2014
Knihovny.cz E-zdroje
- Klíčová slova
- 31P MR spectroscopy, liver injury, metformin, mitochondrial respiration, oxidative stress,
- MeSH
- adenosintrifosfát metabolismus MeSH
- antiflogistika farmakologie MeSH
- antioxidancia farmakologie MeSH
- apoptóza účinky léků MeSH
- časové faktory MeSH
- cytoprotekce MeSH
- dieta s vysokým obsahem tuků MeSH
- energetický metabolismus účinky léků MeSH
- jaterní mitochondrie účinky léků metabolismus patologie MeSH
- játra účinky léků metabolismus patologie MeSH
- mediátory zánětu metabolismus MeSH
- metformin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- nealkoholová steatóza jater farmakoterapie etiologie metabolismus patologie MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- reperfuzní poškození etiologie metabolismus patologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfát MeSH
- antiflogistika MeSH
- antioxidancia MeSH
- mediátory zánětu MeSH
- metformin MeSH
- reaktivní formy kyslíku MeSH
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 mg·kg body wt(-1)·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-α, TLR4, IL-1β, 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.
Clinical and Transplant Pathology Department Charles University Prague Czech Republic;
Department of Chemistry University of Cambridge Cambridge United Kingdom; and
Institute of Inorganic Chemistry Academy of Science CR Husinec Rez Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic;
Citace poskytuje Crossref.org
