Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F15%3A43918744" target="_blank" >RIV/00216208:11120/15:43918744 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/15:00448388 RIV/61388980:_____/15:00448388 RIV/00216208:11310/15:10314150 RIV/00216208:11150/15:10314150 RIV/00023001:_____/15:00059555

Result on the web

<a href="https://doi.org/10.1152/ajpgi.00329.2014" target="_blank" >https://doi.org/10.1152/ajpgi.00329.2014</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1152/ajpgi.00329.2014" target="_blank" >10.1152/ajpgi.00329.2014</a>

Result language

angličtina

Original language name

Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation

Original language description

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-alpha, TLR4, IL-1 beta, 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

American Journal of Physiology - Gastrointestinal and Liver Physiology

ISSN

0193-1857

e-ISSN

—

Volume of the periodical

309

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

"G100"-"G111"

UT code for WoS article

000357990800005

EID of the result in the Scopus database

2-s2.0-84937398039