Sirtuin-Activating Compounds (STACs) Alleviate D-Galactosamine/Lipopolysaccharide-Induced Hepatotoxicity in Rats: Involvement of Sirtuin 1 and Heme Oxygenase 1

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10361248" target="_blank" >RIV/00216208:11110/17:10361248 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/17:10361248

Result on the web

<a href="http://www.biomed.cas.cz/physiolres/pdf/66/66_497.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/66/66_497.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Sirtuin-Activating Compounds (STACs) Alleviate D-Galactosamine/Lipopolysaccharide-Induced Hepatotoxicity in Rats: Involvement of Sirtuin 1 and Heme Oxygenase 1

Original language description

Sirtuin activating compounds (STACs) attenuate various type of liver insults through mechanisms which are not fully understood. In the present study, we investigated the ameliorative potential of quercetin (natural polyphenol) and SRT1720 (synthetic SIRT1 activator) against D-galactosamine/lipopolysaccharide-induced hepatotoxicity (an experimental model of acute liver failure). Moreover, we compared and contrasted the roles of stress responsive enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) in hepatoprotection/hepatotoxicity. Liver injury was induced in male Wistar rats by intraperitoneal injection of D-galactosamine (400 mg/kg) and lipopolysaccharide (10 mu g/kg). Some animals were pretreated with quercetin (50 mg/kg i.p.) or SRT1720 (5 mg/kg i.p.). Twenty-four hours later, the effects of these treatments were evaluated by biochemical studies and Western blot. D-GalN/LPS treatment upregulated HO-1 expression, downregulated SIRT1 expression, decreased AST: ALT ratio and markedly increased bilirubin, catalase and conjugated diene levels. Pretreatment of D-GalN/LPS rats with either quercetin or SRT1720 returned SIRT1 expression, HO-1 expression and all the aforementioned markers towards normal. Collectively, these findings suggest that elevated HO-1 and low SIRT1 expressions are involved in the pathogenesis of D-GalN/LPS-induced hepatotoxicity. Drugs that downregulate HO-1 and/or upregulate SIRT1 seem to have antihepatotoxic effects and need further exploration.

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

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

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Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

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Volume of the periodical

66

Issue of the periodical within the volume

3

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

9

Pages from-to

497-505

UT code for WoS article

000405692500013

EID of the result in the Scopus database

2-s2.0-85026383139