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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00064165:_____/17:10361248

Výsledek na webu

<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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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

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Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

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Svazek periodika

66

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

9

Strana od-do

497-505

Kód UT WoS článku

000405692500013

EID výsledku v databázi Scopus

2-s2.0-85026383139