D-galactosamine/lipopolysaccharide-induced hepatotoxicity downregulates sirtuin 1 in rat liver: role of sirtuin 1 modulation in hepatoprotection
Jazyk angličtina Země Česko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24908092
DOI
10.33549/physiolres.932761
PII: 932761
Knihovny.cz E-zdroje
- MeSH
- antioxidancia farmakologie MeSH
- cytoprotekce MeSH
- down regulace MeSH
- galaktosamin * MeSH
- inhibitory enzymů farmakologie MeSH
- játra účinky léků enzymologie patologie MeSH
- karbazoly farmakologie MeSH
- lékové postižení jater enzymologie etiologie patologie prevence a kontrola MeSH
- lipopolysacharidy * MeSH
- modely nemocí na zvířatech MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar MeSH
- resveratrol MeSH
- sirtuin 1 antagonisté a inhibitory metabolismus MeSH
- stilbeny farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide MeSH Prohlížeč
- antioxidancia MeSH
- galaktosamin * MeSH
- inhibitory enzymů MeSH
- karbazoly MeSH
- lipopolysacharidy * MeSH
- resveratrol MeSH
- Sirt1 protein, rat MeSH Prohlížeč
- sirtuin 1 MeSH
- stilbeny MeSH
D-Galactosamine/Lipopolysaccharide (D-GalN/LPS) is a well known model of hepatotoxicity that closely resembles acute liver failure (ALF) seen clinically. The role of sirtuin 1 in this model has not yet been documented. However, there have been a number of studies about the cytoprotective effects of resveratrol, a SIRT1 activator, in the liver. This study was aimed at elucidating the roles of SIRT1 protein expression or catalytic activity in D-GalN/LPS model of hepatotoxicity. ALF was induced in male Wistar rats by intraperitoneal injection of D-GalN and LPS. Some groups of animals were pretreated with resveratrol and/or EX-527 (SIRT1 inhibitor). The effects of these treatments were evaluated by biochemical and Western blot studies. D-GalN/LPS treatment was able to induce hepatotoxicity and significantly increase all markers of liver damage and lipid peroxidation. A dramatic decrease of SIRT1 levels in response to D-GalN/LPS treatment was also documented. Resveratrol pretreatment attenuated D-GalN/LPS-induced hepatotoxicity. EX-527 blocked the cytoprotective effects of resveratrol. However, both resveratrol and EX-527 pretreatments did not exhibit any significant effect on SIRT1 protein expression. Collectively, these results suggest that downregulation of SIRT1 expression is involved in the cytotoxic effects of D-GalN/LPS model and SIRT1 activity contributes to the cytoprotective effects of resveratrol in the liver.
Citace poskytuje Crossref.org
SIRT1 Modulators in Experimentally Induced Liver Injury
