D-galactosamine/lipopolysaccharide-induced hepatotoxicity downregulates sirtuin 1 in rat liver: role of sirtuin 1 modulation in hepatoprotection

Title:

D-galactosamine/lipopolysaccharide-induced hepatotoxicity downregulates sirtuin 1 in rat liver: role of sirtuin 1 modulation in hepatoprotection

Creator:

Kemelo, M. K., Wojnarová, L., Nikolína Kutinová-Canová, and Hassan Farghali

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:cf4e2790-6fd6-4a5d-9152-3393697e88a2
uuid:cf4e2790-6fd6-4a5d-9152-3393697e88a2
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, SIRT1, resveratrol, EX-527, d-galactosamine, lipopolysaccharide, hepatotoxicity, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

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 DGalN/ 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., M. K. Kemelo, L. Wojnarová, N. Kutinová Canová, H. Farghali., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2014 Volume:63 | Number:5

Harvested from:

CDK

Metadata only:

false