Remote ischemic conditioning protects against acetaminophen-induced acute liver injury in mice.
Hepatol Res
; 47(2): 234-245, 2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-26990366
ABSTRACT
AIM:
Acetaminophen (APAP) overdose is a major cause of drug-induced acute liver failure. Studies have shown that remote ischemic pre- and post-conditioning (R-IPC and R-IPOST) can protect the liver against ischemia-reperfusion (I/R) and lipopolysaccharide-induced injuries. The aim of this study was to investigate the effect of R-IPC and R-IPOST on APAP-induced hepatotoxicity in mice.METHODS:
Mice were randomized (n = 6 per group) to seven major groups (i) normal control; (ii) sham operated; (iii) APAP; (iv) R-IPC + APAP; (v) R-IPC + APAP + zinc protoporphyrin (ZnPP); (vi) R-IPOST + APAP; and (vii) R-IPOST + APAP + ZnPP. Sixteen hours after APAP treatment, mouse liver and serum were collected to determine the severity of liver injury.RESULTS:
The results showed that R-IPC and R-IPOST significantly decreased APAP-induced serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-6, and hepatic malondialdehyde, as well as nitrotyrosine formation. Both R-IPC and R-IPOST could improve the hepatic superoxide dismutase, glutathione, and glutathione peroxidase activities and depress the expressions of pro-inflammatory associated proteins, such as inducible nitric oxide synthetase and nuclear factor-κB. They could also increase heme oxygenase-1 expression; however, ZnPP could counteract this protective effect.CONCLUSION:
Remote ischemic conditioning has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting heme oxygenase-1 expression.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article