N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice.
BACKGROUND
Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment.


METHODS
BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points.


RESULTS
Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05). The levels of portal vein TNF-alpha and plasma ALT increased continuously in the I/R group at 1 and 3 hours of reperfusion compared with the SH group; however, they declined significantly in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved in the I/R-NAC group compared with the I/R group (P<0.05).


CONCLUSIONS
TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.
Jin
Xin
X
Center of Pancreatic Surgery, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Wang
Lin
L
Wu
He-Shui
HS
Zhang
Lei
L
Wang
Chun-You
CY
Tian
Yuan
Y
Zhang
Jing-Hui
JH
D000111:Acetylcysteine / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; D000111:Acetylcysteine