Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion.
OBJECTIVE
To investigate the possible protective effects of carnosol on liver injury induced by intestinal ischemia reperfusion (I/R).


METHODS
Rats were divided randomly into three experimental groups: sham, intestinal I/R and carnosol treatment (n = 18 each). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h. In the carnosol treatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg carnosol 1 h before the operation. At 2, 4 and 6 h after reperfusion, rats were killed and blood, intestine and liver tissue samples were obtained. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and interleukin (IL)-6 were measured. Liver tissue superoxide dismutase (SOD) and myeloperoxidase (MPO) activity were assayed. The liver intercellular adhesion molecule-1 (ICAM-1) and nuclear factor kappaB (NF-kappaB) were determined by immunohistochemical analysis and western blot analysis.


RESULTS
Intestinal I/R induced intestine and liver injury, characterized by histological changes, as well as a significant increase in serum AST and ALT levels. The activity of SOD in the liver tissue decreased after I/R, which was enhanced by carnosol pretreatment. In addition, compared with the control group, carnosol markedly reduced liver tissue MPO activity and serum IL-6 level, which was in parallel with the decreased level of liver ICAM-1 and NF-kappaB expression.


CONCLUSIONS
Our results indicate that carnosol pretreatment attenuates liver injury induced by intestinal I/R, attributable to the antioxidant effect and inhibition of the NF-kappaB pathway.
Yao
Ji-Hong
JH
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China.
Zhang
Xue-Song
XS
Zheng
Shu-Sen
SS
Li
Ying-Hua
YH
Wang
Li-Ming
LM
Wang
Zhen-Zhen
ZZ
Chu
Liang
L
Hu
Xiao-Wei
XW
Liu
Ke-Xin
KX
Tian
Xiao-Feng
XF
D045784:Abietanes / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D018890:Chemoprevention / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
D045784:Abietanes; D015850:Interleukin-6; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; C068623:carnosol; D009195:Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase