Protective effects of pretreatment with oleanolic acid in rats in the acute phase of hepatic ischemia-reperfusion injury: role of the PI3K/Akt pathway.
Oleanolic acid (OA) has been used to treat liver disorders, but whether it can attenuate hepatic ischemia-reperfusion- (IR-) associated liver dysfunction remains unexplored. In the present study, 160 male Sprague-Dawley rats were equally divided into five groups: group SH received neither hepatic IR nor drugs; group IR received hepatic IR without drugs; group CM and group OA received 0.5% sodium carboxymethylcellulose and 100 mg/kg OA, intragastrically, once a day for seven days before the hepatic IR, respectively; on the basis of treatment in group OA, group OA+wortmannin further received 15 μg/kg of PI3K inhibitor wortmannin, intraperitoneally, 30 min before the hepatic IR. Then each group was equally divided into four subgroups according to four time points (preoperation, 0 h, 3 h, and 6 h after reperfusion). Serum ALT activity, IL-1β concentration, and hepatic phosphorylation of PI3K, Akt, and GSK-3β protein expression were serially studied. We found that OA pretreatment improved histological status and decreased serum ALT and IL-1β levels. It also increased p-PI3K, p-Akt, and p-GSK-3β protein expression at all the four time points. Prophylactic wortmannin partially reversed OA's protective effects. The data indicate that OA pretreatment protects liver from IR injury during the acute phase partially through PI3K/Akt-mediated inactivation of GSK-3β.
Department of Anesthesiology, 1st Affiliated Hospital, Nanjing Medical University, Nanjing, China ; Key laboratory of Anesthesiology, Xuzhou, Jiangsu, China.
Bo
B
Gui
Department of Anesthesiology, 2rd Affiliated Hospital, Nanchang University, Nanchang, China.
Fuzhou
F
Hua
Department of Emergency, 1st Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Jie
J
Chen
Department of Anesthesiology, Jiangsu Tumor Hospital, Nanjing, China.
Zeping
Z
Xu
Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, Nanjing, China.
Hongbin
H
Sun
Department of Anesthesiology, 1st Affiliated Hospital, Nanjing Medical University, Nanjing, China ; Key laboratory of Anesthesiology, Xuzhou, Jiangsu, China.
Yanning
Y
Qian
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002266:Carboxymethylcellulose Sodium / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009828:Oleanolic Acid / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D053583:Interleukin-1beta; D009828:Oleanolic Acid; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D002266:Carboxymethylcellulose Sodium; D000077191:Wortmannin