Recent evidences show that sirtinol possesses anti-inflammatory properties and protective effects after shocklike states, but the mechanism of these effects remains unknown. Akt (also known as protein kinase B) exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether Akt plays any role in the sirtinol-mediated attenuation of hepatic injury after trauma hemorrhage.
Male Sprague–Dawley rats underwent trauma hemorrhage (mean blood pressure maintained at approximately 35–40 mm Hg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of sirtinol (1 mg/kg i.v.) with and without a PI3K inhibitor wortmannin (1 mg/kg i.v.), wortmannin, or vehicle was administered. Plasma alanine aminotransferase with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats per group) at 24 h after resuscitation. One-way analysis of variance and Tukey testing were used for statistical analysis.
Trauma hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 levels, and plasma alanine aminotransferase and aspartate aminotransferase concentrations. These parameters were significantly improved in the sirtinol-treated rats subjected to trauma hemorrhage. Sirtinol treatment also increased hepatic phospho-Akt expression compared with vehicle-treated trauma-hemorrhaged rats. The coadministration of wortmannin with sirtinol abolished the sirtinol-induced beneficial effects on the above parameters and hepatic injury.
These results suggest the protective effect of sirtinol administration on the alleviation of hepatic injury after trauma hemorrhage, which is, at least in part, through Akt-dependent pathway.
From the Department of Anesthesiology (F-C.L., Y-F.T., H-P.Y.), Chang Gung Memorial Hospital; College of Medicine (F-C.L., Y-F.T., H-P.Y.), Chang Gung University; and Graduate Institute of Clinical Medical Sciences (Y-F.T.), Chang Gung University, Taoyuan, Taiwan.
Submitted: November 14, 2012, Revised: December 25, 2012, Accepted: December 26, 2012.
This work was partially supported by the National Science Council (grant no. NSC101-2314-B-182A-010) and the Chang Gung Memorial Hospital (grant nos. CMRPG381073 and CMRPG3B1051) to Huang-Ping Yu. Support was also provided by the National Science Council (grant no. NSC101-2314-B-182-082) and the Chang Gung Memorial Hospital (grant no. CMRPG3B1621) to Fu-Chao Liu.
Address for reprints: Huang-Ping Yu, MD, PhD, Department of Anesthesiology, Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan 333; email: firstname.lastname@example.org.