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Sirtinol attenuates trauma hemorrhageinduced hepatic injury through Akt-dependent pathway in rats

Liu, Fu-Chao MD, PhD; Tsai, Yung-Fong MD; Yu, Huang-Ping MD, PhD

Journal of Trauma and Acute Care Surgery:
doi: 10.1097/TA.0b013e3182858389
Original Articles
Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Author Information

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: yuhp2001@adm.cgmh.org.tw.

© 2013 Lippincott Williams & Wilkins, Inc.