Sirtinol attenuates trauma hemorrhage-induced hepatic injury through Akt-dependent pathway in rats.

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.

• Authors: Fu-Chao Liu, Yung-Fong Tsai, Huang-Ping Yu
• Journal: The journal of trauma and acute care surgery (J Trauma Acute Care Surg) Vol. 74 Issue 4 Pg. 1027-32 (Apr 2013) ISSN: 2163-0763 [Electronic] United States
• PMID: 23511141 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Naphthols
• sirtinol
• Proto-Oncogene Proteins c-akt
• Sirtuins

Topics

• Animals
• Benzamides (pharmacology)
• Blotting, Western
• Disease Models, Animal
• Liver Failure, Acute (drug therapy, enzymology, etiology)
• Male
• Naphthols (pharmacology)
• Proto-Oncogene Proteins c-akt (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Resuscitation
• Shock, Hemorrhagic (drug therapy, enzymology)
• Sirtuins (antagonists & inhibitors)
• Up-Regulation (drug effects)