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Updated: May 13, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Sirtinol attenuates trauma hemorrhage-induced hepatic injury through Akt-dependent pathway in rats
Fu-Chao Liu1, Yung-Fong Tsai, Huang-Ping Yu
1Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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.
Insights
Sirtinol protects against liver injury following trauma hemorrhage by activating the Akt pathway. This study demonstrates sirtinol
Area of Science:
- Biomedical research
- Pharmacology
- Hepatology
Background:
- Sirtinol exhibits anti-inflammatory and protective effects in shock states.
- The precise mechanism underlying sirtinol's protective actions remains unclear.
- Akt (protein kinase B) is known to mediate anti-inflammatory responses during injury.
Purpose of the Study:
- To investigate the role of Akt in sirtinol's attenuation of hepatic injury after trauma hemorrhage.
- To elucidate the molecular pathway involved in sirtinol's hepatoprotective effects.
Main Methods:
- Male Sprague-Dawley rats underwent trauma hemorrhage and resuscitation.
- Sirtinol was administered with or without the PI3K inhibitor wortmannin.
- Hepatic injury markers, including plasma transaminases and myeloperoxidase activity, were assessed 24 hours post-resuscitation.
Main Results:
- Trauma hemorrhage significantly elevated liver injury markers.
- Sirtinol treatment markedly improved these markers and increased hepatic phospho-Akt expression.
- Co-administration of wortmannin negated the protective effects of sirtinol, indicating Akt pathway involvement.
Conclusions:
- Sirtinol demonstrates a protective effect against hepatic injury induced by trauma hemorrhage.
- This protective effect is mediated, at least in part, through an Akt-dependent pathway.
- The findings highlight a potential therapeutic role for sirtinol in managing trauma-hemorrhage-induced liver injury.
