Mechanism of salutary effects of astringinin on rodent hepatic injury following trauma-hemorrhage: Akt-dependent hemeoxygenase-1 signaling pathways.

Abstract

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35-40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation.

• Authors: Fu-Chao Liu, Tsong-Long Hwang, Ying-Tung Lau, Huang-Ping Yu
• Journal: PloS one (PLoS One) Vol. 6 Issue 10 Pg. e25907 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22022464 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL1
• Chemokine CXCL2
• Cxcl1 protein, rat
• Cxcl2 protein, rat
• Interleukin-6
• Stilbenes
• Intercellular Adhesion Molecule-1
• 3,3',4,5'-tetrahydroxystilbene
• Peroxidase
• Heme Oxygenase-1
• Aspartate Aminotransferases
• Alanine Transaminase
• Proto-Oncogene Proteins c-akt

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Chemokine CXCL1 (metabolism)
• Chemokine CXCL2 (metabolism)
• Heme Oxygenase-1 (metabolism)
• Hemorrhage (blood, complications, drug therapy, enzymology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-6 (metabolism)
• Liver (drug effects, enzymology, injuries)
• Male
• Peroxidase (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Stilbenes (pharmacology, therapeutic use)
• Wounds and Injuries (blood, complications, drug therapy, enzymology)