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Osthole attenuates hepatic injury in a rodent model of trauma-hemorrhage.

Abstract
Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (nā€Š=ā€Š8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.
AuthorsHuang-Ping Yu, Fu-Chao Liu, Yung-Fong Tsai, Tsong-Long Hwang
JournalPloS one (PLoS One) Vol. 8 Issue 6 Pg. e65916 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23755293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Coumarins
  • Imidazoles
  • Interleukin-6
  • Pyridines
  • Intercellular Adhesion Molecule-1
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • osthol
Topics
  • Alanine Transaminase (metabolism)
  • Animals
  • Aspartate Aminotransferases (metabolism)
  • Coumarins (therapeutic use)
  • Hemorrhage (drug therapy, metabolism)
  • Imidazoles (pharmacology)
  • Intercellular Adhesion Molecule-1 (metabolism)
  • Interleukin-6 (metabolism)
  • Liver (drug effects, injuries, metabolism)
  • Male
  • Pyridines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Wounds and Injuries (drug therapy, metabolism)
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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