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

Yu HP, Liu FC, Tsai YF, Hwang TL - PLoS ONE (2013)

Bottom Line: These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. yuhp2001@adm.cgmh.org.tw

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 (n = 8 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.

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Effect of osthole treatment on plasma AST (A) and ALT (B) in rats at 24 hours after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H).Animals were treated with either vehicle (Veh), osthole (Ost), osthole in combination with SB-203580 (Ost+SB) or SB-203580 (SB). Data are shown as mean ± SEM of 8 rats in each group. *p<0.05 compared to Sham; #p<0.05 compared to T-H+Veh, T-H+Ost+SB and T-H+SB.
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pone-0065916-g002: Effect of osthole treatment on plasma AST (A) and ALT (B) in rats at 24 hours after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H).Animals were treated with either vehicle (Veh), osthole (Ost), osthole in combination with SB-203580 (Ost+SB) or SB-203580 (SB). Data are shown as mean ± SEM of 8 rats in each group. *p<0.05 compared to Sham; #p<0.05 compared to T-H+Veh, T-H+Ost+SB and T-H+SB.

Mentions: As shown in Figures 2A and 2B, no significant difference in plasma AST and ALT levels was observed between vehicle- and osthole-treated sham groups (AST: 79.0±6.7 vs. 109.7±12.5; ALT: 23.2±2.5 vs. 28.8±4.2 U/ml). At 24 hours after trauma-hemorrhage, there were significant increases in plasma AST and ALT levels. Osthole (3 mg/kg) treatment attenuated the trauma-hemorrhage-induced increase in plasma AST and ALT levels (AST: 1248.0±221.3 vs. 2593.0±321.6; ALT: 193.7±22.8 vs. 490.2±68.9 U/ml, p<0.05). To determine whether the salutary effects of osthole in attenuating hepatic injury after trauma-hemorrhage were mediated via a p38 MAPK-mediated activity, a group of osthole-treated trauma-hemorrhage rats were administrated with the p38 MAPK inhibitor SB-203580. The results indicated that administration of the p38 MAPK inhibitor SB-203580 prevented the osthole-induced decrease in plasma AST and ALT levels [AST: 1248.0±221.3 (osthole) vs. 2541.0±297.3 (osthole + SB-203580); ALT: 193.7±22.8 (osthole) vs. 428.8±60.4.1 (osthole + SB-203580) U/ml, p<0.05].


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

Yu HP, Liu FC, Tsai YF, Hwang TL - PLoS ONE (2013)

Effect of osthole treatment on plasma AST (A) and ALT (B) in rats at 24 hours after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H).Animals were treated with either vehicle (Veh), osthole (Ost), osthole in combination with SB-203580 (Ost+SB) or SB-203580 (SB). Data are shown as mean ± SEM of 8 rats in each group. *p<0.05 compared to Sham; #p<0.05 compared to T-H+Veh, T-H+Ost+SB and T-H+SB.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675024&req=5

pone-0065916-g002: Effect of osthole treatment on plasma AST (A) and ALT (B) in rats at 24 hours after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H).Animals were treated with either vehicle (Veh), osthole (Ost), osthole in combination with SB-203580 (Ost+SB) or SB-203580 (SB). Data are shown as mean ± SEM of 8 rats in each group. *p<0.05 compared to Sham; #p<0.05 compared to T-H+Veh, T-H+Ost+SB and T-H+SB.
Mentions: As shown in Figures 2A and 2B, no significant difference in plasma AST and ALT levels was observed between vehicle- and osthole-treated sham groups (AST: 79.0±6.7 vs. 109.7±12.5; ALT: 23.2±2.5 vs. 28.8±4.2 U/ml). At 24 hours after trauma-hemorrhage, there were significant increases in plasma AST and ALT levels. Osthole (3 mg/kg) treatment attenuated the trauma-hemorrhage-induced increase in plasma AST and ALT levels (AST: 1248.0±221.3 vs. 2593.0±321.6; ALT: 193.7±22.8 vs. 490.2±68.9 U/ml, p<0.05). To determine whether the salutary effects of osthole in attenuating hepatic injury after trauma-hemorrhage were mediated via a p38 MAPK-mediated activity, a group of osthole-treated trauma-hemorrhage rats were administrated with the p38 MAPK inhibitor SB-203580. The results indicated that administration of the p38 MAPK inhibitor SB-203580 prevented the osthole-induced decrease in plasma AST and ALT levels [AST: 1248.0±221.3 (osthole) vs. 2541.0±297.3 (osthole + SB-203580); ALT: 193.7±22.8 (osthole) vs. 428.8±60.4.1 (osthole + SB-203580) U/ml, p<0.05].

Bottom Line: These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. yuhp2001@adm.cgmh.org.tw

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 (n = 8 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.

Show MeSH
Related in: MedlinePlus