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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 hepatic IL-6 levels 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 6 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-g005: Effect of osthole treatment on hepatic IL-6 levels 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 6 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: There was no significant difference in hepatic IL-6 levels between the vehicle- and osthole-treated sham groups (Figure 5). Trauma-hemorrhage significantly increased hepatic IL-6 levels in vehicle-treated rats compared with sham animals (776.9±66.1 vs. 89.1±10.1 pg/mg protein, p<0.05). The increase in hepatic IL-6 levels was reduced by osthole treatment, and the osthole-mediated reduction in IL-6 levels was abolished by p38 MAPK inhibitor SB-203580 co-administration [313.3±16.1 (osthole) vs. 764.1±61.8 (osthole + SB-203580) pg/mg protein, 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 hepatic IL-6 levels 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 6 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-g005: Effect of osthole treatment on hepatic IL-6 levels 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 6 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: There was no significant difference in hepatic IL-6 levels between the vehicle- and osthole-treated sham groups (Figure 5). Trauma-hemorrhage significantly increased hepatic IL-6 levels in vehicle-treated rats compared with sham animals (776.9±66.1 vs. 89.1±10.1 pg/mg protein, p<0.05). The increase in hepatic IL-6 levels was reduced by osthole treatment, and the osthole-mediated reduction in IL-6 levels was abolished by p38 MAPK inhibitor SB-203580 co-administration [313.3±16.1 (osthole) vs. 764.1±61.8 (osthole + SB-203580) pg/mg protein, 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