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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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Dose-dependent responses to osthole treatment of 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 osthole (Ost) at doses of 0, 0.3, 1, 3, or 10 mg/kg. Data are shown as the mean ± SEM. n = 6 rats in each group. *p<0.05 compared with sham; #p<0.05 compared with T-H + Ost (0 mg/kg).
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pone-0065916-g001: Dose-dependent responses to osthole treatment of 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 osthole (Ost) at doses of 0, 0.3, 1, 3, or 10 mg/kg. Data are shown as the mean ± SEM. n = 6 rats in each group. *p<0.05 compared with sham; #p<0.05 compared with T-H + Ost (0 mg/kg).

Mentions: As shown in Figures 1A and 1B, trauma-hemorrhage was related to a significant increase in plasma AST and ALT levels at 24 h after resuscitation (AST: 2732.0±291.5 vs. 81.5±3.0; ALT: 444.2±74.8 vs. 25.8±6.6 U/ml, p<0.05). Administration of osthole at a dose of 0.3, 1, 3, or 10 mg/kg was used to evaluate the effects of osthole on the attenuation of hepatic injury after trauma-hemorrhage. As shown in Figure 1, there was a diminished benefit when osthole was administered at the dose of 0.3 or 1 mg/kg [AST: 2058.0±216.4 (0.3 mg/kg), 1855.0±334.7 (1 mg/kg); ALT: 359.0±89.5 (0.3 mg/kg), 295.8.0±41.6 (1 mg/kg) U/ml]. The effects of osthole were equivalent when administered at a dose of 3 or 10 mg/kg [AST: 1142.0±255.5 (3 mg/kg), 1118.0±157.7 (10 mg/kg); ALT: 171.3±19.6 (3 mg/kg), 174.8±16.1 (10 mg/kg) U/ml].


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

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

Dose-dependent responses to osthole treatment of 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 osthole (Ost) at doses of 0, 0.3, 1, 3, or 10 mg/kg. Data are shown as the mean ± SEM. n = 6 rats in each group. *p<0.05 compared with sham; #p<0.05 compared with T-H + Ost (0 mg/kg).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065916-g001: Dose-dependent responses to osthole treatment of 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 osthole (Ost) at doses of 0, 0.3, 1, 3, or 10 mg/kg. Data are shown as the mean ± SEM. n = 6 rats in each group. *p<0.05 compared with sham; #p<0.05 compared with T-H + Ost (0 mg/kg).
Mentions: As shown in Figures 1A and 1B, trauma-hemorrhage was related to a significant increase in plasma AST and ALT levels at 24 h after resuscitation (AST: 2732.0±291.5 vs. 81.5±3.0; ALT: 444.2±74.8 vs. 25.8±6.6 U/ml, p<0.05). Administration of osthole at a dose of 0.3, 1, 3, or 10 mg/kg was used to evaluate the effects of osthole on the attenuation of hepatic injury after trauma-hemorrhage. As shown in Figure 1, there was a diminished benefit when osthole was administered at the dose of 0.3 or 1 mg/kg [AST: 2058.0±216.4 (0.3 mg/kg), 1855.0±334.7 (1 mg/kg); ALT: 359.0±89.5 (0.3 mg/kg), 295.8.0±41.6 (1 mg/kg) U/ml]. The effects of osthole were equivalent when administered at a dose of 3 or 10 mg/kg [AST: 1142.0±255.5 (3 mg/kg), 1118.0±157.7 (10 mg/kg); ALT: 171.3±19.6 (3 mg/kg), 174.8±16.1 (10 mg/kg) U/ml].

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