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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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Related in: MedlinePlus

Hepatic p-p38 MAPK and p38 MAPK protein expressions from sham-operated animals receiving vehicle (Sham+Veh; lane 1) or osthole (Sham+Ost; lane 2), trauma-hemorrhage animals receiving vehicle (T-H+Veh; lane 3), osthole (T-H+Ost; lane 4), osthole and SB-203580 (T-H+Ost+SB; lane 5) or SB-203580 (T-H+SB; lane 6).Blots were reprobed for GAPDH as a control for equal protein loading in all lanes. The bands were analyzed using densitometry, and the values are presented as mean ± SEM for 8 rats in each group. *p<0.05 versus all other groups.
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pone-0065916-g006: Hepatic p-p38 MAPK and p38 MAPK protein expressions from sham-operated animals receiving vehicle (Sham+Veh; lane 1) or osthole (Sham+Ost; lane 2), trauma-hemorrhage animals receiving vehicle (T-H+Veh; lane 3), osthole (T-H+Ost; lane 4), osthole and SB-203580 (T-H+Ost+SB; lane 5) or SB-203580 (T-H+SB; lane 6).Blots were reprobed for GAPDH as a control for equal protein loading in all lanes. The bands were analyzed using densitometry, and the values are presented as mean ± SEM for 8 rats in each group. *p<0.05 versus all other groups.

Mentions: There was no significant difference in p38 MAPK protein expression between the sham and trauma-hemorrhaged rats (Figure 6). However, p38 MAPK activity as determined by its phosphorylation was significantly decreased after trauma-hemorrhage (0.27±0.08 vs. 0.73±0.10, p<0.05). Administration of osthole after trauma-hemorrhage restored p38 MAPK activity to the levels observed in the sham animals (0.76±0.12 vs. 0.73±0.10). The increase in phosphorylated-p38 MAPK induced by osthole was abolished when SB-203580 was administered along with osthole [0.19±0.05 (osthole + SB-203580) vs. 0.76±0.12 (osthole), p<0.05] (Figure 6).


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

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

Hepatic p-p38 MAPK and p38 MAPK protein expressions from sham-operated animals receiving vehicle (Sham+Veh; lane 1) or osthole (Sham+Ost; lane 2), trauma-hemorrhage animals receiving vehicle (T-H+Veh; lane 3), osthole (T-H+Ost; lane 4), osthole and SB-203580 (T-H+Ost+SB; lane 5) or SB-203580 (T-H+SB; lane 6).Blots were reprobed for GAPDH as a control for equal protein loading in all lanes. The bands were analyzed using densitometry, and the values are presented as mean ± SEM for 8 rats in each group. *p<0.05 versus all other groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065916-g006: Hepatic p-p38 MAPK and p38 MAPK protein expressions from sham-operated animals receiving vehicle (Sham+Veh; lane 1) or osthole (Sham+Ost; lane 2), trauma-hemorrhage animals receiving vehicle (T-H+Veh; lane 3), osthole (T-H+Ost; lane 4), osthole and SB-203580 (T-H+Ost+SB; lane 5) or SB-203580 (T-H+SB; lane 6).Blots were reprobed for GAPDH as a control for equal protein loading in all lanes. The bands were analyzed using densitometry, and the values are presented as mean ± SEM for 8 rats in each group. *p<0.05 versus all other groups.
Mentions: There was no significant difference in p38 MAPK protein expression between the sham and trauma-hemorrhaged rats (Figure 6). However, p38 MAPK activity as determined by its phosphorylation was significantly decreased after trauma-hemorrhage (0.27±0.08 vs. 0.73±0.10, p<0.05). Administration of osthole after trauma-hemorrhage restored p38 MAPK activity to the levels observed in the sham animals (0.76±0.12 vs. 0.73±0.10). The increase in phosphorylated-p38 MAPK induced by osthole was abolished when SB-203580 was administered along with osthole [0.19±0.05 (osthole + SB-203580) vs. 0.76±0.12 (osthole), p<0.05] (Figure 6).

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