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Updated: Jun 5, 2026
Developing a Clinically Relevant Hemorrhagic Shock Model in Rats
Published on: March 22, 2024
Ondansetron attenuates hepatic injury via p38 MAPK-dependent pathway in a rat haemorrhagic shock model
Fu-Chao Liu1, Fu-Wei Liu, Huang-Ping Yu
1Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Background:
Ondansetron is a 5-HT3 receptor antagonist with potent antiemetic, analgesic, and antiphlogistic effects. Recent evidence suggests that the co-existence of 5-HT3 receptors in various cell types is involved in inflammation. However, the effects that 5-HT3 antagonists produce in haemorrhagic shock and resuscitation remain unknown. In this study, we hypothesized that ondansetron administration in male rats, after haemorrhagic shock, decreases cytokine production and protects against hepatic injury through a p38 mitogen-activated protein kinase (MAPK) pathway.
Methods:
Male Sprague-Dawley rats underwent haemorrhagic shock (mean arterial blood pressure 40 mm Hg for 90 min), followed by resuscitation. Various doses of ondansetron (0.1, 0.3, 1, 3 mg kg(-1)) or a single dose of ondansetron (1 mg kg(-1)) with or without a p38 MAPK inhibitor (SB-203580, 2 mg kg(-1)) or vehicle were administered intravenously during resuscitation. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations and various liver proinflammatory parameters were measured at 24h after resuscitation.
Results:
Results show that haemorrhagic shock increases plasma AST and ALT concentrations, hepatic myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels. These parameters were significantly improved in the ondansetron-treated rats subjected to haemorrhagic shock. Ondansetron treatment restored phos-p38 MAPK expression as compared with vehicle-treated haemorrhaged rats. Coadministration of SB-203580 prevented the beneficial effects of ondansetron on postresuscitation proinflammatory responses and hepatic injury.
Conclusion:
Ondansetron attenuates hepatic injury following haemorrhagic shock, which is, at least in part, to be due to its anti-inflammatory effect via p38 MAPK signal pathway.
Insights
Ondansetron reduces liver injury and inflammation after hemorrhagic shock in rats. This protective effect is mediated by the p38 MAPK pathway, highlighting its therapeutic potential.
Area of Science:
- Pharmacology
- Immunology
- Hepatology
Background:
- Ondansetron, a 5-HT3 receptor antagonist, possesses antiemetic, analgesic, and anti-inflammatory properties.
- 5-HT3 receptors are implicated in inflammatory processes.
- The role of 5-HT3 antagonists in hemorrhagic shock and resuscitation is not well understood.
Purpose of the Study:
- To investigate the effects of ondansetron on cytokine production and hepatic injury following hemorrhagic shock in rats.
- To determine if these effects are mediated through the p38 mitogen-activated protein kinase (MAPK) pathway.
Main Methods:
- Male Sprague-Dawley rats experienced hemorrhagic shock (MAP 40 mm Hg for 90 min) followed by resuscitation.
- Rats received various doses of ondansetron, or ondansetron with a p38 MAPK inhibitor (SB-203580) or vehicle.
- Plasma liver enzymes (AST, ALT) and proinflammatory markers were assessed 24 hours post-resuscitation.
Main Results:
- Hemorrhagic shock elevated liver enzymes and proinflammatory markers.
- Ondansetron treatment significantly improved these parameters and restored p38 MAPK expression.
- Inhibiting p38 MAPK abolished the protective effects of ondansetron.
Conclusions:
- Ondansetron attenuates hepatic injury and inflammation post-hemorrhagic shock.
- The anti-inflammatory effect of ondansetron is partly mediated via the p38 MAPK signaling pathway.
