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A Preclinical Model of Exertional Heat Stroke in Mice
Published on: July 1, 2021
Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke
Yi-chang Hsieh1, Ruei-feng Chen, Yi-shian Yeh
1Institute of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan, China.
Acta Pharmacologica Sinica
|February 5, 2011
Summary
Systemic kynurenic acid (KYNA) treatment improved outcomes in heatstroke rats by reducing organ damage and inflammation. KYNA attenuated multiorgan dysfunction, suggesting a potential therapeutic role in managing heatstroke complications.
Area of Science:
- Physiology
- Toxicology
- Pharmacology
Background:
- Heatstroke is a severe condition characterized by hyperthermia and multi-organ dysfunction.
- The pathophysiology involves systemic inflammation, apoptosis, and neuronal damage.
- Current treatments for heatstroke are limited, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the potential therapeutic effects of systemic kynurenic acid (KYNA) administration on heatstroke outcomes in a rat model.
- To assess KYNA's impact on survival, physiological parameters, and cellular damage in various organs during heatstroke.
Main Methods:
- Rats were preconditioned with vehicle or KYNA (30-100 mg/kg) before heat stress induction at 43 °C.
- Physiological parameters (core temperature, mean arterial pressure) were monitored.
- Serum inflammatory markers, hypothalamic neuronal damage, apoptosis in multiple organs (spleen, liver, kidney, lung) were assessed.
Main Results:
- KYNA preconditioning significantly improved survival time in a dose-dependent manner compared to vehicle-treated rats.
- KYNA attenuated hypotension, hypothalamic neuronal degeneration and apoptosis, and multi-organ apoptosis.
- KYNA modulated inflammatory markers, decreasing TNF-α and ICAM-1 while increasing IL-10.
Conclusions:
- Systemic kynurenic acid administration demonstrates protective effects against heatstroke-induced multi-organ dysfunction in rats.
- KYNA may represent a promising therapeutic agent for mitigating the severe consequences of heatstroke.
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