Related Experiment Videos
Attenuating heat-induced acute lung inflammation and injury by dextromethorphan in rats
Hsi-Hsing Yang1, Ching-Cheng Hou, Mao-Tsun Lin
1Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai., Yongkang District, Tainan City 710, Taiwan. jessica@mail.stut.edu.tw
Abstract:
Dextromethorphan (DM) has been shown to protect against endotoxic shock in mice. Heatstroke resembles sepsis in many respects. The objective of this study was to examine the heat-induced acute lung inflammation and injury in rats with or without DM, and for comparison with those of the rats with MK-801 (an N-methyl-D-aspartate receptor antagonist), SA4503 (a sigma-1 receptor agonist), or fluoxetine (a serotonin reuptake inhibitor). Heatstroke was induced by exposing the anesthetized rats to heat stress (43°C for 68 min). At 68 minutes after start of heat stress, animals treated with vehicle medium, DM (10-30 mg/kg of body weight, intramuscular), MK-801 (1 mg/kg of body weight, intraperitoneal), SA4503 (1 mg/kg of body weight, intraperitoneal), or fluoxetine (5 mg/kg of body weight, intraperitoneal) were allowed to recover at room temperature (26°C). As compared with vehicle-treated heatstroke rats (25-31 min; n = 8), DM (30 mg/kg)-treated heatstroke rats and MK-801 (1 mg/kg)-treated heatstroke rats had significantly greater survival time (193-209 min [n = 7] and 121-133 min [n = 8], respectively). However, the survival times for the SA4503-treated heatstroke rats (28-34 min; n = 8) or the fluoxetine-treated heatstroke rats (20-26 min; n = 8) were not significantly different from the vehicle-treated heatstroke rats. DM treatment significantly: (1) reduced acute lung injury, including edema, neutrophils infiltration, and hemorrhage scores; (2) decreased acute pleurisy; and (3) decreased bronchoalveolar fluid levels of the proinflammatory cytokines, and ischemia and oxidative damage markers during heatstroke. Our results indicate that DM therapy may improve outcomes of heatstroke in rats by antagonizing the N-methyl-D-aspartate receptors.
Insights
Dextromethorphan (DM) significantly improved survival and reduced lung injury in heatstroke rats, suggesting N-methyl-D-aspartate receptor antagonism as a therapeutic target for heatstroke.
Area of Science:
- Physiology
- Pharmacology
- Toxicology
Background:
- Heatstroke shares similarities with sepsis, a condition where Dextromethorphan (DM) has shown protective effects.
- Acute lung inflammation and injury are critical complications of heatstroke.
Purpose of the Study:
- To investigate the efficacy of Dextromethorphan (DM) in mitigating heat-induced acute lung inflammation and injury in a rat model.
- To compare DM's effects with other receptor modulators: MK-801 (NMDA antagonist), SA4503 (sigma-1 agonist), and fluoxetine (serotonin reuptake inhibitor).
Main Methods:
- Heatstroke was induced in rats by exposure to 43°C for 68 minutes.
- Animals were treated with vehicle, DM, MK-801, SA4503, or fluoxetine post-heat stress.
- Survival time, lung injury scores, pleurisy, bronchoalveolar fluid cytokines, and oxidative stress markers were assessed.
Main Results:
- DM (30 mg/kg) significantly increased survival time (193-209 min) compared to vehicle controls (25-31 min).
- DM treatment markedly reduced lung edema, neutrophil infiltration, hemorrhage, and pleurisy.
- DM decreased pro-inflammatory cytokines and markers of ischemia and oxidative damage in bronchoalveolar fluid.
Conclusions:
- Dextromethorphan therapy demonstrates significant therapeutic potential in improving outcomes for heatstroke in rats.
- The protective effects of DM appear to be mediated through the antagonism of N-methyl-D-aspartate receptors.
