Dextromethorphan prevents circulatory failure in rats with endotoxemia
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Published on: April 26, 2015
Chien-Chuan Wang1, Yen-Mei Lee, Hsiao-Ping Wei
1Department of Pharmacology, National Defense Medical Center, Taipei, ROC.
Abstract:
Dextromethorphan (DM), an antitussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of DM on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS) in anesthetized Wistar rats and by intraperitoneal administration in conscious ICR mice. Results demonstrated that pretreatment with DM (1, 5 and 10 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, DM (5 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha and interleukin-10 levels, as well as values of GOT and GPT (as an index of liver function), and BUN and creatinine (as an index of renal function) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by DM. Moreover, infiltration of neutrophils into the lungs and liver of rats 6 h after treatment with LPS was also reduced by DM. In conclusion, the beneficial effects of DM on LPS-induced sepsis result from its anti-inflammatory and antioxidant effects. Thus, DM can possibly be used as a prophylactic agent for sepsis in the future.
Insights
Dextromethorphan (DM) shows promise in treating sepsis. This antitussive agent reduced harmful inflammation and improved organ function in animal models, suggesting its potential as a future sepsis prophylactic.
Area of Science:
- Pharmacology
- Immunology
- Sepsis Research
Background:
- Dextromethorphan (DM), primarily an antitussive, exhibits in vitro anti-inflammatory and immunomodulatory properties.
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
Purpose of the Study:
- To investigate the in vivo effects of Dextromethorphan (DM) on sepsis induced by lipopolysaccharide (LPS) in rodent models.
- To evaluate DM's potential as a prophylactic agent against sepsis-induced organ damage and inflammation.
Main Methods:
- Sepsis was induced in Wistar rats and ICR mice using lipopolysaccharide (LPS).
- Dextromethorphan (DM) was administered intravenously as a pretreatment.
- Hemodynamic parameters, plasma cytokine levels (TNF-α, IL-10), liver and renal function markers (GOT, GPT, BUN, creatinine), nitric oxide (NO) production, inducible NO synthase (iNOS) expression, and neutrophil infiltration were assessed.
Main Results:
- DM pretreatment significantly attenuated LPS-induced hypotension and tachycardia in rats.
- DM inhibited the elevation of pro-inflammatory cytokines (TNF-α) and modulated anti-inflammatory cytokines (IL-10).
- DM improved liver and renal function, reduced NO and superoxide anion overproduction, and decreased neutrophil infiltration in lung and liver tissues.
Conclusions:
- Dextromethorphan (DM) demonstrates significant anti-inflammatory and antioxidant effects in LPS-induced sepsis models.
- These findings suggest that DM possesses protective properties against sepsis-induced organ damage.
- DM holds potential as a future prophylactic agent for sepsis treatment.
