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Dextromethorphan prevents circulatory failure in rats with endotoxemia

  • Original Paper
  • Published:
Journal of Biomedical Science

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-α 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.

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Authors and Affiliations

  1. Institute of Toxicology, College of Medicine, National Taiwan University, Taipei

    Hsiao-Ping Wei

  2. Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan, ROC

    Chin-Chen Chu

  3. Department of Pharmacology, National Defense Medical Center, PO Box 90048-504, 114, Neihu Taipei, Taiwan

    Chien-Chuan Wang, Yen-Mei Lee & Mao-Hsiung Yen

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  1. Chien-Chuan Wang
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Wang, CC., Lee, YM., Wei, HP. et al. Dextromethorphan prevents circulatory failure in rats with endotoxemia. J Biomed Sci 11, 739–747 (2004). https://doi.org/10.1007/BF02254358

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  • DOI: https://doi.org/10.1007/BF02254358

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