- 作者: Shyi-Shiaw Jiau; Pao-Yun Cheng; Yen-Mei Lee; Wen-Hsin Huang; Ya-Fang Ko; Mao-Hsiung Yen
- 作者服務機構: 1 Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; ; 2 Department of Pharmacology, National Defense Medical Center, P.O. Box 90048-504 Nei-Hu 114, Taipei, Taiwan; ; 3 Department of Pharmacy, National Defense Medical Center, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Dextromethorphan (DM), an anti-tussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. In our preliminary screening test, LK-4, an analog of DM, can afford more protection against circulatory failure induced by LPS than that of DM. Thus, the aim of this study was to evaluate the effects of LK-4 on sepsis induced by intravenous (i.v.) administration of lipopolysac-charide (LPS; 10 mg/kg) in anesthetized Wistar rats and survival rate by intraperitoneal administration of LPS (70 mg/kg) in conscious ICR mice. Results demonstrated that posttreatment with LK-4 (3 and 5 mg/ kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, LK-4 (3 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-α, as well as values of GOT and GPT, and BUN and creatinine caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by LK-4. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by LK-4. Furthermore, LK-4 increased the survival rate of mice insulted by toxic dose of LPS. In conclusion, the beneficial effects of LK-4 on LPS-induced sepsis result from its antiinflammatory and anti-oxidant effects. Thus, LK-4 can be potentially used as a therapeutic agent for sepsis in the future.
- 中文關鍵字: --
- 英文關鍵字: dextromethorphan, reactive oxygen species, sepsis, TNF-α, nitric oxide, circulatory failure