Anti-Inflammatory Effects of LK-3, on LPS-Induced Sepsis in Rats

Wen-Hui Tsai；Pao-Yun Cheng；Yen-Mei Lee；Min-Chen Chiu；Shyi-Shiaw Jiau；Edwin S.C. Wu；Mao-Hsiung Yen

dextromethorphan ； reactive oxygen species ； sepsis ； TNF-α ； nitric oxide ； circulatory failure

The Chinese Journal of Physiology

51卷5期（2008 / 10 / 01）

292 - 300

英文

Dextromethorphan (DM), an antitussive agent, has been shown to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of LK-3, an analog of DM, on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/kg) in anesthetized Wistar rats. Results demonstrated that post-treatment with LK-3 (4 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and bradycardia) in rats treated with LPS. Meanwhile, LK-3 (4 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-α, as well as values of glutamate-oxalacetate transaminase (GOT) and glutamatepyruvate transaminase (GPT) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by post-treatment of LK-3. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by post-treatment with LK-3. In conclusion, the beneficial effects of LK-3 on LPS-induced sepsis resulted from its anti-inflammatory and antioxidant effects.

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