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

《The Chinese Journal of Physiology》 51卷5期 (2008/10) Pp. 292-300

並列摘要

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.

並列關鍵字

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

參考文獻

Ando, H.,Takamura, T.,Ota, T.,Nagai, Y.,Kobayashi, K.(2000).Cerivastatin improves survival of mice with lipopolysaccharideinduced sepsis.J. Pharmacol. Exp. Ther..294,1043-1046.

Angus, D.C.,Linde-Zwirbe, W.T.,Lidicker, J.,Clermont, G.,Carcillo, J.,Pinsky, M.R.(2001).Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care.Crit. Care Med..29,1303-1310.

Beckman, J.S.,Beckman, T.W.,Chert, J.,Marshal1, P.A.,Freeman, B.A.(1990).Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide.Proc. Natl. Acad. Sci. USA.87,1620-1624.

Bone, R.C.,Grodzin, C.J.,Balk, R.A.(1997).Sepsis, a new hypothesis for pathogenesis of the disease process.Chest.112,235-243.

Brix-Christensen, V.,Andersen, S.K.,Andersen, R.,Mengel, A.,Dyhr, T.,Andersen, N.T.,Larsson, A.,Schmitz, O.,Orskov, H.,Tonnesen, E.(2004).Acute hyperinsulinemia restrains endotoxin-induced systemic inflammatory response.Anesthesiology.100,861-870.