Anti-inflammatory effects of LK-3, on LPS-induced sepsis in rats.
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-alpha, as well as values of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate 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.
Tsai
Wen-Hui
WH
Division of Genetics and Metabolism, Department of Pediatrics, Chi Mei Foundation Medical Center, Tainan, Taiwan, Republic of China.
Cheng
Pao-Yun
PY
Lee
Yen-Mei
YM
Chiu
Min-Chen
MC
Jiau
Shyi-Shiaw
SS
Wu
Edwin S C
ES
Yen
Mao-Hsiung
MH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003915:Dextromethorphan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019446:Endotoxemia / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009573:Nitrites / Q000097:blood; D051381:Rats; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C028657:3-methoxymorphinan; D003915:Dextromethorphan; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat