Dextromethorphan prevents circulatory failure in rats with endotoxemia.
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-alpha 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.
Wang
Chien-Chuan
CC
Department of Pharmacology, National Defense Medical Center, Taipei, ROC.
Lee
Yen-Mei
YM
Wei
Hsiao-Ping
HP
Chu
Chin-Chen
CC
Yen
Mao-Hsiung
MH
D000818:Animals; D001775:Blood Circulation / Q000502:physiology*; D015153:Blotting, Western; D003915:Dextromethorphan / Q000494:pharmacology*; D019446:Endotoxemia / Q000188:drug therapy*; D004926:Escherichia coli / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000378:metabolism; D009566:Nitrates / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000737:chemistry; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis; D013481:Superoxides / Q000737:chemistry; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016753:Interleukin-10; D009569:Nitric Oxide; D003915:Dextromethorphan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D010100:Oxygen