Dextromethorphan prevents circulatory failure in rats with endotoxemia

Abstract

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.

Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

“…ROS are also known to influence the production and secretion of cytokines; after exposure to ROS, DCs more efficiently present antigens [25]. Previous studies have shown that DXM has antioxidant properties in many cell types [16, 19, 35–37]. In this study, we investigated whether DXM could affect ROS formation during the process of LPS-stimulated dendritic cell maturation.…”

“…There is an increasing evidence that DXM has anti-inflammatory and immunomodulatory effects. DXM protects mice against lipopolysaccharide/GalN-induced endotoxemia and liver damage; the mechanism of protection may involve faster TNF- α clearance, decreased superoxide production, and decreased expression of genes associated with inflammation and hepatocellular death [16]. In addition, DXM prevents moderate experimental autoimmune encephalomyelitis by inhibiting the NOX2-mediated production of ROS and decreasing the infiltration of monocytes and lymphocytes into the spinal cord [17].…”

Naltrexone Protects Against Lipopolysaccharide/D-Galactosamine–Induced Hepatitis in Mice

“…Hepatic superoxide anions content was determined by lucigenin-enhanced luminescence as described previously with some modifications (20,21). They were incubated in warmed (37°C), oxygenated (95% O 2 , 5% CO 2 )-equilibrated modified Krebs-HEPES solution containing 20 mM HEPES (pH 7.4) for 30 min.…”

“…Livers were obtained from each group 12 h after the injection of saline, naltrexone, or LPS / D-gal and these tissues were fixed in buffered formaldehyde (10% in phosphate-buffered saline) for histopathological examination as described previously (18,21). The fixed liver tissue were dehydrated in graded ethanol and embedded in paraffin.…”

Biomedical Vignette

“…Wang et al [63] found that DM attenuates the deleterious hemodynamic changes in rats treated with lipopolysaccharides (LPS). DM also inhibits the elevation of plasma tumor necrosis factor-␣ and interleukin-10 levels, and GOT and GPT (index of liver function) or BUN and creatinine (index of renal function) induced by LPS.…”