title: Effects of naltrexone on lipopolysaccharide-induced sepsis in rats.
abstract: Naltrexone, an opioid antagonist, has been reported to possess an anti-inflammatory effect via blockade of opioid receptor. The aim of this study is to evaluate the protective effect of naltrexone on LPS-induced septic shock in rats. Sepsis was induced by administration of LPS (10 mg/kg, i.v.) in anesthetized rats. Results demonstrated that pretreatment with naltrexone (10 mg/kg, i.v.) significantly ameliorated hypotension and bradycardia of rats 6 h after LPS administration. In isolated blood vessel, study showed that pretreatment with naltrexone significantly improved norepinephrine-induced vasoconstriction and ACh-induced vasorelaxation in aorta of endotoxemic animals. Naltrexone significantly reduced the elevation of serum glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase (as index of hepatic function) induced by LPS. The infiltration of polymorphonuclear neutrophils into liver 48 h after LPS treatment in mice was also reduced by naltrexone. On the other hand, naltrexone significantly decreased the levels of plasma TNF-alpha and inhibited overproduction of superoxide anions in aortic rings. However, naltrexone did not suppress the overproduction of NO (measured by its metabolites nitrite/nitrate in plasma) and iNOS expression in lungs induced by LPS. In in vitro study, naltrexone did not attenuate non-enzymatic iron-induced lipid peroxidation in rat brain homogenates. In conclusion, pretreatment with naltrexone significantly improved circulatory failure and hepatic dysfunction in sepsis. These effects were associated with reduction of TNF-alpha levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.
authors.affiliation: Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Shinn-Long
authors.initials: SL
authors.lastname: Lin
authors.forename: Yen-Mei
authors.initials: YM
authors.lastname: Lee
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: Mao-Hsiung
authors.initials: MH
authors.lastname: Yen
mesh_terms: D000818:Animals; D000838:Anions; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000473:pathology; D015153:Blotting, Western; D001919:Bradycardia; D019446:Endotoxemia / Q000378:metabolism; D005971:Glutamates / Q000737:chemistry; D006867:Hydrolases / Q000494:pharmacology; D007022:Hypotension; D007501:Iron / Q000737:chemistry; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism; D008099:Liver / Q000293:injuries / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D000637:Transaminases / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000838:Anions; D000975:Antioxidants; D005971:Glutamates; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D009271:Naltrexone; D007501:Iron; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D000637:Transaminases; C022393:phosphoserine aminotransferase; D006867:Hydrolases; C054172:oxaloacetase