Effects of naltrexone on lipopolysaccharide-induced sepsis in rats

Shinn Long Lin, Yen Mei Lee, Hsin Yi Chang, Yu Wen Cheng, Mao Hsiung Yen

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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-α 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-α levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.

Original languageEnglish
Pages (from-to)431-440
Number of pages10
JournalJournal of Biomedical Science
Volume12
Issue number2
DOIs
Publication statusPublished - Mar 2005

Keywords

  • Hepatic dysfunction
  • Naltrexone
  • Nitric oxide
  • Reactive oxygen species
  • Sepsis
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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