Journal of Biomedical Science

, Volume 12, Issue 2, pp 431–440

Effects of naltrexone on lipopolysaccharide-induced sepsis in rats

  • Shinn-Long Lin
  • Yen-Mei Lee
  • Hsin-Yi Chang
  • Yu-Wen Cheng
  • Mao-Hsiung Yen
Article

DOI: 10.1007/s11373-005-0647-x

Cite this article as:
Lin, S., Lee, Y., Chang, H. et al. J Biomed Sci (2005) 12: 431. doi:10.1007/s11373-005-0647-x

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.

Keywords

hepatic dysfunctionnaltrexonenitric oxidereactive oxygen speciessepsisTNF-α

Copyright information

© National Science Council, Taipei 2005

Authors and Affiliations

  • Shinn-Long Lin
    • 1
  • Yen-Mei Lee
    • 2
  • Hsin-Yi Chang
    • 3
  • Yu-Wen Cheng
    • 4
  • Mao-Hsiung Yen
    • 2
  1. 1.Department of AnesthesiologyTri-Service General HospitalTaipeiTaiwan
  2. 2.Department of PharmacologyNational Defense Medical CenterTaipeiTaiwan
  3. 3.Department of Pharmacy PracticeTri-Service General HospitalTaipeiTaiwan
  4. 4.Department of PharmacyTaipei Medical UniversityTaipeiTaiwan