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Effects of naltrexone on lipopolysaccharide-induced sepsis in rats

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Journal of Biomedical Science

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.

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Authors and Affiliations

  1. Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan

    Shinn-Long Lin

  2. Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan

    Yen-Mei Lee & Mao-Hsiung Yen

  3. Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan

    Hsin-Yi Chang

  4. Department of Pharmacy, Taipei Medical University, Taipei, Taiwan

    Yu-Wen Cheng

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  1. Shinn-Long Lin
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  2. Yen-Mei Lee
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  3. Hsin-Yi Chang
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  4. Yu-Wen Cheng
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  5. Mao-Hsiung Yen
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Correspondence to Mao-Hsiung Yen.

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Lin, SL., Lee, YM., Chang, HY. et al. Effects of naltrexone on lipopolysaccharide-induced sepsis in rats. J Biomed Sci 12, 431–440 (2005). https://doi.org/10.1007/s11373-005-0647-x

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  • DOI: https://doi.org/10.1007/s11373-005-0647-x

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