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.
Similar content being viewed by others
References
R.L. Barron (1993) ArticleTitleClinical frontiers: pathophysiology of septic shock and implications for therapy Clin. Pharm. 12 829–845 Occurrence Handle1:STN:280:ByuC3c7otFc%3D Occurrence Handle8161370
S. Okusawa J.A. Gelfand T. Ikejima R.J. Connolly C.A. Dinarello (1988) ArticleTitleInterleukin the 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J. Clin Invest. 81 1162–1172 Occurrence Handle1:CAS:528:DyaL1cXhvVCqtLc%3D Occurrence Handle3258319
S. Endo K. Inada H. Nakae (1995) ArticleTitlePlasma levels of type II phospholipase A2 and cytokines in patents with Sepsis. Res. Commun. Mol. Path. Pharmacol. 90 413–421 Occurrence Handle1:CAS:528:DyaK28XislSnsg%3D%3D
Z. Guan L.D. Baier A.R. Morrison (1997) ArticleTitlep38 mitogen-activated protein kinase down-regulates nitric oxide and up-regulates prostaglandin E2 biosynthesis stimulated by interleukin-1β J. Biol Chem. 272 8083–8089 Occurrence Handle10.1074/jbc.272.12.8083 Occurrence Handle1:CAS:528:DyaK2sXitFWrs7k%3D Occurrence Handle9065483
A. Iaz K.P. Chepetial J.H. Korn A.M. Reginato S.A. Jimenez (1998) ArticleTitleDifferential regulation of cyclooxygenase 1 and 2 by interleukin-1B, tumor necrosis factor-α transforming growth factor-B1 in human lung fibroblasts. Exp Cell Rev. 241 222–229 Occurrence Handle10.1006/excr.1998.4050
S. Moncada A. Higgs (1993) ArticleTitleMechanisms of disease the L-arginine-nitric oxide pathway New Engl. J. Med. 329 202–2012 Occurrence Handle10.1056/NEJM199312303292706
E. Abraham (1999) ArticleTitleWhy immunomodulatory therapies have not worked in sepsis Intensive Care Med. 25 556–566 Occurrence Handle10.1007/s001340050903 Occurrence Handle1:STN:280:DyaK1Mzktleitg%3D%3D Occurrence Handle10416906
S. Kayal J.P. Jais N. Aguini J. Chaudiere J. Labrousse (1998) ArticleTitleElevated circulating E-selectin, intracellular adhesion molecule 1 and von Willebrand factor in patients with severe infection. Am. J. Respir. Crit Care Med. 157 776–784 Occurrence Handle1:STN:280:DyaK1c7ns1OltQ%3D%3D Occurrence Handle9517590
C.N. Sessler A.C. Windsor M. Schwartz L. Watson B.J. Fisher B.J. Sugerman A.A. Flowler (1995) ArticleTitleCirculating ICAM-1 is increased in septic shock. Am. J. Respir. Crit Care Med. 151 1420–1427 Occurrence Handle1:STN:280:ByqB2MzlsFQ%3D Occurrence Handle7735595
M.P. Glauser G. Zanetti J.D. Baumgartner J. Cohen (1991) ArticleTitleSeptic shock pathogenesis Lancet 338 732–736 Occurrence Handle10.1016/0140-6736(91)91452-Z Occurrence Handle1:STN:280:By6A28jgt1w%3D Occurrence Handle1679876
A. Goldstin S. Tachibana L.I. Lowney M. Hunkapiller L. Hood (1979) ArticleTitleDynorphin-(1–13) an extraordinarily potent opioid peptide. Proc. Natl. Acad Sci. USA 76 6666–6670 Occurrence Handle230519
A.S. Stern R.V. Lewis S. Kimura J. Rossier L.D. Gerber L. Brink S. Stein S. Udenfriend (1979) ArticleTitleIsolation of the opioid heptapeptide met-enkephalin (Arg6Phe7) from bovine adrenal medullary granules and striatum. Proc. Natl. Acad Sci. USA 76 6680–6683 Occurrence Handle293754
R.C.A. Frederichson (1977) ArticleTitleEnkephalin pentapeptides–a review of current evidence for a physiological role in vertebrate neurotransmission Life Sci. 21 23–41 Occurrence Handle10.1016/0024-3205(77)90421-0 Occurrence Handle18645
T. Hokfelt A. Ljungdahl L. Terenius R. Elde G. Nilsson (1977) ArticleTitleImmunohistochemical analysis of peptide pathways possibly related to pain and analgesia enkephalin and substance P Proc. Natl. Acad. Sci. USA 74 3081–3085 Occurrence Handle1:CAS:528:DyaE2sXltFGlsLY%3D Occurrence Handle331326
C.H. Li (1977) ArticleTitleβ-Endorphin a pituitary peptide with potent morphine-like activity Arch. Biochem. Biophys. 183 592–604 Occurrence Handle10.1016/0003-9861(77)90395-2 Occurrence Handle1:CAS:528:DyaE2sXlsVKjur0%3D Occurrence Handle200175
L. Terenius (1978) ArticleTitleEndogenous peptides and analgesia. Annu. Rev. Pharmacol. Toxicol. 18 189–204 Occurrence Handle1:CAS:528:DyaE1cXksFemu78%3D Occurrence Handle348058
F. Bloom D. Segal N. Ling R. Guillemin (1976) ArticleTitleEndorphins profound behavioral effects in rats suggest new etiological factors in mental illness Science 194 630–632 Occurrence Handle1:CAS:528:DyaE1cXjt1eitQ%3D%3D Occurrence Handle185694
J.W Holaday (1978) ArticleTitleand Faden A.I., Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature 275 450–451 Occurrence Handle1:CAS:528:DyaE1MXhvVSjt74%3D Occurrence Handle357994
J.W. Holaday (1983) ArticleTitleCardiovascular effects of endogenous opiate system. Annu. Rev. Pharmacol Toxicol. 23 541–594 Occurrence Handle1:CAS:528:DyaL3sXktVSmtLg%3D Occurrence Handle6307129
C.H. Baker E.T. Sutton Z Zhou D.G. Reynolds (1990) ArticleTitleReduced microvascular adrenergic receptor activity due to opioids in endotoxin shock. Circulatory Shock 32 101–112 Occurrence Handle1:CAS:528:DyaK3MXhtFKltrg%3D Occurrence Handle2174749
X. Peng D.M. Mosser M.W. Adler T.J. Rogers J.J. Meissler SuffixJr T.K. Eisenstein (2000) ArticleTitleMorphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. J. Leukoc Biol. 68 723–728 Occurrence Handle1:CAS:528:DC%2BD3cXnvF2htbc%3D Occurrence Handle11073113
C.C. Wu C.W. Chiao G. Hsiao A. Chen M.H. Yen (2001) ArticleTitleMelatonin prevents endotoxin-induced circulatory failure in rats. J. Pineal Res. 30 147–156 Occurrence Handle1:CAS:528:DC%2BD3MXitlWjtLk%3D Occurrence Handle11316325
A. Chen W.Y. Chou S.L. Ding M.F. Shaio (1992) ArticleTitleGlomerular localization of nephritogenic protein complex on nonimmunological basis. Lab Invest. 67 175–185 Occurrence Handle1:CAS:528:DyaK3sXltVGk
H.J. Hong S.H. Loh M.H. Yen (2000) ArticleTitleSuppression of the development of hypertension by the inhibitor of inducible nitric oxide synthase. Br. J Pharmacol. 131 631–637 Occurrence Handle1:CAS:528:DC%2BD3cXnsVygur4%3D Occurrence Handle11015317
G. Hsiao C.M. Teng J.R. Sheu Y.W. Cheng K.K. Lam Y.M. Lee T.S. Wu M.H. Yen (2001) ArticleTitleCinnamophilin as a novel antiperoxidative cytoprotectant and free radical scavenger. Biochim Biophys. Acta 1525 1525 77–88 Occurrence Handle1:CAS:528:DC%2BD3MXhtFSrsL4%3D
M. Laubie H. Schmitt M. Vincent G. Remond (1977) ArticleTitleCentral cardiovascular effects of morphinomimetic peptides in dogs. Eur. J Pharmacol. 46 67–71 Occurrence Handle1:CAS:528:DyaE1cXksFCjsQ%3D%3D Occurrence Handle923652
P.M. Almqvist K.M. Knigge M. Kuenzig S.A. Joseph W.H Pilcher S.I. Schwartz (1985) ArticleTitlePulmonary platelet trapping induced by beta-endorphin injection in the cerebrospinal fluid in dogs. Surgy 98 344–349 Occurrence Handle1:CAS:528:DyaL28XitVSmt7s%3D
P.E. Molina (2001) ArticleTitleOpiate modulation of hemodynamic, hormonal, and cytokine responses to hemorrhage. Shock 15 471–478 Occurrence Handle1:STN:280:DC%2BD3MzhtlGltQ%3D%3D Occurrence Handle11386621
K.M. Greeneltch C.C. Haudenschild A.D. Keegan Y. Shi (2004) ArticleTitleThe opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-α production. Brain Behav Immun. 18 476–484 Occurrence Handle1:CAS:528:DC%2BD2cXlvVWit7Y%3D Occurrence Handle15265541
K.D. Horn (1998) ArticleTitleEvolving strategies in the treatment of sepsis and systemic inflammatory response syndrome (SIRS). Quart. J. Med. 91 265–277 Occurrence Handle1:STN:280:DyaK1czjtFGktg%3D%3D
J.S. Beckman T.W. Beckman J. Chen P.A. Marshall B.A. Freeman (1990) ArticleTitleApparent hydroxyl radical production by peroxynitrite Implication for endothelial injury from nitric oxide and superoxide Proc. Natl. Acad. Sci. USA 87 1620–1624 Occurrence Handle1:CAS:528:DyaK3cXhvFegsb4%3D Occurrence Handle2154753
S. Cuzzocrea B. Zingarelli G. Costantino A. Sottile D. Teti A.P. Caputi (1999) ArticleTitleProtective effect of poly (ADP-ribose) synthetase inhibition on multiple organ failure after zymosan-induced peritonitis in the rat. Crit Care Med. 27 1517–1523 Occurrence Handle1:STN:280:DyaK1Mzpslelsg%3D%3D Occurrence Handle10470759
D.T. Lysle T. How (1999) ArticleTitleEndogenous opioids regulate the expression of inducible nitric oxide synthase by splenocytes. J. Pharmacol. Exp Ther. 288 502–508 Occurrence Handle1:CAS:528:DyaK1MXpvFOhsA%3D%3D Occurrence Handle9918551
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11373-005-0647-x