Opioid receptor blockade reduces Fas-induced hepatitis in mice

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Martial JaumeGilles Dietrich

Abstract

Fas (CD95)-induced hepatocyte apoptosis and cytotoxic activity of neutrophils infiltrating the injured liver are two major events leading to hepatitis. Because it has been reported that opioids, via a direct interaction, sensitize splenocytes to Fas-mediated apoptosis by upregulating Fas messenger RNA (mRNA) and modulated neutrophil activity, we assumed that opioids may participate in the pathophysiology of hepatitis. Using the hepatitis model induced by agonistic anti-Fas antibody in mice, we showed that opioid receptor blockade reduced liver damage and consequently increased the survival rate of animals when the antagonist naltrexone was injected simultaneously or prior to antibody administration. Treatment of mice with morphine enhanced mortality. Naloxone methiodide-a selective peripheral opioid antagonist-had a protective effect, but the absence of opioid receptors in the liver, together with lack of morphine effect in Fas-induced apoptosis of primary cultured hepatocytes, ruled out a direct effect of opioids on hepatocytes. In addition, the neutralization of opioid activity by naltrexone did not modify Fas mRNA expression in the liver as assessed with real-time quantitative polymerase chain reaction. Injured livers were i...Continue Reading

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Citations

Nov 24, 2011·Apoptosis : an International Journal on Programmed Cell Death·Sven GottschalkMarc Bilodeau
Sep 27, 2013·Hepatitis Monthly·Ali Dabbagh, Samira Rajaei
Oct 7, 2009·Annals of Plastic Surgery·Behtash Ghazi NezamiAhmad Reza Dehpour
Feb 16, 2010·Life Sciences·Armin Farajzadeh DeroeeAhmad Reza Dehpour
Dec 3, 2015·Current Opinion in Pharmacology·Lilian BassoGilles Dietrich
Jan 29, 2010·The Journal of Investigative Dermatology·Alan BénardGilles Dietrich
May 20, 2008·Journal of Neuroimmunology·Alan BénardGilles Dietrich
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Apr 15, 2021·PloS One·Ling KongJason T Blackard
Jul 25, 2021·International Journal of Molecular Sciences·Xavier Mas-OreaGilles Dietrich

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