Study of the effect of the opioid antagonist "Naltrexone" on acetic acid-induced enteritis in rats

Abstract

Background: Crohn's disease is a transmural, relapsing inflammatory condition affecting the digestive tract. Opioid signaling was known to affect secretion and motility in the gut and may be implicated in the inflammatory cascade of Crohn's disease. Endogenous Opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. Aim of the study: to detect the possible beneficial effects of opioid antagonist naltrexone in acetic acid-induced enteritis in rats. Animals and Methods: Mature rats are allocated into 9 groups (6 rats each). Enteritis was induced by2trans-rectal injection of acetic acid 4%(2 mg/kg). Salfasalazine (500mg/kg/day), naltrexone (0.05,0.5and one mg/kg/day), and their combination were administered orally from day 1 to day 10. Disease activity index (DAI), biochemical parameters including serum levels of CRP and TNFα, macroscopic and microscopic pathological scores, and in vitro experimental motility studies were used to evaluate the effects of the tested drugs on normal as well as model groups. Results: Induction of enteritis with acetic acid resulted in significant deterioration of DAI, significant elevation of the measured biochemical parameters, and significant deterioration of pathological scores. Treatment with sulfasalazine, low dose of naltrexone, high dose of naltrexone as well as treatment with combination of salfasalazine and naltrexone in both used doses resulted in significant improvement of all measured parameters. Also, Ach-induced contraction of isolated ileal segment showed significant decrease in untreated ones. Conclusion: The results of the present study revealed that naltrexone has the potential to ameliorate the inflammatory response to acetic acid. So opioid antagonist.