Cirrhosis induced by bile duct ligation alleviates acetic acid intestinal damages in rats: Involvements of nitrergic and opioidergic systems

Pharmacol Rep. 2018 Jun;70(3):426-433. doi: 10.1016/j.pharep.2017.11.010. Epub 2017 Nov 22.


Background: Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats.

Methods: Colitis was induced by acetic acid 28days after bile duct ligation (BDL). L-NAME, as an inhibitor of NO synthase and naltrexone, as an antagonist of opioid receptors were administered intraperitoneally to animals during 3days after induction of colitis. Macroscopic colitis lesion area, inflammatory mediators change, NO metabolite levels, and colon microscopic injuries were assessed 3days after induction.

Results: Cirrhosis significantly reduced the severity of damages to the colon. Administration of L-NAME (10mg/kg), naltrexone (10mg/kg) and co-administration of L-NAME (1mg/kg) and naltrexone (5mg/kg) significantly decreased the protective effect of BDL on colitis. Nitrite elevated levels in BDL rats were significantly diminished in L-NAME- and naltrexone-treated animals. Histopathology parameters and cytokines level alterations in the colon of acetic acid-treated animals after BDL was reversed after injection of L-NAME, naltrexone, and co-administration of L-NAME (1mg/kg) + naltrexone (5mg/kg).

Conclusion: Cirrhosis improved the intestinal damages induced by acetic acid in rats which may be mediated through interaction of nitrergic and opioidergic systems.

Keywords: Bile duct ligation (BDL); Colitis; Nitric oxide; Opioids; Rat.

MeSH terms

  • Acetic Acid / adverse effects*
  • Analgesics, Opioid / pharmacology
  • Animals
  • Bile Ducts / metabolism
  • Bile Ducts / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / physiopathology*
  • Ligation / methods
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / physiopathology*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nitrergic Neurons / drug effects
  • Nitrergic Neurons / metabolism
  • Nitrergic Neurons / physiology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nitrites / pharmacology
  • Opioid Peptides / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / metabolism


  • Analgesics, Opioid
  • Enzyme Inhibitors
  • Narcotic Antagonists
  • Nitrites
  • Opioid Peptides
  • Receptors, Opioid
  • Nitric Oxide
  • Naltrexone
  • Nitric Oxide Synthase
  • Acetic Acid
  • NG-Nitroarginine Methyl Ester