Naloxone is protective against indomethacin-induced gastric damage in cholestatic rats

Abstract

We compared indomethacin-induced gastric damage in three groups of rats-bile duct-ligated, sham-operated, and unoperated-and evaluated the role of the opioid system by blocking the effects of endogenous opioids with naloxone. Indomethacin was administered orally in a dose-dependent manner at 10, 30, and 45 mg/ kg. Naloxone was administered intraperitoneally in several doses of 0.5 and 1 mg/kg, starting 30 min before indomethacin (10mg/kg) administration and continued every 30 min. The animals were killed 4h after indomethacin administration. Indomethacin induced more severe gastric damage in bile duct-ligated rats than in sham and unoperated animals, and administration of naloxone (1 mg/kg) every 30 min inhibited the potentiation of indomethacin-induced gastric damage in bile duct-ligated rats, but not in the control groups (sham-operated and unoperated rats). Plasma indomethacin level was also measured, by fluorometry, but showed no significant difference between the groups. Endogenous opioids have been reported to accumulate in plasma of cholestatic animals, and, considering the results of this study, we suggest the opioid system plays an important pathophysiologic role in the pathogenesis of peptic ulcers in cholestatic subjects.

The role of the interaction between endogenous opioids and nitric oxide in the pathophysiology of ethanol‐induced gastric damage in cholestatic rats

“…The protective effect of opioid antagonist administration in production of cholestasis-induced potentiation of gastric damage has been shown previously [5] and the present study replicates this ®nding. With regard to the previous reports that opioids enhance gastric damage induced by gastroinvasive agents [18,27], and with taking into consideration the gastroprotective action of naltrexone in cholestatic rats, we suggest a pathophysiologic role for endogenous opioids in peptic ulcer formation in cholestatic subjects.…”

The Analgesic Effect of Tribulus terrestris Extract and Comparison of Gastric Ulcerogenicity of the Extract with Indomethacine in Animal Experiments

“…The ulcer index was calculated using the J. Score 19,20 . The erosions were classified in size order: 0–1 mm in diameter = 1; 1–2 mm = 2; greater than 2 mm in diameter = 3.…”

Obstructive cholestasis alters intestinal transit in mice: role of opioid system

“…Many important pathophysiologic changes during cholestasis are attributed to this increased opioidergic tone and have been shown to be blocked by administration of opioid receptor antagonists. Precipitation of an opioid withdrawal-like syndrome in patients with cholestasis (Thornton and Losowsky, 1988a) as well as in bile duct-ligated cholestatic mice (Ghafourifar et al, 1997;Dehpour et al, 1998) following injection of an opioid antagonist, alleviation of cholestasis-associated pruritus by administration of naloxone (Bergasa et al, 1995) or naltrexone (Wolfhagen et al, 2000), inhibition by naloxone of cholestasisinduced antinociception in rats (Bergasa et al, 1994), reversal of decreased susceptibility to pentylenetetrazole-induced clonic seizure in mice by naltrexone administration and the naloxone-reversible increase in susceptibility to NSAID-induced gastric ulcer (Dehpour et al, 1999) are among the compatible observations. Accordingly, a global down regulation of Aopioid receptors in the brain of bile duct-ligated rats has been attributed to the increased availability of opioid-agonist ligands at opioid receptors .…”