Naloxone is protective against indomethacin-induced gastric damage in cholestatic rats.
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.
Dehpour
A R
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Mani
A R
AR
Amanlou
M
M
Nahavandi
A
A
Amanpour
S
S
Bahadori
M
M
D000818:Animals; D002779:Cholestasis / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects* / Q000097:blood; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000150:complications / Q000517:prevention & control*
D009292:Narcotic Antagonists; D009270:Naloxone; D007213:Indomethacin