Selective COX-2 inhibition is associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis.
OBJECTIVE
To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits.


METHODS
Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30 mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h).


RESULTS
Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis.


CONCLUSIONS
COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin. Treatment with the COX-2 inhibitor DFU is associated with improvement of mucosal damage, which may have therapeutic implications.
Lanas
Angel
A
Service of Digestive Diseases, Unit of Gastrointestinal Research, University Hospital, Unidad Mixta de Investigación, Zaragoza, Spain.
Jiménez
Pilar
P
Ferrández
Angel
A
Escartín
Alfredo
A
Arenas
Juan
J
Esteva
Francisco
F
Ortego
Javier
J
D000143:Acids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004941:Esophagitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D009061:Mouth Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010434:Pepsin A / Q000008:administration & dosage / Q000494:pharmacology; D010894:Piroxicam / Q000008:administration & dosage / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000032:analysis; D011817:Rabbits
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D000143:Acids; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D011453:Prostaglandins; D010894:Piroxicam; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010434:Pepsin A; D007213:Indomethacin