title: Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers.
abstract: Indomethacin is an indol derivative, non-steroidal, anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. Indomethacin became the first-choice drug to produce an experimental ulcer model as a result of having a higher ulcerogenic potential than other non-steroidal anti-inflammatory drugs (NSAIDs). There have been several conflicting reports about the ulcerogenic mechanism of indomethacin; the mechanism is still unclear. It has been suggested that indomethacin induces gastric damage via inhibiting the release of protective factors like cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2), bicarbonate, and mucus; increasing aggressive factors like acid; and increasing oxidant parameters while decreasing antioxidant parameters. Classic antiulcer drugs are known to produce antiulcer effects by activating against indomethacin (increasing PGE2, mucus, and bicarbonate production; inhibiting acid secretion; decreasing oxidant parameters; and increasing antioxidants). However, some antiulcer drugs have been shown to inhibit indomethacin-induced ulcers without affecting acid and mucus secretion or oxidant parameters, as well as to inhibit the production of protective factors like COX-1, PGE2, and bicarbonate, and to reduce antioxidant parameters. In order to resolve the contradictions in the abovementioned data, this review hypothesized a relationship between indomethacin-induced ulcers and alpha 2 adrenergic receptors. It is suggested that blockage of alpha 2 adrenergic receptors may be responsible for the increase in the aggressive factors induced by indomethacin, and stimulation of alpha 2 adrenergic receptors may be responsible for the increase of protective factors induced by antiulcer drugs.
authors.affiliation: Faculty of Medicine, Department of Pharmacology, Ataturk University, Erzurum, Turkey. suleyman@atauni.edu.tr
authors.forename: Halis
authors.initials: H
authors.lastname: Suleyman
authors.forename: Abdulmecit
authors.initials: A
authors.lastname: Albayrak
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bilici
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001639:Bicarbonates / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D008954:Models, Biological; D009093:Mucus / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D018341:Receptors, Adrenergic, alpha-2; D009569:Nitric Oxide; D015232:Dinoprostone; D007213:Indomethacin