title: Adaptation of rat gastric tissue against indomethacin toxicity.
abstract: Indomethacin is used in the treatment of inflammatory diseases. But the drug toxicity limits its usage. This study investigated whether adaptation occurred after various dosages of repeated (chronic) indomethacin in rats to the gastro-toxic effects of indomethacin. It also examined whether the adaptation was related to oxidant-antioxidant mechanisms and oxidative DNA damage in gastric tissue. To illuminate the adaptation mechanism in the gastric tissue of rats given various dosages of chronic indomethacin, the levels of oxidants and antioxidants (GSH, MDA, NO, SOD and MPO), activities of COX-1 and COX-2 enzymes and oxidative DNA damage (8-OHd Gua/10(5) Gua) were measured. Results were compared to 25-mg/kg single-dose indomethacin group, and the role of oxidant and antioxidant parameters and oxidative DNA damage in the adaptation mechanism was evaluated. The average ulcer areas of gastric tissue of the 0.5-, 1-, 2-, 3-, 4-, and 5-mg/kg dosages of chronic indomethacin given to rats were 19.5+/-3.7, 12.5+/-3.3, 10+/-5.2, 4.5+/-3.6, 8.6+/-2.4, and 9.5+/-2.1mm(2), respectively. This rate was measured as 21.3+/-2.6mm(2) in the single-dose indomethacin group. Consequently, after various dosages of repeated (chronic) indomethacin administration in rats, it was observed that a clear adaptation developed against gastric damage and that gastric damage was reduced. The best adaptation was observed in the gastric tissue of the 3-mg/kg chronic indomethacin group. In parallel with the damage reduction, the oxidant parameters (MDA and MPO) and oxidative DNA damage (8-OHd Gua/10(5) Gua) were reduced, and the antioxidant parameters (GSH, NO and SOD) were increased. There is no relation between COX enzymes and adaptation mechanism. This circumstance shows that not COX-1 and COX-2 enzymes, oxidant and antioxidant parameters may play a role in the adaptation mechanism.
authors.affiliation: Ataturk University, Faculty of Medicine, Department of Pharmacology, Erzurum, Turkey.
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.forename: Halis
authors.initials: H
authors.lastname: Suleyman
authors.forename: Hamit Hakan
authors.initials: HH
authors.lastname: Alp
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects*; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D009569:Nitric Oxide; D008315:Malondialdehyde; D006147:Guanine; D004247:DNA; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D005978:Glutathione; D007213:Indomethacin