title: Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage.
abstract: Mechanisms of gastric defence under conditions of combined influence of acute stress and non-steroidal anti-inflammatory drugs (NSAIDs) are still poorly studied. The aim of this study was to explore the effects of different types of NSAIDs (naproxen, celecoxib and ATB-346) in producing experimental gastric lesions (induced by water-restraint stress (WRS) or by epinephrine (EPN) injection) and to determine the role of lipid peroxidation and the nitric oxide (NO) system in the pathogenesis of the damage. Male rats were used (eight per group) in this work. The NSAIDs were all administered at a dose 10 mg kg(-1) 30 min prior to WRS or EPN injection. Administration of naproxen to the control rats caused development of gastric lesions, whereas administration of a hydrogen sulfide (H2S)-releasing NSAID (ATB-346) or a selective cyclooxygenase-2 inhibitor (celecoxib) did not cause gastric damage. In contrast, lipid peroxidation processes were enhanced in all groups as was the activity of NO synthase (NOS). Pretreatment with naproxen in the WRS model caused an increase in severity of damage and a decrease in NOS activity. ATB-346 displayed beneficial effects, manifested by a decrease in the area of gastric damage, but parameters of lipid peroxidation and the NOS system did not differ substantially from those in the group treated with naproxen. Administration of different NSAIDs under conditions of EPN-induced gastric damage resulted in the decrease in NOS activity and lipid peroxidation. None of the tested NSAIDs exacerbated EPN-induced gastric mucosal injury; indeed, they all reduced the extent of damage.
authors.affiliation: Biochemistry Department, Danylo Halytsky Lviv National Medical University , Lviv , Ukraine and.
authors.forename: Iryna
authors.initials: I
authors.lastname: Fomenko
authors.forename: Alexander
authors.initials: A
authors.lastname: Sklyarov
authors.forename: Tetyana
authors.initials: T
authors.lastname: Bondarchuk
authors.forename: Lilya
authors.initials: L
authors.lastname: Biletska
authors.forename: Natalia
authors.initials: N
authors.lastname: Panasyuk
authors.forename: John L
authors.initials: JL
authors.lastname: Wallace
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D000068579:Celecoxib; D004195:Disease Models, Animal; D004837:Epinephrine; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009288:Naproxen / Q000031:analogs & derivatives / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011720:Pyrazoles / Q000633:toxicity; D017208:Rats, Wistar; D012149:Restraint, Physical; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013315:Stress, Psychological / Q000150:complications*; D013449:Sulfonamides / Q000633:toxicity
chemical_list: C550692:2-(6-methoxy-napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D011720:Pyrazoles; D013449:Sulfonamides; D009569:Nitric Oxide; D009288:Naproxen; D019001:Nitric Oxide Synthase; D000068579:Celecoxib; D004837:Epinephrine; D006862:Hydrogen Sulfide
keywords: Hydrogen sulphide; NSAIDs; lipid peroxidation; naproxen; nitric oxide; peptic ulcer