The cytoprotective effect of a nitric oxide donor drug on gastric mucous membrane of rats treated with ketoprofen, a non-steroidal anti-inflammatory drug.
BACKGROUND
Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent.


OBJECTIVE
To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment.


METHODS
Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration.


RESULTS
a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared to each other.


CONCLUSIONS
Isosorbide dinitrate has a cytoprotective activity on the gastric mucosa of rats submitted to ketoprofen action.
Villa
Afonso Luiz
AL
Divisão de Cirurgia Experimental, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeiro Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Reginaldo
Ceneviva
C
Viaro
Fernanda
F
Ramalho
Fernando
F
Campos
Antonio Dorival
AD
Evora
Paulo Roberto B
PR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects*; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D007660:Ketoprofen / Q000009:adverse effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020030:Nitric Oxide Donors; D008315:Malondialdehyde; D007660:Ketoprofen; D007548:Isosorbide Dinitrate