The cytoprotective effect of a nitric oxide donor drug on gastric mucous membrane of rats treated with ketoprofen, a non-steroidal anti-inflammatory drug

Abstract

-Background -Non-steroidal anti-infl ammatory 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 benefi cial 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-infl ammatory 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. Aim -To defi ne a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-infl ammatory 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 sacrifi ced 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 signifi cant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically signifi cant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical signifi cance when compared to each other. Conclusion -Isosorbide dinitrate has a cytoprotective activity on the gastric mucosa of rats submitted to ketoprofen action.

Gastroprotective Effects of L‐Lysine Salification of Ketoprofen in Ethanol‐Injured Gastric Mucosa

“…Conflicting results are reported in the literature as to the role of NO in NSAIDs induced gastrotoxicity. While some studies suggest the clear ability to revert gastric mucous membrane alterations (Kato et al, ; Villa et al, ), other studies link NOSII expression and consequent NO overproduction to the development of gastrointestinal inflammatory disorders. A general interpretation of the above results is that physiological NO concentration, regulated by the NOSI enzymatic expression, is key in maintaining the gastric mucous membrane function, whereas NO overproduction by NOSII expression would result in a cytotoxic activity possibly mediated by oxygen free radicals (Calatayud et al, ).…”

Curcumin ameliorates diclofenac sodium‐induced nephrotoxicity in male albino rats

“…Anti‐inflammatory chemotherapeutics are commercially categorized into steroidal and nonsteroidal (nonsteroidal anti‐inflammatory drugs; NSAIDs) . The exact mechanism of action of NSAIDs is not known but it is probably related to the decrease in the fatty acid entering the cell or released from the cell .…”

Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor

“…The NO levels are slightly elevated in vardenafil pretreated rats in our study; however, the level of NO in either of vardenafil groups did not surpass the level of NO determined in the sham group. Some studies revealed gastroprotective effects of some agents without significant alterations in NO or MDA levels [31] . Determination of tissue cGMP level was not included in our study design.…”