The nitric oxide-cyclic GMP-KATP channels pathway contributes to the effects of montelukast against gastric damage induced by ethanol
The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene receptor, and the involvement of the NO-cGMP-KATP channel pathway was evaluated in gastric damage induced by ethanol in rats. For th...
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Veröffentlicht in: | Alcohol (Fayetteville, N.Y.) N.Y.), 2023-12, Vol.113, p.33-40 |
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Zusammenfassung: | The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene receptor, and the involvement of the NO-cGMP-KATP channel pathway was evaluated in gastric damage induced by ethanol in rats. For this, L-arginine, L-NAME, methylene blue (guanylate cyclase inhibitor), sildenafil, diazoxide, or glibenclamide (ATP-sensitive potassium channel blocker) were administered 30 min before montelukast (0.1, 1, 10, and 20 mg/kg, p.o.). After 1 h, to induce gastric damage, the rats received absolute ethanol (4 ml/kg, p.o.), and then microscopic, macroscopic, and pro-inflammatory parameters (TNF-α and IL-1β) were assessed. Results obtained here revealed that montelukast significantly attenuated the macroscopic and microscopic lesions induced by ethanol. Montelukast also reduced IL-1β and TNF-α levels. It was also observed that NOS inhibitor (L-NAME), methylene blue, and glibenclamide inhibited the effects of montelukast in the stomach. Moreover, the NO precursor (L-arginine), the PDE-5 inhibitor (sildenafil), and a potassium channel opener (diazoxide) before montelukast produced gastroprotective effects. In conclusion, the effect of montelukast against gastric lesions induced by ethanol is mediated, at least in part, through the pathway of the NO-cGMP-KATP channel.
•Montelukast produced gastroprotective effect in ethanol-induced gastric damage.•NO-cGMP-KATP channels pathway have an involvement in the effect of montelukast.•Montelukast attenuated TNF-α and IL-1β levels in ethanol-induced gastric damage.•Montelukast attenuated TNF-α in through the NO-cGMP-KATP channels pathway. |
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ISSN: | 0741-8329 1873-6823 |
DOI: | 10.1016/j.alcohol.2023.05.008 |