Thymohexin exhibits cytoprotective effect in experimental gastric lesions in rats both through the inhibition of inducible nitric oxide synthase and reduction of oxidative mucosal damage

Background and objectiveSome short peptides have recently been reported to exhibit gastroprotective properties but the role of NO-synthase system in these mechanisms still leaves much to be elucidated. That is why the purpose of our study was to explore the gastroprotective effect of the hexapeptide Arg–α-Asp–Lys–Val–Tyr–Arg (thymohexin) under conditions of the modeling of iNOS activity.Materials and methodsThe studies were performed on 80 outbred male rats. Gastric lesions were induced with epinephrine (2 mg/kg) or indomethacin (30 mg/kg). Fifteen minutes before the exposure to ulcerogens rats were pretreated with thymohexin alone and combined with l-arginine or aminoguanidine. Twenty-four hours later gastric mucosa damage, l-arginine/NOS/NO system, processes of lipoperoxidation, superoxide dismutase and catalase activity were assessed.ResultsThymohexin markedly attenuated both epinephrine- and indomethacin-induced gastric ulceration in rats, decreasing the area and score of mucosal lesions (p < 0.05), iNOS activity (p < 0.05) and malonic dialdehyde content (p < 0.05) in gastric mucosa. The cytoprotective effect of thymohexin was significantly enhanced by l-arginine and aminoguanidine. The combination of thymohexin and l-arginine was superior to that with aminoguanidine.ConclusionsThymohexin protects gastric mucosa against epinephrine- and indomethacin-induced gastric lesions in rats. Thymohexin-induced gastroprotection is probably mediated by inhibition of iNOS and decrease of the oxidative damage in gastric mucosa.

► Thymohexin attenuates epinephrine- and indomethacin-induced gastric lesions in rats.
► Thymohexin decreases iNOS activity and lipoperoxidation processes in gastric mucosa.
► Cytoprotective effect of thymohexin is enhanced by l-arginine and aminoguanidine.
► Combination of thymohexin and l-arginine is superior to that with aminoguanidine.
► Thymohexin may be perspective for gastroprotective purposes.