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 objective: Some 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-a-Asp-Lys-Val-Tyr-Arg (thymohexin) under conditions of the modeling of iNOS activity. Materials and methods: The 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. Results: Thymohexin 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. Conclusions: Thymohexin protects gastric mucosa against epinephrine- and indomethacin-induced gastric lesions in rats. Thymohexin-induced gastroprotection is probably mediated by inhibition of INDS and decrease of the oxidative damage in gastric mucosa. (C) 2012 Elsevier B.V. All rights reserved.