The participation of neutrophils in acute Et/HCl-induced gastric lesions in mice was shown here, as they rapidly accumulated in the injured tissue and neutrophil depletion significantly reduced the injured area. provided by the Central Animal House of the School of Pharmaceutical Science and the Chemistry Institute of the University of S?o Paulo. The animals were housed in standard cages, at room temperature (253C), with 12 h dark/12 h light cycles, and supplemented with food and water LYSO-7 treatment (Figure 2). In addition, we show that the effect of LYSO-7 in Et/HCl-induced gastric lesions is PRKM1 dependent on its PPAR agonist activity, as the protective effect of LYSO-7 in gastric tissue was reversed in mice pre-treated with GW9962, a recognized antagonist of PPAR (Figure 3A and B). Open in a separate window Figure 2 Effects of LYSO-7 treatment on PPAR gene and protein expression in Et/HCl-damaged gastric tissue.Male Swiss mice were treated with CMC (vehicle) or LYSO-7, p.o., 1 hour before oral administration of Et/HCl solution, and gastric tissue was collected 1 hour later. (A) PPAR gene expression and (B and C) PPAR protein expression. Results are expressed as meanSEM LDS 751 of 4 animals in each group. Statistical analysis was performed using ANOVA followed by Tukeys test. *P 0.05 vs. vehicle. Open in a separate window Figure 3 Role of PPAR receptor in the protective effect of LYSO-7 on Et/HCl-induced gastric tissue damage.Male Swiss mice were pretreated with GW9962 or PBS (i.p.) and treated with CMC (vehicle) or LYSO-7 20 min later. Et/HCl solution was administered 1 hour after the treatments. Gastric tissue was collected 1 hour later. (A) shows the percentage of the lesioned area; (B) shows representative images of the gastric tissue. Results are expressed as meanSEM of 5 animals in each group. Statistical analysis was performed using ANOVA followed by Dunnetts test **P 0.01 vs. vehicle. LYSO-7 does not impair acid gastric secretion Data presented in Table 1 show that the pH and H+ concentration in the stomach after pylorus ligation surgery were 3.26 and 135.0, respectively. These values were modified by omeprazole treatment, represented by increased and reduced pH and H+ concentration, respectively. On the other hand, LYSO-7 treatment did not affect gastric secretion parameters. Table 1 Effects of LYSO-7 and omeprazole treatment on biochemical parameters of gastric juice obtained from mice with pylorus ligation. studies had already shown the PPAR pan-agonist activity of LYSO-7 , and here we confirm that the activity is maintained antagonism of the receptor by GW9962 abolished the inhibitory action of LYSO-7 in Et/HCl-induced ulcers. These data corroborate the notion that the isoform seems to be the main class LDS 751 of PPAR in gastric tissue [27C31]. It is worth mentioning that GW9962 has been previously used to determine the PPAR agonistic activity of newly synthesized compounds and to clarify the mechanisms of action of PPAR [45C49]. Neutrophil influx has been observed in several models of gastric ulcers, and they have been thought to act as an inducer of the harmful process [50,51]. The participation of neutrophils in acute Et/HCl-induced gastric lesions in mice was shown here, as they rapidly accumulated in the injured tissue and neutrophil depletion significantly reduced the injured area. Together, these data corroborate the idea that inhibition of neutrophil recruitment may be a target for anti-gastric ulcer therapy [52,53], and that this can be modulated by LYSO-7 treatment. The role of PPAR activation on neutrophil influx has been shown in different models of inflammation, and the majority of them show an inhibitory effect on the process [19,21,54]. The mechanisms involve the direct inhibition of LDS 751 leukocyte-endothelial interactions and chemotaxis [55,56] or impaired chemotactic mediator secretion [57C59]. Our data show, for the first time, that a PPAR agonist affects the trafficking of neutrophils from the bone marrow, as gastric-injured mice pre-treated with LYSO-7 presented higher and lower numbers of neutrophils in the bone marrow and blood, respectively. Our previous results indicate that LYSO-7 may act directly on the locomotory functions of neutrophils. N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP)-induced leukocyte-endothelial interactions in the mesenteric microcirculation are impaired in LYSO-7 treated rats, depending on reduced gene and protein expression of the CD62L and.