HDAC Inhibitors as Epigenetic Regulators

Control rats were conducted by intraperitoneal administration of saline (1 mL/kg) and intraduodenal administration of 0.5% methylcellulose solution. after administration of pilocarpine, compared to control rats. An additional administration of mosapride and rebamipide increased the saliva weight at 0-30 min. The total volume of saliva for 150 min after administration of pilocarpine was the highest after preadministration of rebamipide, followed by mosapride, and risperidone. Conclusions: Increase in salivation produced by i.p. pilocarpine was enhanced by preadministration of rebamipide and mosapride. strong class=”kwd-title” Keywords: pilocalpine- induced salivation, mosapride, rebamipide Introduction Since exposure of the distal esophagus to acid is implicated in elicitation of both symptoms and mucosal damage, the importance of esophageal clearance is generally recognized[1,2]. During esophageal acid clearance, salivation plays an important role in defending the esophageal mucosa[3,4]. It is considered that systemically administered pilocarpine induces the salivary secretion. Additionally, it has been reported that intracerebroventricular injection of pilocarpine also induces salivary secretion in anesthetized rats[5,6]. Takakura et al[7] also demonstrated that the pretreatment with intracerebroventricular injection of atropine inhibited the salivation induced by intraperitoneally administrated pilocarpine, suggesting Indinavir sulfate that the salivary secretion elicited by systemically administered pilocarpine is mediated through the central nervous system as well as through the salivary glands. Many studies suggest that proton pump inhibitors (PPIs) are the most effective medical therapy to control gastro-esophageal reflux disease (GERD) symptoms and heal esophagitis[8,9]. PPIs are the major acid-suppressing drugs used for the treatment of GERD and have better characteristics for the long-term treatment of GERD, because they have a long-lasting, strong effect of raising intragastric pH and have no tachyphylaxis/tolerance phenomena on repeated dosing. However, PPI failure has become more prevalent with the increasing use of PPI as the first-line agent in the treatment of GERD[10]. On the other hand, laryngopharyngeal reflux (LPR) is a major cause of laryngeal inflammation and presents with a constellation of symptoms different from classic gastroesophageal reflux disease. Although LPR is frequently treated with empiric PPIs, most patients require more aggressive and prolonged treatment to achieve regression of symptoms[11]. Mosapride, which has been known to have both a 5-HT4 receptor agonistic and a 5-HT3 antagonist action and to be an agent used in chronic, long-term therapy of GERD was regarded as mediating its efficacy through prokinetic properties. Rebamipide is also widely used as an anti-gastritis and anti-ulcer agent in GERD patients with chronic gastritis. However, these other effects of the study drugs would make these agents even more attractive in the treatment of patients with GERD. Therefore, in the present study, we investigated the effects of rebamipide, mosapride, and risperidone on the salivation induced by pilocarpine. Material & Methods The experiments were conducted on 4-week male SD rats (120-150g). They were maintained under standard animal-housing conditions and had access to water and laboratory pellets except during the experimental period. After a 24-h fast, under urethane anesthesia, a tracheal catheter was put after incising the trachea to secure the airway. Laboratory diet pellets were removed one hour before the measurement of salivary secretion. The salivation was induced by intraperitoneally administrated pilocarpine (0.5 mg/kg of body weight), and saliva was collected using preweighted small cotton balls inserted into the animal’s mouth every 30 min for 180 min. On the day of the experiments, rats were sedated with urethane (1mg/g) intrapertoneally, and kept in lateral decubitus. The cotton ball, 0.5 cm in diameter, was prepared and weighed in an analytic electronic level. The first cotton ball was put under the rat’s tongue. The salivary excretion is determined through the difference in excess weight of the cotton ball before and after collection. The procedure of saliva collection with the cotton ball was carried out at 30-min intervals after pilocarpine was given intraperitoneally. Thirteen moments before intraperitoneal administration of pilocarpine, rebamipide (10mg/kg), mosapride (1mg/kg), and risperidone (1mg/kg) were administered intraduodenally using a metallic tube. Control rats were carried out by intraperitoneal administration of saline (1 mL/kg) and intraduodenal administration of 0.5% methylcellulose solution. Each group consisted of 15 rats. Results Number Indinavir sulfate 1 shows the time-course changes in salivary secretion in four stimulated organizations and unstimulated control group. The salivary excretion was stimulated with intraperitoneal administration of pilocarpine only (pilocarpine group), pilocarpine and risperidone (risperidone.Increase in saliva volume after preadministration of rebamipide and mosapride is the maximum at 60-120 min (176.6% and 173.4%, respectively). the highest after preadministration of rebamipide, followed by mosapride, and risperidone. Conclusions: Increase in salivation produced by i.p. pilocarpine was enhanced by preadministration of rebamipide and mosapride. strong class=”kwd-title” Keywords: pilocalpine- induced salivation, mosapride, rebamipide Intro Since exposure of the distal esophagus to acid is definitely implicated in elicitation of both Indinavir sulfate symptoms and mucosal damage, the importance of esophageal clearance is generally identified[1,2]. During esophageal acid clearance, salivation takes on an important part in defending the esophageal mucosa[3,4]. It is regarded as that systemically given pilocarpine induces the salivary secretion. Additionally, it has been reported that intracerebroventricular injection of pilocarpine also Indinavir sulfate induces salivary secretion in anesthetized rats[5,6]. Takakura et al[7] also shown the pretreatment with intracerebroventricular injection of atropine inhibited the salivation induced by intraperitoneally administrated pilocarpine, suggesting the salivary secretion elicited by systemically given pilocarpine is definitely mediated through the central nervous system as well as through the salivary glands. Many studies suggest that proton pump inhibitors (PPIs) are the most effective medical therapy to control gastro-esophageal reflux disease (GERD) symptoms and heal esophagitis[8,9]. PPIs are the major acid-suppressing drugs utilized for the treatment of GERD and have better characteristics for the long-term treatment of GERD, because they have a long-lasting, strong effect of raising intragastric pH and have no tachyphylaxis/tolerance phenomena on repeated dosing. However, PPI failure has become more prevalent with the increasing use of PPI as the first-line agent in the treatment of GERD[10]. On the other hand, laryngopharyngeal reflux (LPR) is definitely a major cause of laryngeal swelling and presents having a constellation of symptoms different from classic gastroesophageal reflux disease. Although LPR is frequently treated with empiric PPIs, most individuals require more aggressive and long term treatment to accomplish regression of symptoms[11]. Mosapride, which has been known to have both a 5-HT4 receptor agonistic and a 5-HT3 antagonist action and to become an agent used in chronic, long-term therapy of GERD was regarded as mediating its effectiveness through prokinetic properties. Rebamipide is also widely used as an anti-gastritis and anti-ulcer agent in GERD individuals with chronic gastritis. However, these other effects of the study medicines would make these providers even more attractive in the treatment of individuals with GERD. Consequently, in the present study, we investigated the effects of rebamipide, mosapride, and risperidone within the salivation induced by pilocarpine. Material & Methods The experiments were carried out on 4-week male SD rats (120-150g). They were managed under standard animal-housing conditions and had access to water and laboratory pellets except during the experimental period. After a 24-h fast, under urethane anesthesia, a tracheal catheter was put after incising the trachea to secure the airway. Laboratory diet pellets TSPAN3 were removed one hour before the measurement of salivary secretion. The Indinavir sulfate salivation was induced by intraperitoneally administrated pilocarpine (0.5 mg/kg of body weight), and saliva was collected using preweighted small cotton balls inserted into the animal’s mouth every 30 min for 180 min. On the day of the experiments, rats were sedated with urethane (1mg/g) intrapertoneally, and kept in lateral decubitus. The cotton ball, 0.5 cm in diameter, was prepared and weighed in an analytic electronic level. The first cotton ball was put under the rat’s tongue. The salivary excretion is determined through the difference in excess weight of the cotton ball before and after collection. The procedure of saliva collection with the cotton ball was carried out at 30-min intervals after pilocarpine was given intraperitoneally. Thirteen moments before intraperitoneal administration of pilocarpine, rebamipide (10mg/kg), mosapride (1mg/kg), and risperidone (1mg/kg) were administered intraduodenally using a metallic tube. Control rats were carried out by intraperitoneal administration of saline (1 mL/kg) and intraduodenal administration of 0.5% methylcellulose solution. Each group consisted of 15 rats..