Investigating the pharmacological potential of phytol on experimental models of gastric ulcer in rats.

Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50 mg/kg, administered orally 1 h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25 mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5 mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100 mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.

Exercise and pyridostigmine prevents gastric emptying delay and increase blood pressure and cisplatin-induced baroreflex sensitivity in rats.

Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces improves in the autonomic nervous system. In the current study, we investigated the effect of physical exercise and pyridostigmine treatment on gastrointestinal and cardiovascular changes in cisplatin-treated rats. Rats were divided into groups: Saline (S), Cisplatin (Cis), Exercise (Ex), Cisplatin+Exercise (Cis+Ex), Pyridostigmine (Pyr), and Cisplatin+Pyridostigmine (Cis+Pyr). We induced gastrointestinal dysmotility by administering 3 mg kg-1 of cisplatin once week for 5 weeks. The Ex was swimming (1 h per day/5 days per week for 5 weeks with 5% b.w.). GE was evaluated through the colorimetric method of fractional red phenol recovery 10 min after feeding. Pyr groups received 1.5 mg kg-1, p.o. or concomitant Cis treatment. Moreover, gastric contraction in vitro and hemodynamic parameters such as MAP, HR, and evoked baroreflex sensitivity were assessed, as well as sympathetic and parasympathetic tone and intrinsic heart rate (IHR). Cis decrease GE vs. saline (p<0.05). Cis+Ex or Cis+Pyr prevented (p<0.05) decrease in GE vs. Cis rats. Cis decreased (p<0.05) gastric responsiveness in vitro vs. saline. Cis+Ex or Cis+Pyr prevented this phenomenon. Cis treatment increase MAP and decrease in HR (p<0.05) vs saline. Cis+Ex or Cis+Pyr attenuated (p<0.05) both alterations. Cis increased sympathetic tone and decreased vagal tone and IHR (p<0.05) vs. the saline. Cis+Ex or Cis+Pyr prevented those effects vs. the Cis group. In conclusion, physical exercise and pyridostigmine treatment improves autonomic dysfunction and prevented GE delay and changes in hemodynamic parameters, baroreflex sensitivity, and cardiac autonomic control in cisplatin-treated rats.

Antidiarrheal activity of α-terpineol in mice.

Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α -Terpineol (α-TPN) in different diarrhea models in rodents. The antidiarrheal effect of α-TPN in the treatment of acute diarrhea and enteropooling induced by castor oil or PGE2 in Swiss mice pretreated orally with saline (NaCl 0.9%), Loperamide (5 mg/kg) and α-TPN (6.25, 12.5, 25 and 50 mg/kg) was analyzed. Additionally, parameters of severity, total weight of faeces and post-treatment for 4 h were evaluated. Modulation of the opioid and cholinergic pathways was performed and intestinal transit model using activated charcoal as marker was also used. The effect of α-TPN on secretory diarrhea was investigated using the model of fluid secretion in intestinal loops isolated from cholera toxin-treated mice. α-TPN showed antidiarrheal effect (*p < 0.05), reducing the total stool amount (*55%, *48%, *44%, *24%) and diarrheal (*47%, *66%; *56%, 10%) respectively for the doses tested. All doses investigated in the enteropooling test presented significant changes (*46%, *78%, *66%, *41% respectively) in relation to the control. α-TPN through the muscarinic pathway reduced the gastrointestinal transit (*31%), besides inhibiting PGE2-induced diarrhea (*39%). α-TPN also reduced fluid formation and loss of Cl- ions, by interacting directly with GM1 receptors and cholera toxin, thus increasing the uptake of intestinal fluids. The results suggest an anti-diarrheal activity of α-TPN due to its anticholinergic action, ability to block PGE2 and GM1 receptors and interaction with cholera toxin in secretory diarrhea, making it a promising candidate drug for the treatment of diarrheal diseases.

Moderate-intensity exercise and renin angiotensin system blockade improve the renovascular hypertension (2K1C)-induced gastric dysmotility in rats.

Actually, arterial hypertension is a major public health concern, which involves the renin angiotensin aldosterone system (RAS), via activation of the angiotensin receptors AT1 and AT2 of the cardiovascular system. Although angiotensin is an important stimulant of the gut permeability to sodium and water, little is known about the effects of arterial hypertension on gut motor behavior. Thus, we evaluated in rats the effect of hypertension induced by two-kidney one-clip (2K1C) model on the gastric motility, as well as the influence of exercise and RAS blockers treatment in such phenomenon. One week after surgery the rats were treated with Aliskiren (50 mg·kg-1, p.o.), Captopril (50 mg·kg-1, p.o.) or Losartan (10 mg·kg-1, p.o). Other group of rats was submitted to swimming with 5% body weight overload. After 4 weeks of physical training or pharmacological treatment, we assessed the gastric retention in all groups (GR) of a liquid test meal, the mean arterial pressure (MAP), the heart rate (HR) and the HR variation (HRV) as well as the in vitro contractility of gastric fundus. Renovascular hypertension increased (p < 0.05) the GR, MAP and HR, a phenomenon prevented by pretreatment with RAS blockers or exercise. The two kidney one-clip Hypertension (2K1C) decreased (p < 0.05) the gastric fundus responsiveness, a phenomenon also prevented by exercise. It conclusion, renovascular hypertension delays the gastric emptying of liquids, a phenomenon involving the activation of RAS, where exercise or blockade with aliskiren, captopril and losartan prevent gastric dysmotility.