RESUMO
Fat burners are a category of nutritional supplements that are claimed to increase the metabolism and promote greater energy expenditure, leading to weight loss. However, little is known about the side effects on gastrointestinal motility. In this study, we evaluated the effect of ingestion with a fat burner named Thermbuterol® (THERM) on the gastric motility and food behavior of mice. THERM compounds were identified using nuclear magnetic resonance (NMR). Mice received variable doses of THERM (10, 50, 100 or 300 âmg/kg, p.o.) or NaCl 0.15 âM (control). Gastric emptying (GE) was assessed using the phenol red technique. Another set of mice was pretreated with intraperitoneal administration of hexamethonium (HEXA, 10 âmg/kg), prazosin (PRAZ, 0.25 âmg/kg), propranolol (PROP, 2 âmg/kg), parachlorophenylalanine (PCPA, 300 âmg/kg) or ondansetron (ONDA, 50 âµg/kg) 30 âmin before THERM treatment for evaluation of GE. We assessed the gastrointestinal responsiveness in vitro as well as THERM's effects on food behavior. Caffeine was the major compound of THERM, identified by NMR. THERM 100 and 300 âmg/kg decreased GE compared to the respective controls. Pretreatment with PRAZ or PROP did not prevent gastric dysmotility induced by THERM 100 âmg/kg. However, the pretreatment with HEXA, ONDA or PCPA prevented GE delay induced by THERM. In vitro, THERM relaxed contractions in strips of longitudinal gastric fundus and duodenum. THERM also increased food intake, which was prevented by PCPA and ONDA treatments. THERM decreased GE of a liquid and increased food intake in mice, a phenomenon mediated by the autonomic nicotinic receptors and serotoninergic receptor.
RESUMO
Phosphodiesterase type-5 (PDE5) specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. The PDE5 inhibitor sildenafil is a well-known vasodilator that also has gastrointestinal myorelaxant properties. In the present study, we further investigated sildenafil-induced myorelaxation in rat isolated duodenum, assessing its interaction with nitric oxide (NO) synthase and K(+) channel opening. The spontaneous contractions of duodenal strips were reversibly inhibited by sildenafil (0.1-300 microM) in a concentration-dependent manner [mean (95% confidence interval); EC(50) = 6.8 (2.7-17.3) microM]. The sildenafil-induced myorelaxation was significantly decreased by the NO synthase inhibitor N-nitro-L-arginine methyl ester [increasing the EC(50) value to 41.9 (26.1-67.3) microM]. Sodium nitroprusside or forskolin pretreatments enhanced the sildenafil-induced myorelaxation. In isolated strips pretreated with BaCl(2) (0.2 mM), 4-aminopyridine (4-AP, 3 mM), or glybenclamide (1 microM), the sildenafil-induced EC(50) value was significantly increased to 32.8 (19.1-56.4), 27.1 (15.2-48.3) and 20.1 (16.4-24.7) microM, respectively. Minoxidil (50 microM) or diazoxide (100 microM) also significantly attenuated the sildenafil-induced potency. In conclusion, the NO synthase/cyclic nucleotide pathway activation is involved in sildenafil-induced inhibition of spontaneous duodenal contractions. Its pharmacological action seems to be influenced by K(+) channel opening, especially the voltage-sensitive ones, being inhibited by 4-AP and K(ATP) channels, sensitive to glybenclamide.