Investigação dos efeitos centrais e gastroprotetores do isopulegol em camundongos

Abstract

Isopulegol is a monoterpene alcohol present in the essential oils of various plants, and has been used in the manufacture of fragrances with blossom compositions. In order to investigate its effects on animal models of CNS actions, isopulegol was administered to male Swiss mice at single doses of 25 and 50 mg/kg 30 (i.p.) or 60 min (p.o.) before the experiments. Control animals received vehicle (saline 0.9% in 0.3% Tween). For investigating the involvement of GABAA/BZP system, flumazenil was utilized 15 min before the treatments. Monoamines and their metabolites concentration were also investigated in striatum of mice after acute administration of isopulegol. The results in EMP and hole board tests suggest possible anxiolytic-like effects from isopulegol, which were reversed by flumazenil pretreatment, indicating probable positive modulation of benzodiazepine-sensitive GABAA receptors. The anxiolytic-like effects were not accompanied by sedation, as reduced locomotion was not observed in open field test. Parameters observed in the forced swimming, tail suspension and pentobarbital sleeping time tests support the idea that isopulegol possibly presents depressant activity on the CNS. The observed central effects were corroborated by DA and NE decreased levels (without changes in 5-HT levels). In order to verify whether isopulegol would be able to exert any protector effect in PTZ-induced convulsions, mice received isopulegol (25, 50, 100 and 200 mg/kg, i.p. or p.o.) or vehicle before PTZ (99 mg/kg, s.c.). The involvement of GABAA/BZP receptors was also investigated by flumazenil pretreatment. Also, it was evaluated whether antioxidant properties from isopulegol would be related to its possible anticonvulsant effect. Results showed that isopulegol (100 and 200 mg/kg) presented anticonvulsant and bioprotective effects against PTZ-induced convulsions. At 100 and 200 mg/kg doses, isopulegol induced marked sedative effect (decreased locomotion in open field test). Flumazenil pretreatment decreased the prolongation of convulsion latency induced by isopulegol, suggesting a possible involvement of direct activation of benzodiazepine site of GABAA. Isopulegol also significantly prevented PTZinduced increase in lipid peroxidation, preserved catalase activity in normal levels, and prevented the PTZ-induced loss of GSH in hippocampus of mice. In order to investigate whether isopulegol would be able to promote gastroprotective effects in ethanol- and indomethacin-induced gastric ulcer models, mice received isopulegol (25, 50, 100 and 200 mg/kg, p.o.) before ethanol (0.2 mL, p.o.) or indomethacin (20 mg/kg, p.o.). A histopathological assessment of stomachs was conducted, as well as possible mechanisms involved in gastroprotective action were also investigated. Isopulegol presented significant gastroprotective effect in both ethanol- and indomethacin-induced ulcer models. This effect was corroborated by the histopathological assay, which showed that pretreatment with isopulegol was able to inhibit the ethanol-induced microscopically alterations. The pretreatment with indomethacin and glibenclamide was able to reverse the gastroprotection induced by isopulegol. The PTZ-induced loss of GSH in stomachs and liver was also preserved by pretreatment with isopulegol. These results suggest that the gastroprotective effects induced by isopulegol appear to be mediated, at least in part, by endogenous prostaglandins, K+ATP channel opening and antioxidant proprieties related to GSH increased.