Efeitos da naringenina em modelos animais de convulsão e depressão: aspectos comportamentais, envolvimento do adrenorreceptor alfa-1 e estresse oxidativo

Abstract

Epilepsy has a high prevalence and severity in the world. Beyond the severity of the epileptic disorder per se, this disorder is usually accompanied by psychiatric comorbidities, and depression is the most prevalent. Thus, the treatment of epilepsy should not be restricted only to seizures, but should also include the treatment of depression, since both conditions directly affect the quality of life of patients. Accordingly, the effects of naringenin in classical models of anxiety, depression and seizure were studied. In this work, we investigated the involvement of the α1-adrenoceptor in the effects of naringenin in the models aforementioned, as well as the effects of naringenin treatment on oxidative stress by means of lipid peroxidation and concentration of nitrite/nitrate in brain areas. Naringenin was administered in mice, in acute and chronic (15 days) forms, at doses of 10, 20 and 50 mg / kg (p.o.) to perform the open field test, elevated plus maze (EPM), tail suspension and pilocarpine-induced seizure. Results showed that the acute and chronic treatments with naringenin did not affect the number of crossings, rearing and grooming of the animals. They also did not show anxiolytic effect on the EPM test but showed anti-immobility effect in the tail suspension test at all doses of the acute treatment, and in doses of 10 and 20 mg / kg in the chronic treatment. In the test of seizure induced by pilocarpine, acute treatment with three doses of naringenin did not affect the latency of seizure onset nor death of animals, however chronic treatment with naringenin at doses of 20 and 50 mg / kg reduced the seizure latency, reducing also, death latency in the treatment at the highest dose (50 mg / kg). Research on engagement of the α1-adrenoceptor showed that this receptor seems to mediate the antidepressant effects of acute and chronic treatments with naringenin at a dose of 20 mg / kg. Likewise, it appears to be responsible for the reduction of the seizure onset latency observed in acute and chronic naringenin treatments in doses of 20 and 50 mg / kg, also reducing latency of death observed in chronic treatment at the highest dose. The evaluation of oxidative stress showed that acute treatment with three doses of naringenin had no effect on this parameter. However, chronic treatment with naringenin at a dose of 10 mg / kg reversed the increased levels of lipid peroxidation, without interfering with the concentration of nitrite/nitrate in brain areas. Chronic treatment at a dose of 20 mg / kg did not interfere with peroxidation lipid concentration nor nitrite/nitrate and chronic treatment in the highest dose (50 mg / kg) increased the levels of lipid peroxidation in the hippocampus, without interfering with other brain areas and in the concentration of nitrite/nitrate. In conclusion, this study suggests that the dose of 10 mg / kg proved to be the safest in relation to the treatment of comorbid depression in epilepsy, and that the effects of naringenin on the antidepressant activity and on the latency of seizure and death appears to be mediated by α1-adrenoceptor.