Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures

Abstract

Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models.

Fig. 1

Determination of lipid peroxidation, nitrite content, and catalase activity in the PFC, HC, and ST of female Swiss mice after strychnine-induced seizure. Animals were submitted to a 30-min observation and afterwards sacrificed. Each bar represents mean ± S.E.M. of 6–8 animals/group. a, b, c, and d : P < 0.05 when compared to controls, agomelatine 25, 50, or 75 mg/kg, respectively (ANOVA and Tukey test post hoc)

Fig. 2

Determination of lipid peroxidation, nitrite content, and catalase activity in the PFC, HC, and ST of female Swiss mice after pilocarpine-induced seizure. Animals were submitted to a 30-min observation and afterwards sacrificed. Each bar represents mean ± S.E.M. of 6–8 animals/group. a and b: P < 0.05 when compared to controls and agomelatine 25 mg/kg, respectively (ANOVA and Tukey test post hoc)

Fig. 3

Determination of lipid peroxidation, nitrite content, and catalase activity in the PFC, HC, and ST of female Swiss mice after PTX-induced seizure. Animals were submitted to a 30-min observation and afterwards sacrificed. Each bar represents mean ± S.E.M. of 6–8 animals/group. b: P < 0.05 when compared to agomelatine 25 mg/kg (ANOVA and Tukey test post hoc)

Fig. 4

Determination of the lipid peroxidation, nitrite content, and catalase activity in the PFC, HC, and ST of female Swiss mice after PTZ-induced seizure. Animals were submitted to a 30-min observation and afterwards sacrificed. Each bar represents mean ± S.E.M. of 6–8 animals/group