Effect of subchronic administration of agomelatine on brain energy metabolism and oxidative stress parameters in rats

Abstract

Aims:The aim of this study was to investigate the effect of subchronic administration of agomelatine on energy metabolism, oxidative stress markers and antioxidant defense in the brains of rats. Methods:The animals received daily intraperitoneal injections of agomelatine (10, 30 or 50 mg/kg) or saline for 14 days. The prefrontal cortex, cerebellum, hippocampus, striatum and posterior cortex were analyzed. Results:The findings showed that complex I was activated in the prefrontal cortex, cerebellum and striatum and inhibited in the posterior cortex at the 10-mg/kg dose, and inhibited in all brain areas analyzed at the 30-mg/kg and 50-mg/kg doses. Complex II was activated in the posterior cortex at the 50-mg/kg dose. Complex IV was inhibited in the striatum and posterior cortex at the 10-mg/kg dose, inhibited in the striatum at the 30-mg/kg dose and activated in the hippocampus at the 50-mg/kg dose.Creatine kinase activity was inhibited in the striatum at the 10-mg/kg and 30-mg/kg doses. Lipid peroxidation and protein carbonylation levels were not changed after the administration of agomelatine. Superoxide dismutase activity was increased in the striatum at the 10-mg/kg dose, and catalase activity was inhibited in the cerebellum at the 10-mg/kg dose and increased in the posterior cortex at the 30-mg/kg dose. Conclusions:Our results are consistent with other studies showing that some antidepressants may influence brain energy metabolism and oxidative stress parameters and expand knowledge about the effects of agomelatine in biochemical parameters in the brains of rats.

Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin‐induced diabetes in mice

“…Our results regarding the beneficial effects of agomelatine on the antioxidant capacity are consistent with other studies showing that some antidepressants including agomelatine have antioxidant properties [49][50][51]. Agomelatine administration has been reported to cause increases in the activities of superoxide dismutase (SOD) and of catalase (CAT) in the posterior cortex and striatum in rats [52]. Therefore, given that antioxidants can protect against neuronal damage caused by oxidative stress, the increase in total antioxidant capacity after agomelatine administration may responsible for its beneficial effect in the prevention of diabetes.…”

Genome-wide analysis of LPS-induced inflammatory response in the rat ventral hippocampus: Modulatory activity of the antidepressant agomelatine

“…Other transcripts, belong to pathways related to the synthesis, generation and production of reactive oxygen species, suggesting an anti-oxidant effect of the antidepressant that may be associated with its structural analogy with melatonin, a well-known antioxidant agent (Reiter et al 2008). By regulating these pathways, agomelatine could counteract the oxidative stress associated to the inflammatory response, an effect in line with its ability to positively modulate energy metabolism and oxidative stress parameters (de Mello et al 2015).…”

The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine

“…In this study, we also found an increased expression of Cat in the hypothalamus and reduced methylation status of the Cat promoter region in the cerebral cortex in the agomelatine-treated CMS rats. Mello et al (2016) demonstrated that agomelatine increased Sod activity in the striatum, whereas Cat activity was reduced in the cerebellum and elevated in the posterior cortex [ 58 ]. Thus, the results suggest that agomelatine may modulate the expression and promoter methylation of gene-encoding Cat.…”