Efeito neuroprotetor do ácido gálico em modelos experimentais de mania e neuroinflamação

Abstract

Bipolar affective disorder (BD) is a chronic psychiatric illness that presents episodes of depression and mania. Neurochemical, inflammatory and oxidative stress changes have been reported in patients with this psychiatric disorder as well as in experimental models. Gallic acid is a polyphenol found in several natural products and has important pharmacological properties such as antioxidant, anti-inflammatory and neuroprotective actions. The aim of this thesis was to review the literature on the advances in the therapeutic potential of natural compounds and derivatives against TAB, as well as to evaluate the neuroprotective effect of gallic acid in two experimental models that mimic pathological mechanisms associated with TAB. For the ketamine-induced mania protocol, adult male rats were used, which were divided into seven groups: I (saline); II (gallic acid 50 mg / kg), III (gallic acid 100 mg / kg), IV (ketamine), V (ketamine + gallic acid 50 mg / kg) VI (ketamine + gallic acid 100 mg / kg) and VII ( ketamine + lithium 45 mg / kg). For 14 days, the animals received saline, gallic acid or lithium orally. Between days 8 and 14 the animals also received ketamine (25 mg / kg, i.p.) or saline. For the lipopolysaccharide-induced neuroinflammation protocol (LPS), male mice were used, which were divided into four groups: I (saline); II (LPS), III (LPS + gallic acid 50 mg / kg), IV (LPS + gallic acid 100 mg / kg). The animals received oral water or gallic acid for 14 days. Between the 8th and the 14th day the animals also received saline or LPS (250 μg / kg) via intraperitoneal. In both protocols, behavioral tests were carried out at the end of the treatment to assess locomotion and memory and after the animals were euthanized and the cerebral cortex, hippocampus and striatum were collected for biochemical analyzes. First, the review manuscript demonstrated that both preclinical and clinical studies confirmed the potential of compounds such as omega-3, inositol, N- acetylcysteine, blackberry extracts, blueberry and Cecropia pachystachya, quercetin, alpha-lipoic acid and carbon in prevention in managing the phases of BD. In addition, the results of this thesis also demonstrated that gallic acid was able to prevent hyperlocomotion, oxidative damage and changes in ketamine-induced acetylcholinesterase activity in the brain structures of rats. LPS induced impairment in the memory of mice and caused oxidative damage in the cortex, hippocampus and striatum, which can be evidenced by the increase in reactive oxygen species, lipid peroxidation and nitrites, as well as decreased antioxidant defenses. Treatment with gallic acid has been shown to be effective in reversing memory deficits and protecting brain regions from oxidative stress induced by LPS. Thus, the findings of the present study demonstrate that gallic acid, a natural product, can be considered a promising therapy for BD.