Investigação do papel preventivo do ácido tânico frente ao modelo de Transtorno Depressivo Maior induzido por lipopolissacarídeo em camundongos

Abstract

Major Depressive Disorder (MDD) is a very common multifactorial neuropsychiatric disorder that currently affects around 350 million people worldwide. There are different hypotheses about the pathophysiology of this disorder, one of them being about oxidative stress. It is known that deregulated redox signaling is crucial in the pathophysiology and neuroprogression of this disease. Tannic acid (TA) is a polyphenol produced by the secondary metabolism of plants and is part of the group of hydrolysable tannins. Tannins are phenolic substances that present several pharmacological activities, among them antimutagenic, anticarcinogenic and antioxidant activities. Considering the above, the objective of this project was to evaluate the antidepressant and antioxidant effect of AT in an animal model of lipopolysaccharide (LPS)-induced depression. For this, mice received water or TA (30 mg/kg or 60 mg/kg) intragastric route for 7 days, with the administration of LPS (830 μg/kg) on the last day of treatment. After 24 hours, the animals were submitted to forced swimming (TNF), open field (OFT), tail suspension (TST) and splash tests (ST), and euthanasia for removal of the brain structures and subsequent evaluation of biochemical parameters. The endotoxin induced depressive-like behavior in these mice and this was attenuated by TA pretreatment. In the cerebral cortex, hippocampus, and striatum, LPS increased lipid peroxidation and reactive oxygen species production, and this was also prevented by TA administration. TA treatment also prevented a decrease in catalase activity within the striatum. Further, LPS administration caused increased levels of TNF-α in all brain structures, and this was prevented in the cortex by TA treatment. In conclusion, TA shows many neuroprotective properties, with demonstrated antioxidant, anti-inflammatory and antidepressant effects in this animal model of MDD. Therefore, this compound could provide an alternative therapeutic approach for the treatment and/or prevention of this pathology.