Análise bioquímica do efeito neuroprotetor da N-acetilcisteína em peixes-zebra

Abstract

The idea that stress is a major factor in the onset of mental disorders, such as anxiety, is widely accepted. Chronic stress is a potent inducer of oxidative damage in the central nervous system, with lipid peroxidation representing one of the most deleterious biological markers of this condition. This study investigated the protective effect of N-acetylcysteine (NAC) on the integrity of brain lipid membranes in zebrafish subjected to chronic unpredictable stress (CUS) for 7 days. Animals were exposed to the CUS protocol for 7 days using the following stressors applied on alternating days and at varying times: net chasing, water heating or cooling, crowding, three consecutive tank changes, and dorsal body exposure. On day 7, in addition to stress exposure, fish were either treated or not treated by immersion in N-acetylcysteine (NAC), fluoxetine (FLU), or ketamine (KET) for 20 minutes. Twenty-four hours after treatment, the animals were anesthetized and euthanized by rapid cooling, and the brain tissue was collected, processed, and stored for biochemical analysis. Oxidative damage was quantified by measuring thiobarbituric acid reactive substances (TBARS) levels. Our results demonstrated that CUS induced a robust, significant increase in TBARS levels, indicating severe degradation of brain membrane lipids. Treatment with NAC, FLU, or KET did not induce lipid damage in non-stressed animals; however, FLU and KET treatments were unable to reverse lipid peroxidation in stressed animals. In contrast, NAC treatment sustainably reversed the lipid damage caused by CUS. These findings demonstrate that NAC may exert sustained effects following a single pharmacological exposure, acting as a neuroprotective agent in stress-related mental disorders by specifically preventing lipid peroxidation resulting from prolonged stress.