Interação entre o brometo de piridostigmina e o desbalanço superóxido-peróxido de hidrogênio na cito-genotoxicidade de células neurais e imunes mononucleares ; Interaction between pyridestigmine bromide and hydrogen superoxide-peroxidal debalance in cyto-genotoxicity of neural and immune mononuclear cells

Pyridostigmine bromide (PB) is a reversible acetylcholinesterase inhibitor (AChE), and the first line of symptoms associated with neuromuscular junction disorders (JNM) and has been used prophylactically in the Persian Gulf War (GWI), for prevention of post-traumatic stress, exposure to heat and pesticides. The role of PB in relation to GWI disease, which includes symptoms such as fatigue, cognitive and musculoskeletal dysfunction, is still controversial. Since it is used alone it does not appear to present intense toxic effects, however associated to other drugs and chemical agents it becomes genotoxic and inducer of apoptosis in animals. Therefore, the objective of this study was to evaluate the interaction between PB and superoxide-hydrogen peroxide (S-HP) imbalance in the cytogenotoxicity of neural and mononuclear immune cells. Three experimental designs were conducted. The first study aimed to evaluate the effect of CP on cytotoxicity and genotoxicity in SHSY-5Y neural cells. An in vitro investigation using human neural cells (SHSY-5Y) was performed. Cells were exposed to PB in different concentrations, based on the plasma drug concentration for the treatment of Myasthenia Gravis MG (40 ng / mL). The concentration curve of the drug showed an inhibition of AChE activity. However, this effect was transient and did not involve the regulation of AChE gene expression. In general, PB did not trigger oxidative stress except at the highest concentration (80 ng/mL), protein damage and DNA damage were detected. Genotoxic effects were confirmed by increased expression of p53 and DNA methyltransferase 1 (DNMT1) genes, which are associated with cellular DNA repair. The concentration of 40 ng/mL, which is the minimal therapeutic dose, showed a less intense cytotoxic effect, promoting a greater cell proliferation and mitochondrial activity compared to the untreated group. These effects were corroborated by increased telomerase gene expression. Two other protocols were conducted to evaluate the genetic influence associated ...