Investigation of oxidative stress and DNA damage caused by atomoxetine in rats

Attention Deficit and Hyperactivity Disorder (ADHD) is a neurological-based disorder that is often seen in childhood but can continue into adulthood, manifested by inattention and/or hyperactivity, uncontrolled response, or sudden and impulsive reactions. Stimulant drugs are generally preferred for symptomatic treatment the use of atomoxetine, a non-stimulant drug. Due to the side effects and addiction potential of stimulant drugs has come to the fore in recent years. Atomoxetine inhibits norepinephrine transporters in the presynaptic space in the prefrontal cortex of the brain, thereby increasing norepinephrine levels in particular. However, besides its therapeutic potential, it causes a change in the amount of neurotransmitter. Therefore, it has been predicted that it can change the level of oxidative stress. In this thesis, changes in brain tissue were investigated after the combined administration of low/high dose Atomoxetine and vitamin E in healthy rats without animal modeling. According to the findings obtained, Vit E was showed a positive effect by significantly reducing the oxidative stress level and increasing the antioxidant level in the applications performed together and separately. It was observed that atomoxetine applications caused an increase in DNA damage, with the addition of Vit E application DNA damage was reduced significantly. In addition, when the histopathological changes and immunochemical markers in the brain are evaluated; It has been observed that Atomoxetine administration causes pathological changes in the brain and increases the accumulation of hyperphosphorylated Tau and IL-6. As a result, in our study it was observed that Atomoxetine administration increased the oxidative stress level in the brain tissue, causing new histopathological formations and immunochemical changes, while the addition of vitamin E provided positive effects on the relevant parameters.