It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.
Fluoride (F) is an element with proven prooxidative properties and an ability to cross the BBB. It can induce neuroinflammation and neurodegeneration which may be clinically manifested as memory, concentration or cognitive disorders [
28,
29]. The most important toxic effects of F in the brain include increase in prooxidative processes rate with subsequent damage to neurons, impairment of signal transmission within synapses, and induction of inflammation [
30]. Mentioned ravages concerning fluoride action may possibly be in relation to nervous tissue degenerative changes reported in AD [
31].
Fluoride exerts the inhibitory influence on various enzymes’ expressions and activities. Cholinesterases belong to the enzymes with their activities being inhibited after fluoride exposure [
32]. The arresting effect of fluoride compounds has been reported for at least for tens of years. In 1985, Baselt et al. reported decreased cholinesterase activity in postmortem, fluoride preserved blood samples in comparison to the postmortem blood samples with no fluoride preservation [
33]. Currently many studies are focused on the methane sulfonyl fluoride (MSF) examination, because of its acetylcholinesterase inhibitory properties in the irreversible manner [
34]. MSF attaches the enzyme (AChE) catalytic site solidly, entirely irreversibly [
34] and without any possibility of spontaneous hydrolysis of the covalent MSF-ACh bond [
35] MSF exerts the selective inhibitory properties on brain AChE [
36].
