A review of mechanisms underlying the protective effects of natural compounds against arsenic-induced neurotoxicity.

Arsenic (As) is a toxic metalloid that is widely distributed in the earth's crust. People are continuously exposed to this toxicant in their food and drinking water. Inorganic arsenic occurs in two oxidation states, arsenite 3+ (iAs3+) and arsenate 5+ (iAs5+). The most toxic form is its trivalent form which interferes with the electron transfer cycle and induces overproduction of reactive oxygen species, leading to depletion of the antioxidant defense system, as well as altering fatty acid levels and mitochondrial action. Since arsenic crosses the blood-brain barrier, it can damage cells in different regions of the brain, causing neurological disorders through the induction of oxidative stress, inflammation, DNA damage, and cell death. Hydroxytyrosol, taurine, alpha-lipoic acid, ellagic acid, and thymoquinone have been shown to effectively alleviate arsenic-induced neurotoxicity. The protective effects are the result of the anti-oxidative and anti-inflammatory properties of the phytochemicals and in particular their anti-apoptotic function via the Nrf2 and PI3/Akt/SIRT1 signaling pathways.