Chemical agents protective against rotenone-induced neurotoxicity

Abstract Rotenone is a broadly used organic pesticide with neurotoxicity as a serious side effect for non-target organisms. The inhibition of mitochondrial complex I is the principal mechanism of rotenone toxicity that leads to oxidative stress, apoptosis, and decreased autophagy. Several chemical compounds have been demonstrated to exhibit antioxidant, antiapoptotic, and autophagy enhancement in both in vitro and in vivo studies. Some chemical agents can ameliorate rotenone-induced neurotoxicity through their antioxidant, anti-inflammatory, and anti-apoptotic properties. They also inhibit the accumulation of α-synuclein, control dopamine release, affect ion channels, and induce autophagy. Clinical trials are essential to reinforce the effectiveness of any chemical in managing patients with rotenone neurotoxicity.