Molecular mechanisms of behavioral manifestations of neurotoxicity induced by platinum-based chemotherapeutics: a beneficial role for antioxidant supplementation

Abstract

Summary. For decades, platinum-based chemotherapeutics have been widely used in clinical protocols for numerous malignancies. However, despite their undisputed therapeutic potential, there clinical usage is limited by serious adverse effects. Neurotoxicity is one of the most frequent side effects of platinum-based compounds, and is associated with oxidative damage and pro-apoptotic activity. Thus, antioxidant supplementation may play a potential role in the treatment of platinum-based drug-induced neurotoxicity. In support of this, encouraging results were achieved using a variety of antioxidant-rich compounds. Our results suggest that synthetic and natural products with high antioxidant content may attenuate cisplatin-induced neurotoxicity by preventing oxidative damage and apoptosis in the brain. The beneficial role of antioxidant supplementation is further supported by their observed ability to reverse cisplatin-induced behavioral deterioration.