Role of lycopene in mitochondrial protection during differential levels of oxidative stress in primary cortical neurons

Abstract Reactive oxygen species (ROS) are a major contributor to intracellular organelle damage in neurons. ROS-induced mitochondrial dysfunction is highly associated with impaired energy metabolism that occurs during neurodegeneration. Therefore, the use of antioxidants may be beneficial in protecting the brain from injury caused by ROS. Lycopene is a carotenoid that exhibits neuroprotective properties via its antioxidant capacity. In this study, we hypothesize that treatment with lycopene attenuates hydrogen peroxide-induced oxidative stress in primary cortical neurons. We further tested if lycopene reverses mitochondrial dysfunction caused by ROS. Primary rat cortical neurons were treated with lycopene, hydrogen peroxide, or a combination of both. We used two different concentrations of hydrogen peroxide (25 and 100 μM) to examine a moderate or a high ROS challenge. Treatment with hydrogen peroxide significantly increased intracellular ROS, decreased mitochondrial membrane potential, and depleted neuronal ATP. When neurons were co-treated with lycopene and 25 μM hydrogen peroxide, lycopene attenuated hydrogen peroxide-mediated mitochondrial dysfunction. Interestingly, neuroprotective properties of lycopene were only found during exposure to 25 μM hydrogen peroxide, but not in a 100 μM treated group. We further found that lycopene prevents accumulation of the cleaved form of B-cell lymphoma-extra large, ΔN-Bcl-xL. Since ΔN-Bcl-xL causes loss of mitochondrial inner membrane potential which impairs energy metabolism and leads to neuronal death, prevention of ΔN-Bcl-xL accumulation may be an important mechanism explaining lycopene-mediated neuroprotection. Our study suggests that mitochondria are a key target during lycopene-mediated neuroprotection but that the efficacy of lycopene as a neuroprotectant may vary under different levels of ROS.