ABSTRACT: Nerve growth factor differentiated PC12 cells were used to examine the antioxidative and anti-inflammatory effects of astaxanthin (AX) and canthaxanthin (CX). PC12 cells were pretreated with AX or CX at 10 or 20 μM, and followed by exposure of hydrogen peroxide (H2O2) or 1-methyl-4-phenylpyridinium ion (MPP+) to induce cell injury. H2O2 or MPP+ treatment significantly decreased cell viability, increased lactate dehydrogenase (LDH) release, enhanced DNA fragmentation, and lowered mitochondrial membrane potential (MMP) (P < 0.05). The pretreatments from AX or CX concentration-dependently alleviated H2O2 or MPP+-induced cell death, LDH release, DNA fragmentation, and MMP reduction (P < 0.05). Either H2O2 or MPP+ treatment significantly increased malonyldialdehyde (MDA) and reactive oxygen species (ROS) formations, decreased glutathione content, and lowered glutathione peroxidase (GPX) and catalase activities (P < 0.05). The pretreatments from AX or CX significantly retained GPX and catalase activities, and decreased MDA and ROS formations (P < 0.05). H2O2 or MPP+ treatment significantly decreased Na+-K+-ATPase activity, elevated caspase-3 activity and levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α (P < 0.05); and the pretreatments from these agents significantly restored Na+-K+-ATPase activity, suppressed caspase-3 activity and release of IL-1, IL-6, and TNF-α (P < 0.05). Based on the observed antioxidative and anti-inflammatory protection from AX and CX, these 2 compounds were potent agents against neurodegenerative disorder.