α-tocopherol alleviates ketamine toxicity in rat brain neurons.

Ketamine, a drug with various pharmacological effects, can cause brain side effects and neurotoxicity by inducing oxidative stress and impairing mitochondrial function. In rat brain neurons, ketamine reduced cell viability (half-maximal inhibitory concentration of 4 µM) and, at 2, 4, and 8 µM, increased reactive oxygen species, damaged mitochondrial and lysosomal membranes, and raised cytochrome c release. The antioxidant α-tocopherol at 10 µM prevented these effects caused by 8 µM ketamine: it reduced oxidative stress, preserved membrane integrity, and decreased apoptosis signaling, suggesting a potential protective role against ketamine neurotoxicity.

Study at a glance

Abstract

Ketamine exhibits various pharmacological effects due to its high efficacy, but reports also indicate its potential to cause brain side effects and neurotoxicity. It can induce oxidative stress and impair mitochondrial function, although the exact mechanism of its neurotoxicity remains unclear. In this study, we examined the effects of α-tocopherol on ketamine-induced toxicity in rat brain neurons. We measured cell viability, ROS levels, membrane damage in mitochondria and lysosomes, and cytochrome c release from mitochondria. Results showed that ketamine significantly reduced neuron viability, with an IC50 of 4 µM. At concentrations of 2, 4, and 8 µM, ketamine increased ROS production, damaged mitochondrial and lysosomal membranes, and raised cytochrome c release. Notably, α-tocopherol at 10 µM prevented these effects caused by 8 µM ketamine. It reduced oxidative stress, preserved membrane integrity, and decreased apoptosis signaling, suggesting its potential antioxidant role in counteracting ketamine neurotoxicity.