α-tocopherol alleviates ketamine toxicity in rat brain neurons.
Enayatollah Seydi, Sana Ghanizadeh, Farzaneh Jokar, Farzaneh Kamranfar, Jalal Pourahmad
BMC Pharmacology and Toxicology January 30, 2026 DOI: 10.1186/s40360-026-01083-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Rat brain neurons |
| Interventions | Ketamine α-Tocopherol |
| Dose | Ketamine 2, 4, 8 µM; α-Tocopherol 10 µM |
| Measures | cell viability, ROS levels, mitochondrial and lysosomal membrane damage, cytochrome c release |
| Topics | Ketamine Esketamine |
| Keywords | Cytotoxicity Lysosome Mitochondria Neurotoxicity Oxidative stress Α-tocopherol |
| Key points | Α-tocopherol at 10 µM prevented ketamine-induced oxidative stress, membrane damage, and apoptosis signaling in rat brain neurons. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 3
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
- Ketamine-induced neurotoxicity is mediated through endoplasmic reticulum stress in vitro in STHdhQ7/Q7 cells. Neurotoxicology July 2022
- Neuroprotective effect of hesperidin and its combination with coenzyme Q10 on an animal model of ketamine-induced psychosis: behavioral changes, mitochondrial dysfunctions, and oxidative stress Future Journal of Pharmaceutical Sciences January 15, 2022