General anesthesia induced by ketamine or sevoflurane disrupts iron metabolism, causing iron overload in hippocampal neurons and brain tissue. This iron overload triggers ferroptosis, a form of iron-dependent cell death, leading to cognitive deficits in young rats and aged mice. The iron chelator deferiprone reduces mitochondrial dysfunction, ferroptosis, and cognitive impairment. The mechanism involves NMDAR-RASD1 signaling activating DMT1, which mediates iron uptake. Disturbed iron metabolism may contribute to anesthesia-related neurotoxicity and cognitive decline.
Propofol and ketamine increase the activity of certain potassium channels (TASK-3 and SK3, respectively), while pentobarbital and ketamine decrease the activity of SK1 channels. These effects were observed in Xenopus oocytes expressing seven types of potassium channels. Molecular docking simulations identified specific amino acid residues where each anesthetic binds: propofol to Q126 of TASK-3, ketamine to S290 of SK1 and S467 of SK3, and pentobarbital to S330 and T358 of SK1. Because these potassium channels help regulate respiration, heart rhythm, and blood vessel dilation, the findings suggest a molecular basis for the cardiovascular and respiratory side effects of intravenous general anesthetics.