title: Carnosine protects against the neurotoxic effects of a serotonin-derived melanoid.
abstract: Anesthesia-related postoperative cognitive dysfunction (POCD) leads to morbidity in the elderly. Lipid peroxidative byproducts (i.e. acrolein) accumulate in aging and may play a role. Sevoflurane, an inhaled anesthetic, sequesters acrolein and enhances the formation of a serotonin-derived melanoid (SDM). SDM may be a biologically relevant polymeric melanoid that we previously showed exhibits redox activity and disrupts lipid bilayers. In this study, we examined the toxicity of SDM in cell culture and looked at protection using L-carnosine. SDM's toxic effects were tested on neuronal-like SH-SY5Y cells, causing an exponential decrease in viability, while human dermal fibroblasts were completely resistant to the toxic effects. SDM brought about morphological changes to differentiated SH-SY5Y cells, particularly to neuronal processes. Co- but not pre-treatment with L-carnosine protected differentiated SH-SY5Y cells exposed to SDM. Our mechanism suggests focal sevoflurane-induced sequestration of age-related acrolein leading to SDM synthesis and neuronal impairment, which is prevented by L-carnosine.
authors.affiliation: Department of Anesthesiology, University of Missouri-Kansas City School of Medicine, 4401 Wornall Road, Kansas City, MO 64111, USA.
authors.forename: Tanner D
authors.initials: TD
authors.lastname: Brownrigg
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Theisen
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Fibuch
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Seidler
mesh_terms: D000171:Acrolein / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008543:Melanins / Q000633:toxicity*; D008738:Methyl Ethers / Q000494:pharmacology; D009447:Neuroblastoma; D010084:Oxidation-Reduction; D012701:Serotonin / Q000378:metabolism*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008543:Melanins; D008738:Methyl Ethers; C014121:neuromelanin; D012701:Serotonin; D000077149:Sevoflurane; D000171:Acrolein; D002336:Carnosine