Lipidomics reveals a systemic energy deficient state that precedes neurotoxicity in neonatal monkeys after sevoflurane exposure.

Abstract

Although numerous studies have raised public concerns regarding the safety of anesthetics including sevoflurane in children, the biochemical mechanisms leading to anesthetics-induced neurotoxicity remain elusive. Moreover, potential biomarker(s) for early detection of general anesthetics-induced brain injury are urgent for public health. We employed an enabling technology of shotgun lipidomics and analyzed nearly 20 classes and subclasses of lipids present in the blood serum of postnatal day (PND) 5 or 6 rhesus monkeys temporally collected after exposure to sevoflurane at a clinically relevant concentration or room-air as control. Lipidomics analysis revealed numerous significant anesthetic-induced changes of serum lipids and their metabolites as well as short chain acylcarnitines in the brain and cerebrospinal fluid after anesthetic exposure. These include decreased carnitine and acylcarnitines, unchanged triacylglycerol mass but accumulation of 16:0 and 18:1 fatty acyl chains in the triacylglycerol pool, losses of polyunsaturated fatty acids in both non-esterified fatty acid and phospholipid pools, and increased 4-hydroxynonenal content as early as 2 h after sevoflurane exposure. Importantly, the amounts of short chain acylcarnitines in the brain and cerebrospinal fluid were also significantly reduced after anesthetic exposure. We propose that this serum lipidomic profile can serve as indicative of neuronal damage. Our results reveal that sevoflurane exposure induces an energy deficient state in the brain evidenced by reduced free and acyl carnitine contents, as well as the presence of a pro-inflammatory state in the exposed animals, providing deep insights into the underlying mechanisms responsible for anesthetic-induced neurotoxicity.

• Authors: Chunyan Wang, Fang Liu, Jessica L Frisch-Daiello, Shannon Martin, Tucker A Patterson, Qiang Gu, Shuliang Liu, Merle G Paule, Joseph P Hanig, William Slikker Jr, Peter A Crawford, Cheng Wang, Xianlin Han
• Journal: Analytica chimica acta (Anal Chim Acta) Vol. 1037 Pg. 87-96 (Dec 11 2018) ISSN: 1873-4324 [Electronic] Netherlands
• PMID: 30292318 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Sevoflurane

Topics

• Animals
• Energy Metabolism (drug effects)
• Lipid Metabolism (drug effects)
• Macaca mulatta
• Neurons (drug effects)
• Sevoflurane (pharmacology)