Delaying latency to hyperbaric oxygen-induced CNS oxygen toxicity seizures by combinations of exogenous ketone supplements.

Autor: Ari C; Department of Psychology, Hyperbaric Neuroscience Research Laboratory, University of South Florida, Tampa, Florida., Koutnik AP; Department of Molecular Pharmacology and Physiology, Laboratory of Metabolic Medicine, University of South Florida, Tampa, Florida., DeBlasi J; Department of Molecular Pharmacology and Physiology, Laboratory of Metabolic Medicine, University of South Florida, Tampa, Florida., Landon C; Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, University of South Florida, Tampa, Florida., Rogers CQ; Department of Molecular Pharmacology and Physiology, Laboratory of Metabolic Medicine, University of South Florida, Tampa, Florida., Vallas J; Department of Psychology, Hyperbaric Neuroscience Research Laboratory, University of South Florida, Tampa, Florida., Bharwani S; Department of Psychology, Hyperbaric Neuroscience Research Laboratory, University of South Florida, Tampa, Florida., Puchowicz M; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee., Bederman I; Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio.; Department of Nutrition, Case Western Reserve University, Cleveland, Ohio., Diamond DM; Department of Psychology, Hyperbaric Neuroscience Research Laboratory, University of South Florida, Tampa, Florida.; Department of Molecular Pharmacology and Physiology, Laboratory of Metabolic Medicine, University of South Florida, Tampa, Florida., Kindy MS; Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida.; James A. Haley VA Medical Center, Tampa, Florida.; Shriners Hospital for Children, Tampa, Florida., Dean JB; Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, University of South Florida, Tampa, Florida., D Agostino DP; Department of Molecular Pharmacology and Physiology, Laboratory of Metabolic Medicine, University of South Florida, Tampa, Florida.; Institute for Human and Machine Cognition, Ocala, Florida.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2019 Jan; Vol. 7 (1), pp. e13961.
DOI: 10.14814/phy2.13961
Abstrakt: Central nervous system oxygen toxicity (CNS-OT) manifests as tonic-clonic seizures and is a limitation of hyperbaric oxygen therapy (HBOT), as well as of recreational and technical diving associated with elevated partial pressure of oxygen. A previous study showed that ketone ester (1,3-butanediol acetoacetate diester, KE) administration delayed latency to seizures (LS) in 3-month-old Sprague-Dawley (SD) rats. This study explores the effect of exogenous ketone supplements in additional dosages and formulations on CNS-OT seizures in 18 months old SD rats, an age group correlating to human middle age. Ketogenic agents were given orally 60 min prior to exposure to hyperbaric oxygen and included control (water), KE (10 g/kg), KE/2 (KE 5 g/kg + water 5 g/kg), KE + medium-chain triglycerides (KE 5 g/kg + MCT 5 g/kg), and ketone salt (Na + /K + βHB, KS) + MCT (KS 5 g/kg + MCT 5 g/kg). Rats were exposed to 100% oxygen at 5 atmospheres absolute (ATA). Upon seizure presentation (tonic-clonic movements) experiments were immediately terminated and blood was tested for glucose and D-beta-hydroxybutyrate (D-βHB) levels. While blood D-βHB levels were significantly elevated post-dive in all treatment groups, LS was significantly delayed only in KE (P = 0.0003), KE/2 (P = 0.023), and KE + MCT (P = 0.028) groups. In these groups, the severity of seizures appeared to be reduced, although these changes were significant only in KE-treated animals (P = 0.015). Acetoacetate (AcAc) levels were also significantly elevated in KE-treated animals. The LS in 18-month-old rats was delayed by 179% in KE, 219% in KE + MCT, and 55% in KE/2 groups, while only by 29% in KS + MCT. In conclusion, KE supplementation given alone and in combination with MCT elevated both βHB and AcAc, and delayed CNS-OT seizures.
(© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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