{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:09:20Z","timestamp":1792789760312,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ELTE BDPK Excellence Program","award":["12\/2021"],"award-info":[{"award-number":["12\/2021"]}]},{"name":"ELTE BDPK Excellence Program","award":["12\/2022"],"award-info":[{"award-number":["12\/2022"]}]},{"name":"ELTE BDPK Excellence Program","award":["12\/2023"],"award-info":[{"award-number":["12\/2023"]}]},{"name":"ELTE BDPK Excellence Program","award":["12\/2021"],"award-info":[{"award-number":["12\/2021"]}]},{"name":"Ketone Technologies LLC","award":["12\/2021"],"award-info":[{"award-number":["12\/2021"]}]},{"name":"Ketone Technologies LLC","award":["12\/2022"],"award-info":[{"award-number":["12\/2022"]}]},{"name":"Ketone Technologies LLC","award":["12\/2023"],"award-info":[{"award-number":["12\/2023"]}]},{"name":"Ketone Technologies LLC","award":["12\/2021"],"award-info":[{"award-number":["12\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>It has been demonstrated that isoflurane-induced anesthesia can increase the blood glucose level, leading to hyperglycemia and several adverse effects. The administration of a mix of ketone diester (KE) and medium-chain triglyceride (MCT) oil, named KEMCT, abolished the isoflurane-anesthesia-induced increase in blood glucose level and prolonged the recovery time from isoflurane anesthesia in a male preclinical rodent model, Wistar Albino Glaxo\/Rijswijk (WAG\/Rij) rats. While most preclinical studies use exclusively male animals, our previous study on blood glucose changes in response to KEMCT administration showed that the results can be sex-dependent. Thus, in this study, we investigated female WAG\/Rij rats, whether KEMCT gavage (3 g\/kg\/day for 7 days) can change the isoflurane (3%)-anesthesia-induced increase in blood glucose level and the recovery time from isoflurane-evoked anesthesia using the righting reflex. Moreover, KEMCT-induced ketosis may enhance both the extracellular level of adenosine and the activity of adenosine A1 receptors (A1Rs). To obtain information on the putative A1R mechanism of action, the effects of an A1R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine; intraperitoneal\/i.p. 0.2 mg\/kg), on KEMCT-generated influences were also investigated. Our results show that KEMCT supplementation abolished the isoflurane-anesthesia-induced increase in blood glucose level, and this was abrogated by the co-administration of DPCPX. Nevertheless, KEMCT gavage did not change the recovery time from isoflurane-induced anesthesia. We can conclude that intragastric gavage of exogenous ketone supplements (EKSs), such as KEMCT, can abolish the isoflurane-anesthesia-induced increase in blood glucose level in both sexes likely through A1Rs in WAG\/Rij rats, while recovery time was not affected in females, unlike in males. These results suggest that the administration of EKSs as an adjuvant therapy may be effective in mitigating metabolic side effects of isoflurane, such as hyperglycemia, in both sexes.<\/jats:p>","DOI":"10.3390\/nu16101477","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T06:28:12Z","timestamp":1715668092000},"page":"1477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exogenous Ketone Supplement Administration Abrogated Isoflurane-Anesthesia-Induced Increase in Blood Glucose Level in Female WAG\/Rij Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Enik\u0151","family":"Rauch","sequence":"first","affiliation":[{"name":"Department of Biology, Berzsenyi D\u00e1niel Teacher Training Centre, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, K\u00e1rolyi G\u00e1sp\u00e1r t\u00e9r 4, 9700 Szombathely, Hungary"},{"name":"Institute of Biology, University of P\u00e9cs, Ifj\u00fas\u00e1g Str. 6, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-823X","authenticated-orcid":false,"given":"Csilla","family":"Ari","sequence":"additional","affiliation":[{"name":"Ketone Technologies LLC, Tampa, FL 33612, USA"},{"name":"Behavioral Neuroscience Research Laboratory, Department of Psychology, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-181X","authenticated-orcid":false,"given":"Dominic P.","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Ketone Technologies LLC, Tampa, FL 33612, USA"},{"name":"Laboratory of Metabolic Medicine, Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"},{"name":"Institute for Human and Machine Cognition, Ocala, FL 34471, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5686","authenticated-orcid":false,"given":"Zsolt","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Biology, Berzsenyi D\u00e1niel Teacher Training Centre, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, K\u00e1rolyi G\u00e1sp\u00e1r t\u00e9r 4, 9700 Szombathely, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nrn2372","article-title":"General anaesthesia: From molecular targets to neuronal pathways of sleep and arousal","volume":"9","author":"Franks","year":"2008","journal-title":"Nat. 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