Department of Biology, Berzsenyi Dániel Teacher Training Centre, ELTE Eötvös Loránd University, Károlyi Gáspár tér 4, 9700 Szombathely, Hungary.
Institute of Biology, University of Pécs, Ifjúság Str. 6, 7624 Pécs, Hungary.
Nutrients. 2024 May 14;16(10):1477. doi: 10.3390/nu16101477.
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.
已证实，异氟烷诱导的麻醉会导致血糖升高，引发高血糖和多种不良反应。在雄性临床前啮齿动物模型（Wistar Albino Glaxo/Rijswijk（WAG/Rij）大鼠）中，给予混合酮二酯（KE）和中链甘油三酯（MCT）油的混合物（称为 KEMCT），可消除异氟烷麻醉引起的血糖升高，并延长异氟烷麻醉的恢复时间。虽然大多数临床前研究仅使用雄性动物，但我们之前关于 KEMCT 给药后血糖变化的研究表明，结果可能存在性别依赖性。因此，在这项研究中，我们研究了雌性 WAG/Rij 大鼠，KEMCT 灌胃（3 克/千克/天，持续 7 天）是否可以改变异氟烷（3%）麻醉引起的血糖升高以及恢复时间从异氟烷诱发的麻醉用翻正反射。此外，KEMCT 诱导的酮症可能会增加细胞外腺苷水平和腺苷 A1 受体（A1R）的活性。为了获得关于假定的 A1R 作用机制的信息，还研究了 A1R 拮抗剂 DPCPX（1,3-二丙基-8-环戊基黄嘌呤；腹腔内/i.p.0.2 毫克/千克）对 KEMCT 产生的影响。我们的结果表明，KEMCT 补充剂可消除异氟烷麻醉引起的血糖升高，而这种作用可被 DPCPX 共同给药所阻断。然而，KEMCT 灌胃并未改变异氟烷诱导的麻醉恢复时间。我们可以得出结论，通过 WAG/Rij 大鼠中的 A1R，胃内灌胃外源性酮补充剂（EKS），如 KEMCT，可消除异氟烷麻醉引起的血糖升高，而在女性中，恢复时间不受影响，而在男性中则受影响。这些结果表明，作为辅助治疗，EKS 的给药可能在两性中都有效，可减轻异氟烷引起的代谢副作用，如高血糖。
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