Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.
Institute of Physiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria.
Nutrients. 2021 Sep 29;13(10):3448. doi: 10.3390/nu13103448.
5-Hydroxymethylfurfural (5-HMF) is known to increase hemoglobin oxygen affinity (Hb-O affinity) and to induce a left shift of the oxygen dissociation curve (ODC). It is under investigation as a therapeutic agent in sickle cell anemia and in conditions where pulmonary oxygen uptake is deteriorated or limited (e.g., various clinical conditions or altitude exposure). The combination of 5-HMF and α-ketoglutaric acid (αKG) is commercially available as a nutritional supplement. To further elucidate dose effects, ODCs were measured in vitro in venous whole blood samples of 20 healthy volunteers (10 female and 10 male) after the addition of three different doses of 5-HMF, αKG and the combination of both. Linear regression analysis revealed a strong dose-dependent increase in Hb-O affinity for 5-HMF (R = 0.887; < 0.001) and the commercially available combination with αKG (R = 0.882; < 0.001). αKG alone increased Hb-O affinity as well but to a lower extent. Both the combination (5-HMF + αKG) and 5-HMF alone exerted different P50 and Hill coefficient responses overall and between sexes, with more pronounced effects in females. With increasing Hb-O affinity, the sigmoidal shape of the ODC was better preserved by the combination of 5-HMF and αKG than by 5-HMF alone. Concerning the therapeutic effects of 5-HMF, this study emphasizes the importance of adequate dosing in various physiological and clinical conditions, where a left-shifted ODC might be beneficial. By preserving the sigmoidal shape of the ODC, the combination of 5-HMF and αKG at low (both sexes) and medium (males only) doses might be able to better maintain efficient oxygen transport, particularly by mitigating potentially deteriorated oxygen unloading in the tissue. However, expanding knowledge on the interaction between 5-HMF and Hb-O affinity in vitro necessitates further investigations in vivo to additionally assess pharmacokinetic mechanisms.
5-羟甲基糠醛（5-HMF）已知会增加血红蛋白的氧亲和力（Hb-O 亲和力）并诱导氧离解曲线（ODC）向左移位。它正在作为镰状细胞贫血和肺部氧气摄取恶化或受限的情况下（例如，各种临床情况或海拔暴露）的治疗剂进行研究。5-HMF 和 α-酮戊二酸（αKG）的组合是商业上可用的营养补充剂。为了进一步阐明剂量效应，在 20 名健康志愿者（10 名女性和 10 名男性）的静脉全血样本中测量了体外 ODC，在添加三种不同剂量的 5-HMF、αKG 和两者的组合后。线性回归分析显示，5-HMF（R = 0.887；<0.001）和市售组合与 αKG（R = 0.882；<0.001）的 Hb-O 亲和力呈强剂量依赖性增加。αKG 单独也增加了 Hb-O 亲和力，但程度较低。组合（5-HMF + αKG）和 5-HMF 本身在整体和性别之间均表现出不同的 P50 和 Hill 系数反应，女性的影响更为明显。随着 Hb-O 亲和力的增加，5-HMF 和 αKG 的组合比 5-HMF 本身更好地保留了 ODC 的 S 形。关于 5-HMF 的治疗效果，本研究强调了在各种生理和临床条件下适当给药的重要性，其中 ODC 向左移位可能是有益的。通过保持 ODC 的 S 形，低剂量（两性）和中剂量（仅男性）的 5-HMF 和 αKG 组合可能能够更好地维持有效的氧气输送，特别是通过减轻组织中潜在恶化的氧气卸载。然而，为了进一步评估药代动力学机制，需要在体内进一步研究 5-HMF 与 Hb-O 亲和力之间的相互作用，以增加对体外相互作用的了解。
