Homolak Jan, Babic Perhoc Ana, Knezovic Ana, Kodvanj Ivan, Virag Davor, Osmanovic Barilar Jelena, Riederer Peter, Salkovic-Petrisic Melita
Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.
Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
Mol Nutr Food Res. 2021 Nov;65(21):e2100400. doi: 10.1002/mnfr.202100400. Epub 2021 Sep 9.
Galactose, a ubiquitous monosaccharide with incompletely understood physiology is often exploited for inducing oxidative-stress mediated aging in animals. Recent research demonstrates that galactose can conserve cellular function during periods of starvation and prevent/alleviate cognitive deficits in a rat model of sporadic Alzheimer's disease. The present aim is to examine the acute effects of oral galactose on the redox regulatory network (RRN).
Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg ). No systemic RRN disbalance is observed; however, a mild pro-oxidative shift accompanied by a paradoxical increment in tissue reductive capacity suggesting overcompensation of endogenous antioxidant systems is observed in the hippocampus. Galactose-induced increment of reductive capacity is accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1.
Based on the observed findings, and in the context of previous work on galactose, a hormetic hypothesis of galactose is proposed suggesting that the protective effects may be inseparable from its pro-oxidative action at the biochemical level.
半乳糖是一种普遍存在的单糖，其生理学机制尚未完全明确，常用于诱导动物体内氧化应激介导的衰老。最近的研究表明，半乳糖在饥饿期间可维持细胞功能，并预防/减轻散发性阿尔茨海默病大鼠模型中的认知缺陷。目前的目的是研究口服半乳糖对氧化还原调节网络（RRN）的急性影响。
在对大鼠进行急性灌胃给予半乳糖（200 mg/kg）后，分析大鼠血浆和海马体中的RRN。未观察到全身RRN失衡；然而，在海马体中观察到轻度的促氧化转变，同时伴有组织还原能力的反常增加，这表明内源性抗氧化系统存在过度补偿。半乳糖诱导的还原能力增加伴随着海马体中烟酰胺腺嘌呤二核苷酸磷酸池的膨胀，这表明通过解除对氧化戊糖磷酸途径通量的抑制、降低神经元活性以及上调Leloir途径守门酶半乳糖激酶-1来进行ROS解毒。
基于观察到的结果，并结合之前关于半乳糖的研究，提出了半乳糖的 hormetic 假说，表明其保护作用可能与其在生化水平上的促氧化作用不可分割。
