Jan Homolak1,2, Ana Babic Perhoc1,2, Ana Knezovic1,2, Ivan Kodvanj1,2, Davor Virag1,2, Jelena Osmanovic Barilar1,2, Peter Riederer3,4, Melita Salkovic-Petrisic1,2. 1. Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia. 2. Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia. 3. Clinic and Polyclinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany. 4. University of Southern Denmark Odense, Odense, Denmark.
Abstract
SCOPE: 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). METHODS AND RESULTS: Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg-1 ). 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. CONCLUSION: 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.
SCOPE: 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). METHODS AND RESULTS: Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg-1 ). 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. CONCLUSION: 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.
Authors: Jan Homolak; Ivan Kodvanj; Ana Babic Perhoc; Davor Virag; Ana Knezovic; Jelena Osmanovic Barilar; Peter Riederer; Melita Salkovic-Petrisic Journal: MethodsX Date: 2021-12-22