Metabolomic Profiling Reveals Differences in Hypoxia Response between Far Eastern and Siberian Frogs

SIMPLE SUMMARY: The lack of oxygen is a significant challenge for most animals, which can lead to tissue damage and death. The Siberian frog Rana amurensis is so far the only known amphibian capable of surviving water anoxia for a long time. We compared metabolomic profiles of the liver, brain, and heart under hypoxia for the Siberian frog and the Far Eastern (Rana dybowskii) frog, which is highly susceptible to the lack of oxygen. One of the most interesting findings was that the organs of the Far Eastern frog had more lactate (glycolysis end product) than those of the Siberian frog despite a much shorter exposure time. The amounts of succinate were similar between the two species. Interestingly, glycerol and 2,3-butanediol were found to be abundant under hypoxia in the Siberian frog, but not in the Far Eastern frog. The role of these substances are still unclear. Based on the obtained data, we suggest a bioenergetic pathway for metabolic changes in the Siberian frog under anoxia. ABSTRACT: Anoxia is a significant challenge for most animals, as it can lead to tissue damage and death. Among amphibians, the Siberian frog Rana amurensis is the only known species capable of surviving near-zero levels of oxygen in water for a prolonged period. In this study, we aimed to compare metabolomic profiles of the liver, brain, and heart of the Siberian frog exposed to long-term oxygen deprivation (approximately 0.2 mg/L water) with those of the susceptible Far Eastern frog (Rana dybowskii) subjected to short-term hypoxia to the limits of its tolerance. One of the most pronounced features was that the organs of the Far Eastern frog contained more lactate than those of the Siberian frog despite a much shorter exposure time. The amounts of succinate were similar between the two species. Interestingly, glycerol and 2,3-butanediol were found to be significantly accumulated under hypoxia in the Siberian frog, but not in the Far Eastern frog. The role and biosynthesis of these substances are still unclear, but they are most likely formed in certain side pathways of glycolysis. Based on the obtained data, we suggest a pathway for metabolic changes in the Siberian frog under anoxia.