Liver mitochondrial respiratory plasticity and oxygen uptake evoked by cobalt chloride in rats with low and high resistance to extreme hypobaric hypoxia

Abstract

High-altitude intolerance and consequently high-altitude sickness, is difficult to predict. Liver is an essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity, and respiratory coupling. We determined the cobalt chloride (CoCl2) effects on liver mitochondrial plasticity and oxygen uptake in rats with low resistance (LR) and high resistance (HR) to extreme hypobaric hypoxia. The polarographic method proposed by Chance and Williams was used as a simple and effective tool to trace mitochondrial functionality and oxygen consumption. HR rats had more efficient processes of NADH- and FAD-generated mitochondrial oxidation. CoCl2 promoted more efficient NADH-generated and diminished less efficient FAD-generated mitochondrial respiratory reactions in HR rats. CoCl2 diminished both aerobic and anaerobic processes in LR rats. Glutamate and pyruvate substrates of NADH-generated mitochondrial pathways were highly affected by CoCl2. Red blood cells acted as cobalt depots in HR and LR rats. We have unveiled several mechanisms leading to differentiated mitochondrial respiratory responses to hypobaric hypoxia in LR and HR rats. Our study strongly supports the existence of adaptive liver mitochondrial plasticity to extreme hypoxia.

Mechanisms of Adverse Local Tissue Reactions to Hip Implants

“…This happens not as the result of the inhibition of ATP synthase or the respiratory chain, but as consequence of the opening of the mitochondrial permeability transition pore (MPT), which allows the H + to migrate from the intermembrane space to the mitochondria matrix, thus decreasing the electromotive force that activates the ATP synthase (Figure 8A) (Bragadin et al, 2007). As a consequence of this aerobic respiration failure, the production of ATP is decreased, and the anaerobic pathway for ATP generation is stimulated (Kurhaluk et al, 2019). This opening of MPT pore induced by cobalt also decreases the pool of NADH and NADPH in rat liver mitochondria, and may “leak” antioxidant proteins from the mitochondrial matrix (Battaglia et al, 2009).…”

Differences in Tolerance to Hypoxia: Physiological, Biochemical, and Molecular-Biological Characteristics

“…Clinical and pathophysiological studies, focused on the research on the effect of high-altitude conditions on the organism, made it possible to distinguish two polar groups of laboratory animals and humans according to their ability to adapt to the lack of oxygen and differences in their basic resistance to hypoxia [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. In experimental studies, according to the results of the survival time (the time before respiratory disturbances and signs of asphyxia appear) in an assessment under conditions of hypobaric hypoxia, animals are divided into tolerant and susceptible to oxygen deficiency.…”

“…One of the most common methods for determining tolerance to oxygen deficiency is a model that reproduces the conditions of hypobaric hypoxia in decompression chambers, into which volunteers, pilots, astronauts or experimental animals are set [ 9 , 10 , 11 , 12 , 14 , 17 , 18 , 19 , 20 , 21 , 22 , 123 , 124 , 125 , 126 , 127 , 128 , 129 ]. To assess the individual’s hypoxia tolerance, people are exposed to altitudes of several thousand meters [ 99 , 101 , 130 ].…”

“…The determination of the hypoxia tolerance of animals, as a rule, is carried out once and the experiment is performed immediately after the exposure, after an hour, a week, two weeks, three weeks or a month [ 9 , 11 , 12 , 14 , 17 , 20 , 21 , 22 , 126 , 127 , 192 , 197 , 198 , 199 ]. Some authors carry out the test several times at some intervals; for example, three times with a one-week interval [ 11 , 12 , 14 , 127 ].…”

“…Oxygen deficiency is one of the key factors in the development of infectious, inflammatory, and tumor diseases [ 1 , 2 , 3 , 4 , 5 , 6 ]. It is known that basic tolerance to hypoxia in humans and various animal species differs [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. The differences in basic tolerance to oxygen deficiency can determine the predisposition to the development of hypoxia-related disorders.…”