Kurhaluk Natalia, Lukash Oleksandr, Tkaczenko Halina
Institute of Biology, Pomeranian University in Słupsk, Arciszewski Str. 22b, Słupsk, Poland, E-Mail:
Department of Ecology, Geography and Nature ManagementT.G. Shevchenko National University "Chernihiv Colehium"53 Hetmana Polubotka Street, Chernihiv, 14013, Ukraine.
Cell Physiol Biochem. 2023 Nov 15;57(6):426-451. doi: 10.33594/000000669.
BACKGROUND/AIMS: Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates.
A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent.
Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O in N, 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O in N, 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL.
The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines.
背景/目的：目前已证实，一氧化氮的细胞代谢对于维持机体的最佳健康状态以及使其适应各种环境因素的影响是必要的。本研究的目的是揭示一氧化氮在低氧条件下组织中的生物学作用、其代谢变化及其作用机制，以及在克雷布斯循环中间体的影响下通过一氧化氮依赖性系统纠正组织代谢的可能性。
评估了琥珀酸盐（SC，50mg/kg体重）和α-酮戊二酸（KGL，50mg/kg体重）对大鼠氧依赖过程（线粒体氧化磷酸化、微粒体氧化、脂质过氧化过程强度和抗氧化防御系统状态）的调节作用，这些过程取决于低氧期间一氧化氮生成的功能变化。通过测定其稳定的亚硝酸根阴离子代谢物（NO-）的浓度，用分光光度法评估一氧化氮系统的状态。使用差分荧光法根据肾上腺素和去甲肾上腺素的含量估算儿茶酚胺的水平。用纳什试剂测定细胞色素P450依赖性氨基比林-N-脱甲基酶的活性。
在急性低氧（AH，氮气中7%氧气，30分钟）条件下，通过儿茶酚胺（肾上腺素、去甲肾上腺素、多巴胺、多巴）以及胆碱酯酶相关系统（乙酰胆碱含量和乙酰胆碱酯酶活性）含量的变化所导致的组织低氧和代谢紊乱是研究的实验参数。AH中脂质过氧化和氧化修饰蛋白的激活以及肾上腺素含量的增加与SC作用的增强和KGL作为线粒体氧化底物的减少有关。与SC相比，在急性低氧背景下，外源性KGL对肝脏中作为一氧化氮稳定代谢物的亚硝酸根阴离子含量有更显著的影响，同时脂质过氧化过程强度降低。发现间歇性低氧训练（IHT）疗程后，AH引起的依赖SC的线粒体氧化过程的激活在动物中有所降低。IHT（氮气中7%氧气，15分钟，每天5次，共14天）可防止AH影响后组织和血液中氧化应激的激活，并通过增加KGL的氧化提高肝脏线粒体功能中能量相关反应的效率。
通过硝酸盐、亚硝酸盐、尿素和总多胺池的变化评估，所研究的适应效应是由一氧化氮依赖性机制作用的增强介导的。
