Influence of NF-κB on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication

Mykytenko, A. О.; Akimov, O. Ye.; Yeroshenko, G. А.; Neporada, K. S.

doi:10.15407/ubj94.06.057

Cited by 11 publications

(6 citation statements)

References 34 publications

(43 reference statements)

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“…Варто зазначити, що блокада активації транскрипційного фактора NF-κB може мати негативні наслідки для деяких органів та систем, оскільки здатна вплинути на перебіг багатьох окисно-відновних реакцій. Для прикладу може порушитись детоксикація ксенобіотичних сполук у печінці внаслідок зниження активності процесів мікросомального окиснення, де для знешкодження ксенобіотиків застосовуються активні форми кисню (АФК) [4]. Високоселективні інгібітори активації транскрипційного фактора NF-κB, такі як амоній піролідиндитіокарбамат (ПДТК), мають здатність індукувати апоптоз та зупиняти клітинний цикл [5].…”

Section: вступunclassified

“…МетС моделювали протягом 60 днів [6]. Третя групагрупа введення ПДТК в дозі 76 мг/кг в/о 3 рази на тиждень протягом 60 діб (група ПДТК) [4]. Че-тверта група -група поєднаного впливу введення ПДТК в дозі 76 мг/кг в/о 3 рази на тиждень протягом 60 діб та відтворення МетС (ПДТК+МетС).…”

Section: матеріали та методиunclassified

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Effect of Ammonium Pyrrolidinedithiocarbamate on the Development of Oxidative Stress in Biceps Femoris Muscles of Rats During Modelled Metabolic Syndrome

Akimov,

Mykytenko,

Mischenko

et al. 2024

Act. Probl. of the Modern Med.

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Excessive consumption of high-calorie food, a sedentary lifestyle and increased psycho-emotional stress are risk factors for the development of metabolic syndrome. These factors are especially relevant for residents of countries with highly developed economies. Metabolic syndrome is accompanied not only by metabolic disorders, but also leads to the development of a systemic inflammatory response, which is associated with excessive production and circulation of cytokines in the blood. As a rule, the activation of the transcription factor NF-κB leads to an increase in the production of pro-inflammatory cytokines. The aim of this work is to determine the effect of the NF-κB transcription factor activation inhibitor on the activity of antioxidant enzymes, the production of superoxide anion radical, the content of oxidatively modified proteins, and the concentration of malondialdehyde in the biceps femoris muscle of rats who underwent experimental metabolic syndrome. The study included 24 sexually mature male Wistar rats weighing 200-260 g. The animals were divided into 4 groups of 6 animals each. The first group was the control group; the second group involved the rats exposed to metabolic syndrome simulated by adding a 20% fructose solution as the only source of drinking water to the standard vivarium diet for 60 days; the third group involved the animals received ammonium pyrrolidine dithiocarbamate in a dose of 76 mg/kg intraperitoneally 3 times a week for 60 days; the fourth group was exposed to the combined effect of the ammonium pyrrolidinedithiocarbamate administration during modeled metabolic syndrome. In this study we investigated a 10% homogenate of the biceps femoris muscle with the research focus on several parameters: superoxide anion radical production, superoxide dismutase and catalase activity, malondialdehyde concentration, and the presence of oxidatively modified proteins. Simulation of the metabolic syndrome led to the development of oxidative stress in the biceps muscle of rats that was accompanied by an increase in the production of the superoxide anion radical and a decrease in the activity of antioxidant enzymes. The administration of ammonium pyrrolidinedithiocarbamate during modeled metabolic syndrome caused a decrease in the basic production of superoxide anion radical, production of superoxide anion radical by the microsomal electron transport chain and production of superoxide anion radical by the mitochondrial electron transport chain by 30.28%, 26.21 %, and 27.00%, respectively, compared to the rats in metabolic syndrome group. Superoxide dismutase activity increased by 78.81% and catalase activity grew by 144.74% compared to the metabolic syndrome group. The concentration of free malondialdehyde under the administration of ammonium pyrrolidinedithiocarbamate during metabolic syndrome reduced by 51.80%, and the content of oxidatively modified proteins decreased by 31.74% compared to the metabolic syndrome group. The administration of ammonium pyrrolidinedithiocarbamate, an NF-κB transcription factor activation inhibitor, effectively prevents the development of oxidative stress in the biceps femoris muscle of rats with modeled metabolic syndrome. This study is a part of the initiative research project No. 0124U000092 "High- and low-intensity phenotypes of systemic inflammatory response: molecular mechanisms and new medical technologies for their prevention and correction".

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Section: вступunclassified

Section: матеріали та методиunclassified

Effect of Ammonium Pyrrolidinedithiocarbamate on the Development of Oxidative Stress in Biceps Femoris Muscles of Rats During Modelled Metabolic Syndrome

Akimov,

Mykytenko,

Mischenko

et al. 2024

Act. Probl. of the Modern Med.

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“…Відомо, що оксидативно-нітрозативний стрес відіграє ключову роль у патофізіології хронічної алкогольної інтоксикації (ХАІ) [4,5]. Метааналіз результатів сучасних клінічних досліджень виявив, пацієнти з алкогольною залежністю мають істотно нижчу активність антиоксидантних ферментів (супероксиддисмутази і глутатіонпероксидази), тоді як концентрація вторинного продукту пероксидного окиснення ліпідів малонового діальдегіду в зразках сироватки / плазми крові є достовірно підвищеними [6].…”

Section: вступunclassified

“…Як молекулярні патерни, що асоційовані з ушкодженням (англ. Damage-Associated Molecular Patterns, DAMPs), що вивільняються при травматичному процесі, так і етанол, можуть спричинити збільшення активності транскрипційного фактора NF-κB [5,18,19]. Наслідком цього є індукція прозапальних та прооксидантних генів, включаючи iNOS, з подальшою продукцією АФО / АФН, зміною окисно-відновного стану тканин, що посилює позитивний зворотний зв'язок між цими змінами та активацією редоксчутливих факторів транскрипції [20].…”

Section: обговорення результатів дослідженняunclassified

IMPACT OF NF-κB AND NRF2 TRANSCRIPTION FACTOR MODULATORS ON METABOLIC CHARACTERISTICS IN MANDIBLE BONES OF RATS DURING RECOVERY FROM INCOMPLETE FRACTURE UNDER CHRONIC ALCOHOL INTOXICATION

Nestulia,

Kostenko

2024

Act. Probl. of the Modern Med.

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This study aims at investigating the influence of specific modulators of NF-κB and Nrf2 transcription factors on oxidative-nitrosative stress indicators and bone biopolymer depolymerization in mandibular bone following incomplete fracture under chronic alcohol intoxication (CAI). Twenty-eight white male Wistar rats were divided into five groups: Group 1 comprised "falsely injured" rats, while Group 2 underwent incomplete mandibular fracture (IMF) under CAI exposure. Rats in groups 3 and 4 received intraperitoneal injections of ammonium pyrrolidinium dithiocarbamate, an inhibitor of NF-κB activation, in a dose of 76 mg/kg, and dimethyl fumarate, an Nrf2 inducer, in a dose of 15 mg/kg three times a week for 14 days following the modeling of IMF under CAI exposure. The activity of total NO synthase, including its constitutive and inducible isoforms, along with ornithine decarboxylase, and concentrations of peroxynitrites of alkaline and alkaline-earth metals, free hydroxyproline, N-acetylneuraminic, and hexuronic acids were assessed in the homogenate of the standard mandible area using a spectrophotometric method. The findings have demonstrated that the administration of ammonium pyrrolidine dithiocarbamate and dimethyl fumarate notably decreased the activity of NO synthase (primarily its inducible isoform) and the concentration of peroxynitrite in the mandibular bone homogenate, while increasing the activity of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. Furthermore, under experimental conditions, the use of ammonium pyrrolidine dithiocarbamate and dimethyl fumarate limited the depolymerization of bone biopolymers (collagen, glycoproteins, and proteoglycans), thereby facilitating effective reparative osteogenesis.

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“…25 The concentration of nitrite and peroxynitrite of alkali and alkaline earth metals, the activity of nitriteand nitrate reductases, arginases, superoxide dismutase (SOD) and catalase, concentration of malondialdehyde (MDA), oxidation-modified proteins and production of superoxide anion, GAG fractions (heparin-heparan, keratan-dermatan and chondroitin), the concentration of free oxyproline and sialic acids were studied in rat liver 10% homogenate. 23,[26][27][28][29][30][31][32][33]…”

Section: Biochemical Analysismentioning

confidence: 99%

Role of sulfide anion in the development of chronic alcoholic hepatitis under the conditions of modulation of adenosine monophosphate kinase – a correlational study

Mykytenko,

Akimov,

Shevchenko

et al. 2023

Eur J Clin Exp Med

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Introduction and aim. Hydrogen sulfide (H 2 S) has attracted the attention of researchers as a novel signaling molecule that affects vascular metabolism, immune function, stress and inflammation. It plays an important role in pathophysiological disorders under the conditions of the development of obesity, diabetes, non-alcoholic fatty liver disease and cardiovascular diseases. The purpose of this work is to establish correlation ratios of H 2 S concentration with markers of oxidative-nitrosative stress and extracellular matrix metabolism of the liver during chronic alcoholic hepatitis modeling and AMPK modulation by phenformin and doxorubicin. Material and methods. The experiments were performed on 36 white, sexually mature male Wistar rats, weighing 180-220 g. Alcoholic hepatitis was modelled by alcohol administration, on the background of alcoholic hepatitis animals received phenformin orally at a dose of 10 mg/kg or doxorubicin at a dose of 1.25 mg/kg intraperitoneally. Statistical processing of the results of biochemical studies was carried out using the non-parametric method of Spearman to determine correlations. Results. H 2 S during alcoholic hepatitis inversely proportionally strongly correlates with the concentration of nitrites, oxyproline and arginase activity. Phenformin administration during alcoholic hepatitis leads to formation of inversely proportionally strongly correlation of H 2 S with the production of superoxide anion radical, the concentration of malondialdehyde, activities of constitutive NO-synthases, nitrite reductases, nitrate reductases, and arginase. Doxorubicin administration during alcoholic hepatitis leads to formation of directly proportional strongly correlation of H 2 S with the activity of constitutive NO-synthases, nitrite reductases, nitrate reductases. Conclusion. Administration of phenformin or doxorubicin expands correlations between H 2 S and indicators of oxidative-nitrosative stress.

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Influence of NF-κB on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication

Cited by 11 publications

References 34 publications

Effect of Ammonium Pyrrolidinedithiocarbamate on the Development of Oxidative Stress in Biceps Femoris Muscles of Rats During Modelled Metabolic Syndrome

Effect of Ammonium Pyrrolidinedithiocarbamate on the Development of Oxidative Stress in Biceps Femoris Muscles of Rats During Modelled Metabolic Syndrome

IMPACT OF NF-κB AND NRF2 TRANSCRIPTION FACTOR MODULATORS ON METABOLIC CHARACTERISTICS IN MANDIBLE BONES OF RATS DURING RECOVERY FROM INCOMPLETE FRACTURE UNDER CHRONIC ALCOHOL INTOXICATION

Role of sulfide anion in the development of chronic alcoholic hepatitis under the conditions of modulation of adenosine monophosphate kinase – a correlational study

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