Ukr.Biochem.J. 2022; Volume 94, Issue 6, Nov-Dec, pp. 57-66

doi: https://doi.org/10.15407/ubj94.06.057

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

13.02.2023   Uncategorized   No comments

A. O. Mykytenko1*, O. Ye. Akimov2, G. A. Yeroshenko3, K. S. Neporada1

1Department of Bioorganic and Biological Chemistry,
Poltava State Medical University, Poltava, Ukraine;
2Department of Pathophysiology, Poltava State Medical University, Poltava, Ukraine;
3Department of Medical Biology, Poltava State Medical University, Poltava, Ukraine;
*e-mail: mykytenkoandrej18@gmail.com

Received: 05 October 2022; Revised: 15 December 2022;
Accepted: 17 February 2023; Available on-line: 27 February 2023

Alcohol-related liver disease is the most common cause of liver disease worldwide. The purpose of this work is the establishment of the influence of the transcription factor κB on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication. The experiments were performed on 24 male Wistar rats weighing 180-220 g. The animals were divided into 4 groups of 6 animals: control; animals, which were administered NF-κB inhibitor, namely ammonium pyrrolidinedithio­carbamate (PDTC) at a dose of 76 mg/kg 3 times a week; animals, on which we simulated alcoholic hepatitis and group of combination of alcoholic hepatitis and NF-κB inhibitor. We determined in rat liver homogenate the following biochemical parameters: the activi­ty of NO synthase isoforms, superoxide dismutase and catalase activity, the concentration of malonic dialdehyde, the concentration of peroxynitrite, nitrites and nitrosothiols, concentration of sulfide anion and superoxide anion radical production. Chronic alcohol intoxication led to increased production of reactive oxygen and nitrogen species on the background of decreased antioxidant activity, thus intensifying lipid peroxidation in the liver. Blockade of the transcription factor κB during chronic alcohol intoxication despite an increase in antioxidant activity and decrease of reactive oxygen and nitrogen species production did not ameliorate oxidative damage to the liver. Blockade of activation of nuclear transcription factor κB in rat liver by PDTC reduced the risk of oxidative damage to hepatocytes, but did not reduce the risk of developing nitrosative damage to hepatocytes.

Keywords: , , , ,

References:

  1. Avila MA, Dufour JF, Gerbes AL, Zoulim F, Bataller R, Burra P, Cortez-Pinto H, Gao B, Gilmore I, Mathurin P, Moreno C, Poznyak V, Schnabl B, Szabo G, Thiele M, Thursz MR. Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting. Gut. 2020;69(4):764-780. PubMed, PubMedCentral, CrossRef
  2. Kim HG, Huang M, Xin Y, Zhang Y, Zhang X, Wang G, Liu S, Wan J, Ahmadi AR, Sun Z, Liangpunsakul S, Xiong X, Dong XC. The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice. J Hepatol. 2019;71(5):960-969. PubMed, PubMedCentral, CrossRef
  3. Petrella C, Carito V, Carere C, Ferraguti G, Ciafrè S, Natella F, Bello C, Greco A, Ralli M, Mancinelli R, Messina MP, Fiore M, Ceccanti M. Oxidative stress inhibition by resveratrol in alcohol-dependent mice. Nutrition. 2020;79-80:110783. PubMed, CrossRef
  4. Wang Y, Hu H, Yin J, Shi Y, Tan J, Zheng L, Wang C, Li X, Xue M, Liu J, Wang Y, Li Y, Li X, Liu F, Liu Q, Yan S. TLR4 participates in sympathetic hyperactivity Post-MI in the PVN by regulating NF-κB pathway and ROS production. Redox Biol. 2019;24:101186. PubMed, PubMedCentral, CrossRef
  5. Qin JD, Cao ZH, Li XF, Kang XL, Xue Y, Li YL, Zhang D, Liu XY, Xue YZ. Effect of ammonium pyrrolidine dithiocarbamate (PDTC) on NF-κB activation and CYP2E1 content of rats with immunological liver injury. Pharm Biol. 2014;52(11):1460-1466. PubMed, CrossRef
  6. Stepanov YuM, Didenko VI, Dynnik OB, Konenko IS, Oshmianskaia NYu, Galinsky AA. Association of morphological changes in the liver parenchyma and its rigidity under the conditions of the experimental modeling of alcoholic and toxic hepatitis. Journal of the NAMSU. 2017;23(3-4):196-204.
  7. National Research Council (US) Subcommittee on Laboratory Animal Nutrition. Nutrient Requirements of Laboratory Animals: Fourth Revised Edition, 1995. Washington (DC): National Academies Press (US); 1995. PubMed, CrossRef
  8. Mykytenko AO, Yeroshenko GA. Reaction of hemomicrocirculatory bed of rat liver and changes in the functional state of the nitric oxide cycle under the conditions of modeling alcoholic hepatitis. World Med Biol. 2020;16(73):194-200. CrossRef
  9. Brusov OS, Gerasimov AM, Panchenko LF. The influence of natural inhibitors of radical reactions on autooxidation of adrenaline. Bull Exp Biol Med. 1976;81(1):33-35. (In Russian). PubMed
  10. Korolyuk MA, Ivanova LI, Mayorova IG, Tokarev VE. A method of determining catalase activity. Lab Delo. 1988;(1):16-19. (In Russian). PubMed
  11. Gérard-Monnier D, Erdelmeier I, Régnard K, Moze-Henry N, Yadan JC, Chaudière J. Reactions of 1-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Analytical applications to a colorimetric assay of lipid peroxidation. Chem Res Toxicol. 1998;11(10):1176-1183. PubMed, CrossRef
  12. Yelins’ka AM, Akimov OYe, Kostenko VO. Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response. Ukr Biochem J. 2019;91(1):80-85. CrossRef
  13. Gaston B, Reilly J, Drazen JM, Fackler J, Ramdev P, Arnelle D, Mullins ME, Sugarbaker DJ, Chee C, Singel DJ, Loscalzo J, Stamler J. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci USA. 1993;90(23):10957-10961. PubMed, PubMedCentral, CrossRef
  14. Sugahara S, Suzuki M, Kamiya H, Yamamuro M, Semura H, Senga Y, Egawa M, Seike Y. Colorimetric Determination of Sulfide in Microsamples. Anal Sci. 2016;32(10):1129-1131. PubMed, CrossRef
  15. Kostenko VO, Tsebrzhins’kii OI. Production of superoxide anion radical and nitric oxide in renal tissues sutured with different surgical suture material. Fiziol Zh. 2000;46(5):56-62. (In Ukrainian). PubMed
  16. Mykytenko AO, Akimov OY, Neporada KS. Influence of lipopolysaccharide on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication. Fiziol Zh. 2022;68(2):29-35. CrossRef
  17. Yang W, Yuan W, Peng X, Wang M, Xiao J, Wu C, Luo L. PPAR γ/Nnat/NF- κ B Axis Involved in Promoting Effects of Adiponectin on Preadipocyte Differentiation. Mediators Inflamm. 2019;2019:5618023. PubMed, PubMedCentral, CrossRef
  18. Radi R. Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci USA. 2018;115(23):5839-5848. PubMed, PubMedCentral, CrossRef
  19. Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative Stress in Cancer. Cancer Cell. 2020;38(2):167-197. PubMed, PubMedCentral, CrossRef
  20. Matsytska YeK, Akimov OYe, Mykytenko AO. Influence of corvitin and metformin on biochemical changes in lacrimal glands of rats during water avoidance stress modeling. J Ophthalmol. 2022;(3):39–44. CrossRef
  21. Ahmad N, Ansari MY, Bano S, Haqqi TM. Imperatorin suppresses IL-1β-induced iNOS expression via inhibiting ERK-MAPK/AP1 signaling in primary human OA chondrocytes. Int Immunopharmacol. 2020;85:106612. PubMed, PubMedCentral, CrossRef
  22. Murphy B, Bhattacharya R, Mukherjee P. Hydrogen sulfide signaling in mitochondria and disease. FASEB J. 2019;33(12):13098-13125. PubMed, PubMedCentral, CrossRef
  23. Srinivasan MP, Bhopale KK, Caracheo AA, Kaphalia L, Loganathan G, Balamurugan AN, Rastellini C, Kaphalia BS. Differential cytotoxicity, ER/oxidative stress, dysregulated AMPKα signaling, and mitochondrial stress by ethanol and its metabolites in human pancreatic acinar cells. Alcohol Clin Exp Res. 2021;45(5):961-978. PubMed, PubMedCentral, CrossRef
  24. Silva J, Spatz MH, Folk C, Chang A, Cadenas E, Liang J, Davies DL. Dihydromyricetin improves mitochondrial outcomes in the liver of alcohol-fed mice via the AMPK/Sirt-1/PGC-1α signaling axis. Alcohol. 2021;91:1-9. PubMed, PubMedCentral, CrossRef
  25. Xu T, Guo J, Wei M, Wang J, Yang K, Pan C, Pang J, Xue L, Yuan Q, Xue M, Zhang J, Sang W, Jiang T, Chen Y, Xu F. Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the Beclin-1 pathway. JCI Insight. 2021;6(15):e138183. PubMed, PubMedCentral, CrossRef
  26. Zhong S, Li L, Liang N, Zhang L, Xu X, Chen S, Yin H. Acetaldehyde Dehydrogenase 2 regulates HMG-CoA reductase stability and cholesterol synthesis in the liver. Redox Biol. 2021;41:101919. PubMed, PubMedCentral, CrossRef
  27. Yoshii Y, Furukawa T, Saga T, Fujibayashi Y. Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis: overview and application. Cancer Lett. 2015;356(2 Pt A):211-216. PubMed, CrossRef
  28. Wang M, Ma LJ, Yang Y, Xiao Z, Wan JB. n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review. Crit Rev Food Sci Nutr. 2019;59(sup1):S116-S129. PubMed, CrossRef
  29. Zima T. Alcohol Abuse. EJIFCC. 2018;29(4):285-289. PubMed, PubMedCentral
  30. Lu Y, Cederbaum AI. Cytochrome P450s and Alcoholic Liver Disease. Curr Pharm Des. 2018;24(14):1502-1517. PubMed, PubMedCentral, CrossRef
  31. Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, Li C, Shen G, Zou B. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5(1):227. PubMed, PubMedCentral, CrossRef
  32. Abdelhamid AM, Elsheakh AR, Suddek GM, Abdelaziz RR. Telmisartan alleviates alcohol-induced liver injury by activation of PPAR-γ/ Nrf-2 crosstalk in mice. Int Immunopharmacol. 2021;99:107963. PubMed, CrossRef
  33. Tang J, Xu L, Zeng Y, Gong F. Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway. Int Immunopharmacol. 2021;91:107272. PubMed, CrossRef
  34. Sun X, Ye C, Deng Q, Chen J, Guo C. Contribution of glutaredoxin-1 to Fas s-glutathionylation and inflammation in ethanol-induced liver injury. Life Sci. 2021;264:118678. PubMed, CrossRef
  35. Ren X, Sengupta R, Lu J, Lundberg JO, Holmgren A. Characterization of mammalian glutaredoxin isoforms as S-denitrosylases. FEBS Lett. 2019;593(14):1799-1806. PubMed, CrossRef
  36. Bostelaar T, Vitvitsky V, Kumutima J, Lewis BE, Yadav PK, Brunold TC, Filipovic M, Lehnert N, Stemmler TL, Banerjee R. Hydrogen Sulfide Oxidation by Myoglobin. J Am Chem Soc. 2016;138(27):8476-8488. PubMed, PubMedCentral, CrossRef
  37. Liu Z, Wang X, Li L, Wei G, Zhao M. Hydrogen Sulfide Protects against Paraquat-Induced Acute Liver Injury in Rats by Regulating Oxidative Stress, Mitochondrial Function, and Inflammation. Oxid Med Cell Longev. 2020;2020:6325378. PubMed, PubMedCentral, CrossRef
  38. Grohmann M, Wiede F, Dodd GT, Gurzov EN, Ooi GJ, Butt T, Rasmiena AA, Kaur S, Gulati T, Goh PK, Treloar AE, Archer S, Brown WA, Muller M, Watt MJ, Ohara O, McLean CA, Tiganis T. Obesity Drives STAT-1-Dependent NASH and STAT-3-Dependent HCC. Cell. 2018;175(5):1289-1306.e20. PubMed, PubMedCentral, CrossRef
  39. Zhu Q, Li H, Xie X, Chen X, Kosuru R, Li S, Lian Q, Cheung CW, Irwin MG, Ge RS, Xia Z. Adiponectin Facilitates Postconditioning Cardioprotection through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation. Oxid Med Cell Longev. 2020;2020:4253457. PubMed, PubMedCentral, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.