Deneysel Alkol Tüketimi Modelinde Böbrekteki NOS2 ve NF-κB’nin İmmünreaktivitesi

Year 2023, Volume: 76 Issue: 1, 17 - 23, 25.05.2023

Aslı Okan Oflamaz , Abdulhadi Cihangir Uğuz Osman Öztürks , Ece Eroğlu , Seher Yılmaz , Züleyha Doğanyiğit

https://doi.org/10.4274/atfm.galenos.2023.46873

Abstract

Objectives: The negative effects of alcohol on health have attracted attention in recent years. The most devastating complications of alcoholism, such as kidney damage, can be seen due to the continuous consumption of alcohol. Possible mechanisms by which alcohol may increase renal dysfunction have been expressed in the literature. Among these mechanisms, oxidative stress is thought to be a potential mechanism that affects kidney function. Nitric oxide synthase (NOS) and nuclear factor kappa B (NF-κB) levels, which have roles in oxidative stress and inflammation, may be at abnormal levels in the kidney in alcohol use disorder. This study aimed to evaluate the role of NOS and NF-κB molecules in the mechanism of kidney damage caused by alcohol use.

Materials and Methods: The immunoreactivity of NOS2 and NF-κB in kidney tissue was evaluated in an experimental model of acute and chronic alcohol intake in male and female rats (n=56). Groups, control female, control male, sham female, sham male, acute male model, acute female model, chronic female model and chronic male model. The acute and chronic model groups were given ethanol to induce alcohol intake. Immunohistochemical analyzes were performed for NOS2 and NF-κB expressions along with histopathological analysis in kidney tissues.

Results: It was observed that glomerulation degeneration, bleeding, vacuolization, and inflammation were increased in kidney tissues in all groups compared to control groups. In addition, NF-κB and NOS2 expressions were found to be significantly higher in the acute and chronic model groups compared to the control groups.

Conclusion: The presented findings reveal that the expression of NOS2, which is involved in oxidative stress, and NF-κB, which is involved in inflammation, increases kidney damage in acute and chronic alcohol intake. Therefore, NFκB and NOS2 proteins, which play a role in tissue damage, inflammation, and oxidative stress response, may be associated with alcohol-induced renal damage.

Keywords

Alcohol Consumption Model , NF-κB , NOS2 , Kidney , Oxidative Stress

Ethical Statement

Ethics Committee Approval: This study was carried out with ethical approval from Erciyes University Animal Experiments Local Ethics Committee (HAYDEK) (approval no: 21/059, date: 07.04.2021). Informed Consent: Animal experiment study. Peer-reviewed: Externally peer-reviewed.

Supporting Institution

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Thanks

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References

• 1. Witkiewitz K, Litten R, Leggio L. Advances in the science and treatment of alcohol use disorder. Sci Adv. 2019;5:eaax4043.
• 2. Dguzeh U, Haddad NC, Smith KTS, et al. Alcoholism: A Multi-Systemic Cellular Insult to Organs. Int J Environ Res Public Health. 201828;15:1083.
• 3. Varga ZV, Matyas C, Paloczi J, et al. Alcohol Misuse and Kidney Injury: Epidemiological Evidence and Potential Mechanisms. Alcohol Res. 2017;38:283-288.
• 4. Reynolds K, Gu D, Chen J, et al. Alcohol consumption and the risk of endstage renal disease among Chinese men. Kidney Int. 2008;73:870-876.
• 5. Buja A, Scafato E, Baggio B, et al. Renal impairment and moderate alcohol consumption in the elderly. Results from the Italian Longitudinal Study on 6. Pan CS, Ju TR, Lee CC, et al. Alcohol use disorder tied to development of chronic kidney disease: A nationwide database analysis. PLoS One. 2018;13:e0203410.
• 7. Maharjan J, Le S, Green-Saxena A, et al. Mortality, disease progression, and disease burden of acute kidney injury in alcohol use disorder subpopulation. Am J Med Sci. 2022;364:46-52.
• 8. Bagyánszki M, Krecsmarik M, De Winter BY, et al. Chronic alcohol consumption affects gastrointestinal motility and reduces the proportion of neuronal NOS-immunoreactive myenteric neurons in the murine jejunum. Anat Rec (Hoboken). 2010;293:1536-1542.
• 9. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33:829-837.
• 10. Lee J. Nitric oxide in the kidney : its physiological role and pathophysiological implications. Electrolyte Blood Press. 2008;6:27-34.
• 11. Sun H, Patel KP, Mayhan WG. Tetrahydrobiopterin, a cofactor for NOS, improves endothelial dysfunction during chronic alcohol consumption. Am J Physiol Heart Circ Physiol. 2001;281:H1863-1869.
• 12. Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1:a000034.
• 13. Sun SC. Non-canonical NF-κB signaling pathway. Cell Res. 2011;21:71-85.
• 14. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1:a001651.
• 15. Lim JW, Kim H, Kim KH. Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells. Lab Invest. 2001;81:349-360.
• 16. Arias-Salvatierra D, Silbergeld EK, Acosta-Saavedra LC, et al. Role of nitric oxide produced by iNOS through NF-κB pathway in migration of cerebellar granule neurons induced by Lipopolysaccharide. Cell Signal. 2011;23:425- 435.
• 17. Song Y, Wu X, Yang D, et al. Protective Effect of Andrographolide on Alleviating Chronic Alcoholic Liver Disease in Mice by Inhibiting Nuclear Factor Kappa B and Tumor Necrosis Factor Alpha Activation. J Med Food. 2020;23:409-415.
• 18. Nguyen TMT, Steane SE, Moritz KM, et al. Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure. J Physiol. 2019;597:5619-5637.
• 19. McCormack C, Hutchinson D, Burns L, et al. Prenatal Alcohol Consumption Between Conception a nd Recognition of Pregnancy. Alcohol Clin Exp Res. 2017;41:369-378.
• 20. Muggli E, O’Leary C, Donath S, et al. “Did you ever drink more?” A detailed description of pregnant women’s drinking patterns. BMC Public Health. 2016;16:683.
• 21. Bonthius DJ, West JR. Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure. Alcohol Clin Exp Res. 1990;14:107-18.
• 22. Doğanyiğit Z, Okan A, Kaymak E, et al. Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/ HMGB-1/ NF-κB pathway. Biomed Pharmacother. 2020;125:109967.
• 23. Inandiklioglu N, Doganyigit Z, Okan A, et al. Nephroprotective effect of Mapilarnil in lipopolysaccharide-induced sepsis through TLR4/NF-κB signaling pathway. Life Sci. 2021;284:119875.
• 24. Tsai JP, Lee CJ, Subeq YM, et al. Acute Alcohol Intoxication Exacerbate Rhabdomyolysis-Induced Acute Renal Failure in Rats. Int J Med Sci. 2017;14:680-689.
• 25. da Silva CBP, Ceron CS, Mendes AS, et al. Inducible nitric oxide synthase (iNOS) mediates ethanol-induced redox imbalance and upregulation of inflammatory cytokines in the kidney. Can J Physiol Pharmacol. 2021;99:1016-1025.
• 26. de Jesus Soares T, Costa RS, Balbi AP, et al. Inhibition of nuclear factor-kappa B activation reduces glycerol-induced renal injury. J Nephrol. 2006;19:439- 448.
• 27. Latchoumycandane C, Nagy LE, McIntyre TM. Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption. Free Radic Biol Med. 2015;86:179-190.
• 28. Gonzalez FJ. Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res. 2005;569:101-110.
• 29. Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med. 2008;44:723-738.
• 30. Lu Y, Cederbaum AI. CYP2E1 potentiation of LPS and TNFα-induced hepatotoxicity by mechanisms involving enhanced oxidative and nitrosative stress, activation of MAP kinases, and mitochondrial dysfunction. Genes Nutr. 2010;5:149-167.