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DOI :10.26650/IUITFD.2021.849531   IUP :10.26650/IUITFD.2021.849531    Tam Metin (PDF)

VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI

İlknur Bingül, Canan Küçükgergin, Abdurrahman Fatih Aydın, Asiye Işın Doğan Ekici, Semra Doğru Abbasoğlu, Mehmet Müjdat Uysal

Amaç: Vitamin D antioksidan, antiinflamatuvar ve antiglikasyon etkinliğe ve karaciğeri koruyucu potansiyele sahiptir. Vitamin D eksikliği/yetersizliği (VDD/VDI) ile karaciğer bozukluklarının ciddiyeti arasında bir ilişki bulunmaktadır. VDD’nin alkole bağlı olmayan yağlı karaciğer hastalığının (NAFLD) progresyonunda etkili olduğu bildirilmiştir. Fakat deneysel sonuçlar yeterli değildir. Bu nedenle, bu çalışmada VDD’nin yüksek fruktozlu (HFr) içme suyu uygulanarak oluşturulan NAFLD üzerine etkisi incelendi. Gereç ve Yöntemler: Erkek Wistar sıçanlar kontrol, HFr, VDD+Fr ve VDD olmak üzere 4 gruba ayrıldı. Kontrol ve HFr grupları Vit D3 içeren, diğerleri ise Vit D3 içermeyen yemle 12 hafta beslendiler. HFr (%30; w/v) içme suyu ile son 8 hafta uygulandı. İnsulin direnci (IR), serum lipitleri, hepatik trigliserit, lipit peroksit, protein karbonil, ileri glikasyon ürünleri (AGEs) ve inflamasyon (TNF-α ve miyeloperoksidaz) göstergeleri tayin edildi. Bulgular: HFR ve VDD+HFr gruplarında serumda transaminazlar arttı, hipertrigliseridemi, ve insülin direnci oluştu. Her iki grupta da karaciğerde trigliserit düzeyleri, lipit ve protein oksidasyon ürünleri, protein glikasyon ve inflamasyon göstergeleri arttı, mikroveziküler steatoz ve hepatosit balonlaşması saptandı. IR ve inflamasyon göstergeleri VDD+HFr grubunda daha yüksek olmasına rağmen, iki grup arasında serum transaminazları, karaciğer trigliserit, lipit ve protein oksidasyon ürünleri ve glikasyon göstergeleri düzeylerinde bir farklılık bulunmadı. Ancak Nrf2 mRNA ekspresyonu ile süperoksit dismutaz ve glutatyon peroksidazın mRNA ekspresyonları ve aktivitelerinin VDD+HFr grubunda daha yüksek olduğu bulundu. Sonuç: Sonuçlarımız VDD’nin HFr ile oluşturulan karaciğer hasarı ve glikooksidatif streste bir değişiklik oluşturmadığını göstermektedir.

Anahtar Kelimeler: Vitamin D yetersizliği, yüksek fruktozlu diyet, alkolik olmayan karaciğer hastalığı, glikooksidatif stres, anti oksidanlar, inflamasyon
DOI :10.26650/IUITFD.2021.849531   IUP :10.26650/IUITFD.2021.849531    Tam Metin (PDF)

VITAMIN D DEFICIENCY DID NOT AUGMENT THE PROGRESSION OF HIGH-FRUCTOSE-INDUCED NONALCOHOLIC FATTY LIVER DISEASE IN RATS

İlknur Bingül, Canan Küçükgergin, Abdurrahman Fatih Aydın, Asiye Işın Doğan Ekici, Semra Doğru Abbasoğlu, Mehmet Müjdat Uysal

Objective: Vitamin D has antioxidant, anti-inflammatory and antiglycation activities, and hepatoprotective potential. There is a relationship between vitamin D deficiency (VDD) and the severity of liver disorders. VDD has been proposed to contribute to the progression of nonalcoholic fatty liver disease (NAFLD). However, experimental results are not clear. Therefore, in this study, the effects of a VDD diet on high fructose (HFr) drinking-induced NAFLD was evaluated. Material and Method: Male Wistar rats were divided into four groups as control, HFr, VDD+HFr, and VDD. Control and HFr groups were fed a control diet, and other groups with a VDD-diet for 12 weeks. HFr (30%; w/v; in drinking water) was given in the last 8 weeks. Insulin resistance (IR), serum lipids, hepatic triglyceride, lipid peroxide, protein carbonyl, advanced glycation end products (AGEs) and inflammation (TNF-α and myeloperoxidase) parameters, and histopathological changes were investigated. Results: Increases in serum transaminases, hypertriglyceridemia, and IR were observed in HFr and VDD+HFr groups. Increased liver triglyceride, lipid and protein oxidation products, protein glycation and inflammation markers as well as microvesicular hepatic steatosis and hepatocyte ballooning were observed in both groups. Although IR and hepatic inflammation markers were higher in the VDD+HFr group, serum transaminases, hepatic triglyceride, lipid and protein oxidation products, and glycation indicators in the liver did not alter between the two groups. However, Nrf2 mRNA expression and superoxide dismutase and glutathione peroxidase mRNA expression and activities were significantly higher in the VDD+HFr group. Conclusion: Our results show that VDD did not augmented HFr-induced hepatotoxicity and glycooxidative stress in the liver of rats.

Anahtar Kelimeler: Vitamin D deficiency, high fructose diet, nonalcoholic liver disease, glycooxidative stress, antioxidant, inflammation

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Referanslar

  • 1. Ibrahim MA, Kelleni M, Geddawy A. Nonalcoholic fatty liver disease: Current and potential therapies. Life Sci 2013;92(2):114-8. [CrossRef] google scholar
  • 2. Fernando DH, Forbe JM, Angus PW, Herath CB. Development and progression of non-alcoholic fatty liver disease: The role of advanced glycation end products. Int J Mol Sci 2019;20(20):5037. [CrossRef] google scholar
  • 3. Alwahsh SM, Gebhardt R. Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD). Arch Toxicol 2017;91(4):1545-63. [CrossRef] google scholar
  • 4. Takahashi Y, Soejima Y, Fukusato T. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 2012;18(19):2300-8. [CrossRef] google scholar
  • 5. Jegatheesan P, De Bandt JP. Fructose and NAFLD: Multifaceted aspects of fructose metabolism. Nutrients 2017;9(3):230. [CrossRef] google scholar
  • 6. Gugliucci A. Formation of fructose-mediated advanced glycation end products and their roles in metabolic and inflammatory diseases. Adv Nutr 2017;8(1):54-62. [CrossRef] google scholar
  • 7. Kwok RM, Torres DM, Harrison SA. Vitamin D and nonalcoholic fatty liver disease (NAFLD): Is it more than just an association? Hepatology 2013;58(3):1166-74. [CrossRef] google scholar
  • 8. Uberti F, Morsanuto V, Molinari C. Vitamin D in oxidative stress and diseases. ‘A Critical Evaluation of Vitamin D-Basic Overview. Ed: Sivakumar Joghi Thatha Gowder, IntechOpen, Chapter 2, pp 47-73. 2017. [CrossRef] google scholar
  • 9. Kheirouri S, Alizadeh M. Vitamin D and advanced glycation end products and their reseptors. Pharmacol Res 2020;158:104879. [CrossRef] google scholar
  • 10. Khan S, Ali A, Khan S, Bakillah A, Damanhouri G, Khan A, et al. Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D. Nutr Metab 2018;15:13. [CrossRef] google scholar
  • 11. Eliades M, Spyrou E. Vitamin D: A new player in non-alcoholic fatty liver disease? World J Gastroenterol 2015;21(6):1718-27. [CrossRef] google scholar
  • 12. Berridge MJ. Vitamin D signalling in health and disease. Biochem Biophys Res Commun 2015;460(1):53-71. [CrossRef] google scholar
  • 13. Wang H, Chen W, Li D, Yin X, Zhang X, Olsen N, et al. Vitamin D and chronic diseases. Aging Dis 2017;8(3):346-53. [CrossRef] google scholar
  • 14. Wimalawansa SJ. Vitamin D deficiency: Effects on oxidative stress, epigenetics, gene regulation and aging. Biology 2019;8(2):30-45. [CrossRef] google scholar
  • 15. Institute of Medicine. Dietary references intakes for calcium and vitamin D. Eds: Ross AC, Taylor CL, Yaktine AL, Del Valle HB, Washington-DC, National Academies Press (US), 2011. google scholar
  • 16. Elangovan H, Chahal S, Gunton JE. Vitamin D in liver disease: Current evidence and potential directions. Biochim Biophys Acta 2017;1863(4):907-16. [CrossRef] google scholar
  • 17. Karatayli E, Stokes CS, Lammert F. Vitamin D in preclinical models of fatty liver disease. Anticancer Res 2020;40(1): 527-34. [CrossRef] google scholar
  • 18. Rachmilewitz D, Stamler JS, Karmeli F, Mullins ME, Singel DJ, Loscalzo J, et al. “Peroxynitrite-induced rat colitis - a new model of colonic inflammation”. Gastroenterology 1993;105(6):1681-8. [CrossRef] google scholar
  • 19. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 1999;27(5-6):612-6. [CrossRef] google scholar
  • 20. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10. [CrossRef] google scholar
  • 21. Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994;233:357-63. [CrossRef] google scholar
  • 22. Hanasand M, Omdal R, Norheim KB, G0ransson LG, Brede C, Johnson G. Improved detection of advanced oxidation protein products in plasma. Clin Chim Acta 2012;413(9-10):901-6. [CrossRef] google scholar
  • 23. Münch G, Keis R, Wessels A, Riederer P, Bahner U, Heidland A, et al. Determination of advanced glycation end products in serum by fluorescence spectroscopy and competitive ELISA. Eur J Clin Chem Clin Biochem 1997;35(9):669-77. [CrossRef] google scholar
  • 24. Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’’: the FRAP assay. Anal Biochem 1996;239(1):70-6. [CrossRef] google scholar
  • 25. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8. google scholar
  • 26. Mylorie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986;82(3):512-20. [CrossRef] google scholar
  • 27. Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium deficient rat liver. Biochem Biophys Res Commun 1976;425(3):503-9. [CrossRef] google scholar
  • 28. Worthington V. Catalase. In: Worthington Enzyme Manuel: Enzymes and related biochemicals. New Jersey: Worthington Biochemical Corporation, pp.77-80, 1993. google scholar
  • 29. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, et al. Measurement of protein using bicinchoninic acid. Anal Biochem 1985;150(1):76-85. [CrossRef] google scholar
  • 30. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol 2007;47(4):598-607. [CrossRef] google scholar
  • 31. Bingül I, Aydın AF, Başaran-Küçükgergin C, Doğan-Ekici I, Çoban J, Doğru-Abbasoğlu S, et al. High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats. Int Immunopharmacol 2016;39:199-207. [CrossRef] google scholar
  • 32. Bagul PK, Middela H, Matapally S, Padiya R, Bastia T, Madhusudana K, et al. Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats. Pharmacol Res 2012:66(3):260-8. [CrossRef] google scholar
  • 33. Giriş M, Doğru-Abbasoğlu S, Kumral A, Olgaç V, Koçak-Toker N, Uysal M. Effect of carnosine alone or combined with a-tocopherol on hepatic steatosis and oxidative stress in fructose-induced insulin-resistant rats. J Physiol Biochem 2014;70(2):385-95. [CrossRef] google scholar
  • 34. Li W, Lu, Y. Hepatoprotective effects of sophoricoside against fructose-induced liver injury via regulating lipid metabolism, oxidation, and inflammation in mice. J Food Sci 2018;83(2):552-8. [CrossRef] google scholar
  • 35. Yang Y, Wang J, Zhang Y, Li J, Sun W. Black sesame seeds ethanol extract ameliorates hepatic lipid accumulation, oxidative stress, and insulin resistance in fructose-induced nonalcoholic fatty liver disease. J Agric Food Chem 2018;66(40):10458-69. [CrossRef] google scholar
  • 36. Pai SA, Munshi RP, Panchal FH, Gaur IS, Juvekar AR. Chrysin ameliorates nonalcoholic fatty liver disease in rats. Naunyn-Schmiedeberg’s Arch Pharmacol 2019;392(12):1617-28. [CrossRef] google scholar
  • 37. Capeillere-Blandin C, Gausson V, Descamps -Latscha B, Witko-Sarsat V. Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim Biophys Acta 2004;1689(2):91-102. [CrossRef] google scholar
  • 38. Mokhtari Z, Hekmatdoost A, Nourian M. Antioxidant efficacy of vitamin D. J Parathyroid Dis 2017;5(1):11-6. google scholar
  • 39. Zhu CG, Liu YX, Wang H, Wang BP, Qu HQ, Wang BL, et al. Active form of vitamin D ameliorates non-alcoholic fatty liver disease by alleviating oxidative stress in a high-fat diet rat model. Endocr J 2017;64(7):663-73. [CrossRef] google scholar
  • 40. Liu Y, Wang M, Xu W, Zhang H, Qian W, Li X, et al. Active vitamin D supplementation alleviates and progression of non-alcoholic liver disease by repressing the p53 pathway. Life Sci 2020;241:117086. [CrossRef] google scholar
  • 41. Ma M, Long Q, Chen F, Zhang T, Wang W. Active vitamin D impedes the progression of non-alcoholic cell senescence in a rat model. Clin Res Hepatol Gastroenterol 2020;44(4):513-23. [CrossRef] google scholar
  • 42. Kong M, Zhu L, Bai L, Zhang X, Chen Y, Liu S, et al. Vitamin D deficiency promotes nonalcoholic steatohepatitis through impaired enterohepatic circulation in animal model. Am J Physiol Gastrointest Liver Physiol 2014;307(9):G883-G893. [CrossRef] google scholar
  • 43. Su D, Nie Y, Zhu A, Chen Z, Wu P, Zhang L. et al. Vitamin D signaling through induction of paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models. Front Physiol 2016;7:498. [CrossRef] google scholar
  • 44. Roth CL, Elfers CT, Figlewicz DP, Melhorn SJ, Morton GJ, Hoofnagle A, et al. Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and Toll-like receptor activation. Hepatology 2012;55(4):1103-11. [CrossRef] google scholar
  • 45. Li W, Zhang L, Liu Y, Wang C, Long Y, Huang Z, et al. Metabolite profiling of mice under long-term fructose drinking and vitamin D deficiency: increased risks for metabolic syndrome and nonalcoholic fatty liver disease. J Physiol Biochem 2020;76(4):587-98. [CrossRef] google scholar
  • 46. Liu XJ, Wang BW, Zhang C, Xia MZ, Chen YH, Hu CQ, et al. Vitamin D deficiency attenuates high-fat diet-induced hyperinsulinemia and hepatic lipid accumulation in male mice. Endocrinology 2015;156(6):2103-13. [CrossRef] google scholar
  • 47. Maia-Ceciliano TC, Dutra RR, Aguila MB, Mandarim-De-Lacerda CA. The deficiency and the supplementation of vitamin D and liver: Lessons of chronic fructose-rich diet in mice. J Steroid Biochem Mol Biol 2019;192:105399. [CrossRef] google scholar
  • 48. Mallya SM, Corrado KR, Saria EA, Yuan FNF, Tran HQ, Saucier K, et al. Modeling vitamin D deficiency and moderate deficiency in adult mice via dietary cholecalciferol restriction. Endocrin Res 2016;41(4):290-9. [CrossRef] google scholar
  • 49. Bhat M, Ismail A. Vitamin D treatment protects against and reverses oxidative stress induced muscle proteolysis. J Steroid Biochem Mol Biol 2015;152:171-9. [CrossRef] google scholar
  • 50. Tao S, Yuan Q, Mao L, Chen FL, Ji F, Cui ZH. Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes. Oncotarget 2017;8(40):67605-13. [CrossRef] google scholar

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APA

Bingül, İ., Küçükgergin, C., Aydın, A.F., Doğan Ekici, A.I., Doğru Abbasoğlu, S., & Uysal, M.M. (2021). VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI. İstanbul Tıp Fakültesi Dergisi, 84(3), 360-368. https://doi.org/10.26650/IUITFD.2021.849531


AMA

Bingül İ, Küçükgergin C, Aydın A F, Doğan Ekici A I, Doğru Abbasoğlu S, Uysal M M. VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI. İstanbul Tıp Fakültesi Dergisi. 2021;84(3):360-368. https://doi.org/10.26650/IUITFD.2021.849531


ABNT

Bingül, İ.; Küçükgergin, C.; Aydın, A.F.; Doğan Ekici, A.I.; Doğru Abbasoğlu, S.; Uysal, M.M. VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI. İstanbul Tıp Fakültesi Dergisi, [Publisher Location], v. 84, n. 3, p. 360-368, 2021.


Chicago: Author-Date Style

Bingül, İlknur, and Canan Küçükgergin and Abdurrahman Fatih Aydın and Asiye Işın Doğan Ekici and Semra Doğru Abbasoğlu and Mehmet Müjdat Uysal. 2021. “VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI.” İstanbul Tıp Fakültesi Dergisi 84, no. 3: 360-368. https://doi.org/10.26650/IUITFD.2021.849531


Chicago: Humanities Style

Bingül, İlknur, and Canan Küçükgergin and Abdurrahman Fatih Aydın and Asiye Işın Doğan Ekici and Semra Doğru Abbasoğlu and Mehmet Müjdat Uysal. “VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI.” İstanbul Tıp Fakültesi Dergisi 84, no. 3 (Nov. 2024): 360-368. https://doi.org/10.26650/IUITFD.2021.849531


Harvard: Australian Style

Bingül, İ & Küçükgergin, C & Aydın, AF & Doğan Ekici, AI & Doğru Abbasoğlu, S & Uysal, MM 2021, 'VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI', İstanbul Tıp Fakültesi Dergisi, vol. 84, no. 3, pp. 360-368, viewed 23 Nov. 2024, https://doi.org/10.26650/IUITFD.2021.849531


Harvard: Author-Date Style

Bingül, İ. and Küçükgergin, C. and Aydın, A.F. and Doğan Ekici, A.I. and Doğru Abbasoğlu, S. and Uysal, M.M. (2021) ‘VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI’, İstanbul Tıp Fakültesi Dergisi, 84(3), pp. 360-368. https://doi.org/10.26650/IUITFD.2021.849531 (23 Nov. 2024).


MLA

Bingül, İlknur, and Canan Küçükgergin and Abdurrahman Fatih Aydın and Asiye Işın Doğan Ekici and Semra Doğru Abbasoğlu and Mehmet Müjdat Uysal. “VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI.” İstanbul Tıp Fakültesi Dergisi, vol. 84, no. 3, 2021, pp. 360-368. [Database Container], https://doi.org/10.26650/IUITFD.2021.849531


Vancouver

Bingül İ, Küçükgergin C, Aydın AF, Doğan Ekici AI, Doğru Abbasoğlu S, Uysal MM. VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI. İstanbul Tıp Fakültesi Dergisi [Internet]. 23 Nov. 2024 [cited 23 Nov. 2024];84(3):360-368. Available from: https://doi.org/10.26650/IUITFD.2021.849531 doi: 10.26650/IUITFD.2021.849531


ISNAD

Bingül, İlknur - Küçükgergin, Canan - Aydın, AbdurrahmanFatih - Doğan Ekici, AsiyeIşın - Doğru Abbasoğlu, Semra - Uysal, MehmetMüjdat. “VİTAMİN D EKSİKLİĞİ SIÇANLARDA ALKOLE BAĞLI OLMAYAN YAĞLI KARACİĞER HASTALIĞININ PROGRESYONUNU ARTTIRMADI”. İstanbul Tıp Fakültesi Dergisi 84/3 (Nov. 2024): 360-368. https://doi.org/10.26650/IUITFD.2021.849531



ZAMAN ÇİZELGESİ


Gönderim29.12.2020
Kabul16.04.2021
Çevrimiçi Yayınlanma14.07.2021

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