Deneysel diyabet modelinde probiyotiklerin böbrek dokusuna etkisi

Yıl 2025, Cilt: 18 Sayı: 2, 340 - 355, 01.04.2025

Hülya Çetin , İlknur Lafci , Semih Tan , Bilgin Vural , Saim Özdamar

https://doi.org/10.31362/patd.1625516

Öz

Amaç: Diyabet, önemli bir halk sağlığı sorunu olan endokrin ve metabolik bir hastalıktır. Tüm dokularda olduğu gibi böbrek dokusunda da hasara yol açmaktadır. Probiyotiklerin yeterli miktarda kullanılması, hastalıkların önlenmesi ve tedavisinde faydalı olabileceği düşünülmektedir. Bu çalışmada, diyabetin böbrek dokusunda oluşturduğu hasara karşı probiyotik takviyesinin etkisini araştırmayı amaçladık.
Gereç ve yöntem: Toplam 34 sıçan beş gruba ayrıldı. Kontrol grubuna (K, n=5) PBS, yalnızca probiyotik alan gruba (Pm, n=5) ise probiyotik (0,6 mg/kg) uygulandı. Diyabet grubu (Dm, n=8) streptozotosin (50 mg/kg) ile diyabet oluşturuldu. PmD grubuna (n=8) diyabet oluşturulmadan önce probiyotik takviyesi uygulandı ve diyabet oluştuktan sonra da probiyotik uygulamasına devam edildi. DmP grubunda (n=8) ise önce diyabet oluşturuldu, ardından probiyotik takviyesi uygulandı. Böbrek dokuları histopatolojik ve immünohistokimyasal olarak incelendi; Bcl-2 ve alfa-SMA antikor ekspresyonları değerlendirildi.
Bulgular: Kontrol grubunda histopatolojik değişiklikler gözlenmezken, Dm grubunda orta-hafif nefrotoksisite saptandı. Probiyotik takviyesi alan diyabet gruplarında ise hafif nefrotoksisite gözlendi. Dm grubunda Bcl-2 ekspresyonu azalmış olup, DmP ve PmD gruplarında ise daha yüksek seviyelerde olduğu tespit edilmiştir. Alfa-SMA ekspresyonu ise Dm grubunda artarken, DmP ve PmD gruplarında daha düşük seviyelerde olduğu gözlenmiştir.
Sonuç: Histopatolojik ve immünohistokimyasal değerlendirmeler, probiyotiklerin diyabetin neden olduğu böbrek hasarına karşı koruyucu bir etki gösterdiğini ortaya koymaktadır.

Anahtar Kelimeler

Diyabet, probiyotik, böbrek, alfa-SMA, Bcl-2

Etik Beyan

Çalışma için gerekli izin, Pamukkale Üniversitesi Hayvan Deneyleri Etik Kurulu’nun PAÜHDEK-2021/37 sayılı kararı ile alındı.

Destekleyen Kurum

Bu çalışma Pamukkale Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir (BAP Proje no: 2021SABE018)

Proje Numarası

2021SABE018

Teşekkür

Pamukkale Üniversitesi Deney Hayvanları Araştırma Birimine (DEHAB) deney süresince verdikleri katkıdan dolayı teşekkür ederiz

Effect of probiotics on kidney tissue in an experimental diabetes model

Öz

Purpose: Diabetes, a major public health issue, is an endocrine and metabolic disease that causes damage to various tissues, including the kidneys. Probiotics are thought to play a beneficial role in the prevention and treatment of diseases when used in sufficient amounts. This study aims to investigate the effects of probiotic supplementation on kidney tissue damage induced by diabetes.
Materials and methods: A total of 34 rats were divided into five groups. The control group (K, n=5) received PBS, while the probiotic-only group (Pm, n=5) was given probiotics (0.6 mg/kg). In the diabetes group (Dm, n=8), diabetes was induced using streptozotocin (50 mg/kg). The PmD group (n=8) received probiotic supplementation before diabetes induction, and probiotic administration continued after diabetes was induced. In contrast, the DmP group (n=8) first underwent diabetes induction, followed by probiotic supplementation. Kidney tissues were examined histopathologically and immunohistochemically, with Bcl-2 and alpha-SMA antibody expressions evaluated.
Results: No histopathological alterations were observed in the control group. In the Dm group, moderate-to-mild nephrotoxicity was detected, while the probiotic-supplemented diabetes groups exhibited mild nephrotoxicity. Bcl-2 expression was decreased in the Dm group but was found to be higher in the DmP and PmD groups. Conversely, alpha-SMA expression was elevated in the Dm group, whereas it was lower in the DmP and PmD groups.
Conclusion: Histopathological and immunohistochemical analyses indicate that probiotics exert a protective effect against diabetes-induced kidney damage.

Anahtar Kelimeler

Diabetes, probiotic, kidney, alpha-SMA, Bcl-2

Etik Beyan

Permission for the study was obtained from Pamukkale University Animal Experiments Ethics Committee with the decision numbered and dated PAUHDEK-2021/37.

Destekleyen Kurum

This study was supported by Pamukkale University Scientific Research Projects Coordination Office (BAP Project no: 2021SABE018)

Proje Numarası

2021SABE018

Teşekkür

We would like to thank Pamukkale University Experimental Animal Research Unit (DEHAB) for their contribution during the experiment.

Kaynakça

• American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36 Suppl 1(Suppl 1):S67-S74. doi:10.2337/dc13-S067
• World Health Organization Available at: https://www.who.int/data/gho/publications/world-health-statistics. Accessed 25.06.2024
• Me TA. Hastalıklarda beslenme tedavisi. İstanbul: Hatipoğlu Matbaacılık; 2013;1:277-304.
• Kanchan G, Dagle P, Pushpalata C, Joshi Y, Kadam V. A review on some nephroprotective medicinal plants. International Journal of Pharmaceutical Sciences and Research. 2012;2012(8):2451. doi:10.13040/ijpsr.0975-8232.3(8).2451-54
• Lu L, Zhong Z, Gu J, Nan K, Zhu M, Miao C. ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy. Mol Med. 2021;27(1):74. Published 2021 Jul 8. doi:10.1186/s10020-021-00339-7
• American Diabetes Association. Diabetes and employment. Diabetes Care. 2009;32 Suppl 1(Suppl 1):S80-S84. doi:10.2337/dc09-S080
• Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1989;32(3):151-159. doi:10.1007/BF00265086
• Azpiroz F, Malagelada C. Diabetic neuropathy in the gut: pathogenesis and diagnosis. Diabetologia. 2016;59(3):404-408. doi:10.1007/s00125-015-3831-1
• Wu SL. Staging of type 2 diabetes mellitus. Genet Mol Res. 2015;14(1):2118-2121. Published 2015 Mar 20. doi:10.4238/2015.March.20.22
• Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55-60. doi:10.1038/nature11450
• Kobyliak N, Conte C, Cammarota G, et al. Probiotics in prevention and treatment of obesity: a critical view. Nutr Metab (Lond). 2016;13:14. Published 2016 Feb 20. doi:10.1186/s12986-016-0067-0
• Gilbert RE, Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury?. Kidney Int. 1999;56(5):1627-1637. doi:10.1046/j.1523-1755.1999.00721.x
• Shi R, Ye J, Fan H, et al. Lactobacillus plantarum LLY-606 supplementation ameliorates hyperuricemia via modulating intestinal homeostasis and relieving inflammation. Food Funct. 2023;14(12):5663-5677. Published 2023 Jun 19. doi:10.1039/d2fo03411e
• Sang LX, Chang B, Wang BY, Liu WX, Jiang M. Live and heat-killed probiotic: effects on chronic experimental colitis induced by dextran sulfate sodium (DSS) in rats. Int J Clin Exp Med. 2015;8(11):20072-20078. Published 2015 Nov 15.
• Al Shabanah OA, Aleisa AM, Al Yahya AA, et al. Increased urinary losses of carnitine and decreased intramitochondrial coenzyme A in gentamicin-induced acute renal failure in rats. Nephrol Dial Transplant. 2010;25(1):69-76. doi:10.1093/ndt/gfp457
• Ruan Y, Sun J, He J, Chen F, Chen R, Chen H. Effect of Probiotics on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. PLoS One. 2015;10(7):e0132121. Published 2015 Jul 10. doi:10.1371/journal.pone.0132121
• Kamarlı H. Pre- Probiyotikler ve Diyabet. Bes Diy Derg [Internet]. 2019;47:92-101. Erişim adresi: https://beslenmevediyetdergisi.org/index.php/bdd/article/view/1320. Erişim tarihi 22 Ocak 2025
• Cai X, Wang L, Wang X, Liu S. Effect of high dietary fiber low glycemic index diet on intestinal flora, blood glucose and inflammatory response in T2DM patients. Biomed. Res. 2017;28:9371-9375.
• Li X, Wang N, Yin B, et al. Effects of Lactobacillus plantarum CCFM0236 on hyperglycaemia and insulin resistance in high-fat and streptozotocin-induced type 2 diabetic mice. J Appl Microbiol. 2016;121(6):1727-1736. doi:10.1111/jam.13276
• Yun SI, Park HO, Kang JH. Effect of Lactobacillus gasseri BNR17 on blood glucose levels and body weight in a mouse model of type 2 diabetes. J Appl Microbiol. 2009;107(5):1681-1686. doi:10.1111/j.1365-2672.2009.04350.x
• Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D. Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb Pathog. 2012;53(2):100-108. doi:10.1016/j.micpath.2012.05.007
• Jones RB, Alderete TL, Martin AA, et al. Probiotic supplementation increases obesity with no detectable effects on liver fat or gut microbiota in obese Hispanic adolescents: a 16-week, randomized, placebo-controlled trial. Pediatr Obes. 2018;13(11):705-714. doi:10.1111/ijpo.12273
• Sudha MR, Ahire JJ, Jayanthi N, Tripathi A, Nanal S. Effect of multi-strain probiotic (UB0316) in weight management in overweight/obese adults: a 12-week double blind, randomised, placebo-controlled study. Benef Microbes. 2019;10(8):855-866. doi:10.3920/BM2019.0052
• Lu L, Zhong Z, Gu J, Nan K, Zhu M, Miao C. ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy. Mol Med. 2021;27(1):74. Published 2021 Jul 8. doi:10.1186/s10020-021-00339-7
• Sengul E, Gelen SU, Yıldırım S, Çelebi F, Çınar A. Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats. Asian Pacific Journal of Tropical Biomedicine. 2019;9(3):116-122.
• Miraghajani M, Zaghian N, Mirlohi M, Feizi A, Ghiasvand R. The Impact of Probiotic Soy Milk Consumption on Oxidative Stress Among Type 2 Diabetic Kidney Disease Patients: A Randomized Controlled Clinical Trial. J Ren Nutr. 2017;27(5):317-324. doi:10.1053/j.jrn.2017.04.004
• Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition. 2012;28(5):539-543. doi:10.1016/j.nut.2011.08.013
• Ostadrahimi A, Taghizadeh A, Mobasseri M, et al. Effect of probiotic fermented milk (kefir) on glycemic control and lipid profile in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Iran J Public Health. 2015;44(2):228-237.
• Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Kyriienko D, Komissarenko I. Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial. Diabetes Metab Syndr. 2018;12(5):617-624. doi:10.1016/j.dsx.2018.04.015
• Razmpoosh E, Javadi A, Ejtahed HS, Mirmiran P, Javadi M, Yousefinejad A. The effect of probiotic supplementation on glycemic control and lipid profile in patients with type 2 diabetes: A randomized placebo controlled trial. Diabetes Metab Syndr. 2019;13(1):175-182. doi:10.1016/j.dsx.2018.08.008
• Wang Y, Dilidaxi D, Wu Y, Sailike J, Sun X, Nabi XH. Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice. Biomed Pharmacother. 2020;125:109914. doi:10.1016/j.biopha.2020.109914
• Khalil NA, Eltahan NR, Elaktash HM, Aly S, Sarbini SR. Prospective evaluation of probiotic and prebiotic supplementation on diabetic health associated with gut microbiota. Food Bioscience. 2021;42:101149.
• Glastras SJ, Chen H, Teh R, et al. Mouse Models of Diabetes, Obesity and Related Kidney Disease. PLoS One. 2016;11(8):e0162131. Published 2016 Aug 31. doi:10.1371/journal.pone.0162131
• Negm El Dein A, Ezzat A, Aly HF, Awad G, Farid M. Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats. Nutr Res. 2022;108:22-32. doi:10.1016/j.nutres.2022.10.003
• Punaro GR, Maciel FR, Rodrigues AM, et al. Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress. Nitric Oxide. 2014;37:53-60. doi:10.1016/j.niox.2013.12.012
• Gilbert RE, Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury?. Kidney Int. 1999;56(5):1627-1637. doi:10.1046/j.1523-1755.1999.00721.x
• Vardı N, Iraz M, Öztürk F, Uçar M, Gül M, Eşrefoğlu M, Otlu A. Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri. J Turgut Ozal Med Cent. Haziran 2005;12(3):145-152.
• Kikuchi Y, Nonoguchi H, Machida K, Wakamatsu S, Koga H, Tomita K. Regulation of the apoptosis‐related genes, Bax and Bcl‐2, in the early stage of diabetes mellitus. Nephrology. 2002;7(6):294-302.
• Li A, Yi B, Han H, et al. Vitamin D-VDR (vitamin D receptor) regulates defective autophagy in renal tubular epithelial cell in streptozotocin-induced diabetic mice via the AMPK pathway. Autophagy. 2022;18(4):877-890. doi:10.1080/15548627.2021.1962681
• Manaer T, Yu L, Nabi XH, Dilidaxi D, Liu L, Sailike J. The beneficial effects of the composite probiotics from camel milk on glucose and lipid metabolism, liver and renal function and gut microbiota in db/db mice. BMC Complement Med Ther. 2021;21(1):127. Published 2021 Apr 22. doi:10.1186/s12906-021-03303-4
• García Arroyo FE, Gonzaga G, Muñoz Jiménez I, et al. Probiotic supplements prevented oxonic acid-induced hyperuricemia and renal damage. PLoS One. 2018;13(8):e0202901. Published 2018 Aug 24. doi:10.1371/journal.pone.020290