Main Article Content
Abstract
Highlights:
- This study observed the histology of pancreatic β-cell damage without any intervention to the kidneys of the animal models.
- The histological analysis of the kidneys shows that STZ-induced animal models can be used for assessing kidney abnormalities due to hyperglycemia.
- A scoring system for the histological analysis was developed to evaluate the changes in the kidney cells.
Abstract
The kidneys are one of the organs affected by microvascular complications due to diabetes mellitus. Hyperglycemia plays an important role in glomerular, mesangial cell, and tubular damage in the kidneys. Metabolic dysregulation, including hyperglycemia, initiates cellular damage in the kidneys. Streptozotocin (STZ) is a chemical compound that is known to damage pancreatic cells and cause hyperglycemia. This study aimed to examine the effects of hyperglycemia on the morphology of the kidneys. Kidney tissues were observed histologically using a light microscope. Samples were taken from the kidneys of experimental animals administered with STZ to induce hyperglycemia. Observation was performed afterwards to investigate any damage to pancreatic cells. A total of 12 kidney samples were divided into two groups: the control group and the STZ-induced group. The samples were prepared before staining with hematoxylin-eosin and Masson's trichrome. The endothelium, podocytes, mesangial cells, and basement membrane of the glomerulus were examined. The tubules of the kidneys were also examined, and the presence or absence of connective tissue formation in both groups was statistically tested. The results suggested a significant difference in tubular damage (p<0.05) and an insignificant difference in an increase in the damage of other components of the kidneys (p>0.05) in the STZ-induced group. Significant morphological changes were observed in the hyperglycemic renal tubules due to the administration of STZ. In conclusion, STZ-induced hyperglycemia caused damage to the kidney components but overall had no significant impact on the kidney.
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References
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- Sundaram R, Nandhakumar E, Haseena Banu H (2019). Hesperidin, a citrus flavonoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Toxicology Mechanisms and Methods 29, 644–653. doi: 10.1080/1537 6516.2019.1646370
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References
Ameh OI, Okpechi IG, Agyemang C, et al (2019). Global, regional, and ethnic differences in diabetic nephropathy. In Diabetic Nephropathy, 33–44. Springer International Publishing, Cham. Available at: http://link.springer.com/10.1007/ 978-3-319-93521-8_3.
Amorim RG, Guedes G da S, Vasconcelos SM de L, et al (2019). Kidney disease in diabetes mellitus: Cross-linking between hyperglycemia, redox imbalance and inflammation. Arquivos Brasileiros de Cardiologia; doi: 10.5935/abc.20190077
Anders H-J, Huber TB, Isermann B, et al (2018). CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nature Reviews Nephrology 14, 361–377. doi: 10.1038/s41581-018-0001-y
Bayrasheva VK, Babenko AY, Dobronravov VA, et al (2016). Uninephrectomized high-fat-fed nicotinamide-streptozotocin-induced diabetic rats: A model for the investigation of diabetic nephropathy in type 2 Diabetes. Journal of Diabetes Research 2016, 1–18. doi: 10.1155/2016/8317850
Braga PC, Alves MG, Rodrigues AS, et al (2022). Mitochondrial pathophysiology on chronic kidney disease. Int J Mol Sci International Journal of Molecular Sciences 23, 1776. doi: 10.3390/ijms23031776
Cho NH, Shaw JE, Karuranga S, et al (2018). IDF diabetes atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Research and Clinical Practice 138, 271–281. doi: 10.1016/j.diabres.2018.02.023
Furman BL (2015). Streptozotocin"induced diabetic models in mice and rats. Current Protocols in Pharmacology 70. doi: 10.1002/0471141755.ph 0547s70
Giralt-López A, Molina-Van den Bosch M, Vergara A, et al (2020). Revisiting experimental models of diabetic nephropathy. International Journal of Molecular Sciences 21, 3587. doi: 10.3390/ijms2 1103587
Goyal SN, Reddy NM, Patil KR, et al (2016). Challenges and issues with streptozotocin-induced diabetes – A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chemico-Biological Interactions 244, 49–63. doi: 10.1016/j.cbi.2015.11.032
Inker LA, Tighiouart H, Coresh J, et al (2016). GFR estimation using β-Trace protein and β2-microglobulin in CKD. American Journal of Kidney Diseases 67, 40–48. doi: 10.1053/j.ajkd. 2015.07.025
Jusuf AA, Viventius Y, Djaali W (2021). Comparison between the effectiveness of manual acupuncture and laser acupuncture at EX-B3 weiwanxiashu in a rat model of type 2 diabetes. Journal of Acupuncture and Meridian Studies 14, 75–81. doi: 10.51507/j.jams.2021.14.2.75
Katsuda Y, Sasase T, Tadaki H, et al (2015). Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin. Experimental Animals 64, 161–9. doi: 10.1538/ expanim.14-0084
Khan NU, Lin J, Liu X, et al (2020). Insights into predicting diabetic nephropathy using urinary biomarkers. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1868, 140475. doi: 10.1016/j.bbapap.2020.140475
Kopp JB, Anders H-J, Susztak K, et al (2020). Podocytopathies. Nature Reviews Disease Primers 6, 68. doi: 10.1038/s41572-020-0196-7
Kymioni Vasiliki-Maria, Papamitsoy Theodora, Maggana Ioanna, et al (2016). TGF-b and diabetes mellitus. Journal of Pharmacy and Pharmacology 4. doi: 10.17265/2328-2150/2016.01.001
Levey AS, Inker LA, Coresh J (2014). GFR estimation: From physiology to public health. American Journal of Kidney Diseases 63, 820–834. doi: 10.1053/j.ajkd.2013.12.006
Lin JS, Susztak K (2016). Podocytes: the weakest link in diabetic kidney disease? Current Diabetes Reports 16, 45. doi: 10.1007/s11892-016-0735-5
de M. Bandeira S, da Fonseca L, da S. Guedes G, et al (2013). Oxidative stress as an underlying contributor in the development of chronic complications in diabetes mellitus. International Journal of Molecular Sciences 14, 3265–3284. doi: 10.3390/ijms14023265
Mondal SK (2017). Manual of histological techniques, illustrate. JP Medical Ltd.
Moonen L, D'Haese P, Vervaet B (2018). Epithelial cell cycle behaviour in the injured kidney. International Journal of Molecular Sciences 19, 2038. doi: 10.3390/ijms19072038
Nagata M (2016). Podocyte injury and its consequences. Kidney International 89, 1221–1230. doi: 10.1016/j.kint.2016.01.012
Pourghasem M, Shafi H, Babazadeh Z (2015). Histological changes of kidney in diabetic nephropathy. Caspian journal of internal medicine 6, 120–7. Available at: http://www.pubmed central.nih.gov/articlerender.fcgi?artid=PMC4650785
Reidy K, Kang HM, Hostetter T, et al (2014). Molecular mechanisms of diabetic kidney disease. Journal of Clinical Investigation 124, 2333–2340. doi: 10.1172/JCI72271
Rezk HM, El-Sherbiny M, Atef H, et al (2017). Effect of spironolactone on diabetic nephropathy in albino rats: ultrastructural and immunohistochemical study. International Journal of Scientific Reports 3, 110. doi: 10.18203/issn.24 54-2156.IntJSciRep20171997
Sameni HR, Ramhormozi P, Bandegi AR, et al (2016). Effects of ethanol extract of propolis on histopathological changes and anti"oxidant defense of kidney in a rat model for type 1 diabetes mellitus. Journal of Diabetes Investigation 7, 506–513. doi: 10.1111/jdi.12459
Soelistijo SA, Suastika K, Lindarto D, et al (2021). Pedoman pengelolaan dan pencegahan diabetes melitus tipe 2 di Indonesia 2021. PB PERKENI. Available at: https://pbperkeni.or.id/wp-content/uploads/2021/11/22-10-21-Website-Pedoman-Pengelolaan-dan-Pencegahan-DMT2-Ebook.pdf.
Sol M, Kamps JAAM, van den Born J, et al (2020). Glomerular endothelial cells as instigators of glomerular sclerotic diseases. Frontiers in Pharmacology 11. doi: 10.33 89/fphar.2020.5735 57.
Sundaram R, Nandhakumar E, Haseena Banu H (2019). Hesperidin, a citrus flavonoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Toxicology Mechanisms and Methods 29, 644–653. doi: 10.1080/1537 6516.2019.1646370
Sutariya B, Jhonsa D, Saraf MN (2016). TGF-β: the connecting link between nephropathy and fibrosis. Immunopharmacology and Immunotoxicology l 38, 39–49. doi: 10.3109/08923973.2015.1127382