Comparison of the Pathological Picture of Experimental Diabetic Nephropathy in Rats at Early (1 month) and Late (8 months) Stages

A. Yu. Zharikov, S.O. Filinova, O. N. Mazko, O. G. Makarova, Yu. V. Korenovsky, A. V. Lepilov, I. P. Bobrov, O. V. Azarova

 
International Journal of Biomedicine. 2019;9(4):345-349.
DOI: 10.21103/Article9(4)_OA14
Originally published December 15, 2019

Abstract: 

The research objective was to investigate the pathological picture of diabetic nephropathy (DN) in the 8-month streptozotocin (STZ)-induced diabetes mellitus (DM) and compare it with the previously obtained picture of DN in the 1-month STZ-induced DM.
Materials and methods:Experiments were conducted on 15 male Wistar rats aged 2-3 months and weighing 250–280g. To induce DM, the animals were injected intraperitoneally 1ml of STZ solution in the citrate buffer at a dose of 65mg/kg. In accordance with modern ideas about the peculiarities of DM modeling using STZ for more selective modeling of type 2 DM, the rats were previously injected with an intraperitoneal solution of cytoflavin based on a nicotinamide dose of 115mg/kg. After 8 months of the experiment, the concentration of glucose, protein, and creatinine was determined in urine. The animals were euthanized under ethereal anesthesia and both kidneys were extracted, cleaned and washed with a physiological solution. In the renal tissues of animals, we determined the concentration of thiobarbituric acid reactive products, total pro-oxidant activity, total antioxidant activity, activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase).  With the help of a morphometric method of research, the area of renal glomeruli and the area of capillary lumens were measured, and after a special computer processing of digital photos, the total area of the vascular bed in the glomerulus and the area of mesangium in the renal glomerulus were assessed.
Results: DN in the 8-month STZ-induced DM was more pronounced than with the 1-month STZ-induced DM. The revealed biochemical and morphological signs of the 8-month STZ-induced DM indicate the irreversible nature of its course and the impossibility of its pharmacological correction.

Keywords: 
diabetes mellitus • streptozotocin • diabetic nephropathy
References: 
  1. Iminger-Finger I, Kargul J, Laurent GJ. Diabetes: Present and future. Int J Biochem Cell Biol. 2017 Jul;88:196. doi: 10.1016/j.biocel.2017.06.003.
  2. Fouli GE, Gnudi L. The Future: Experimental Therapies for Renal Disease in Diabetes. Nephron. 2019;143(1):3-7. doi: 10.1159/000492825.
  3. Zharikov AYu, Shchekochikhina RO. [Diabetic Nephropaty. Modern View of The Problem]. Bulletin of Medical Science. 2018; 2(10): 22-28. [Article in Russian].
  4. Van JA, Scholey JW, Konvalinka A. Insights into Diabetic Kidney Disease Using Urinary Proteomics and Bioinformatics. J Am Soc Nephrol. 2017;28(4):1050-1061 doi: 10.1681/ASN.2016091018.
  5. Kiliś-Pstrusińska K. [Carnosine, carnosinase and kidney diseases]. Postepy Hig Med Dosw (Online) 2012; 66:215-21. [Article in Polish].
  6. Peters V, Klessens CQ, Baelde HJ, Singler B, Veraar KA, Zutinic A, et al. Intrinsic carnosine metabolism in the human kidney. Amino Acids. 2015;47(12):2541-50. doi: 10.1007/s00726-015-2045-7.
  7. Filinova SO, Zharikov AY, Bobrov IP, Mazko ON, Makarova OG. [Pathomorphological picture of diabetic nephropathy in experimental diabetes mellitus]. Kazan Medical Journal 2019; 100(1): 147-152.[Article in Russian].
  8. Zharikov AYu, Balandovich BA, Shchekochikhina RO, Zharikova GV. Kidney function in experimental diabetes. Nephrology. 2019; 23(1): 79-83.
  9. Spasov AA, Vorohkova MP, Snegur GL, Cheplyaeva NI, Chepurnova MV. [Experimental model of a type 2 diabetes]. Biomedicine 2011;(3):12-18. [Article in Russian].
  10. Bryukhanov VM, Zverev YaF, Lampatov VV, Zharikov AYu, Talalayeva OS. Methods of preclinical (experimental) research of the effect of medicines on renal function. Novosibirsk: Geo; 2013. [In Russian].
  11. Fiorina P, Vergani A, Bassi R, Niewczas MA, Altintas MM, Pezzolesi MG, et al. Role of podocyte B7-1 in diabetic nephropathy. J Am Soc Nephrol. 2014;25(7):1415-29. doi: 10.1681/ASN.2013050518.
  12. Kim NH. Podocyte hypertrophy in diabetic nephropathy. Nephrology (Carlton). 2005; 10 Suppl: S14-6.

Download Article
Received September 23, 2019.
Accepted November 14, 2019.
©2019 International Medical Research and Development Corporation.