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type 1 diabetes mellitus, diabetic nephropathy, oxidative stress, pharmacological nephroprotection

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Khaitovych, M., & Ivchenko, M. (2017). MODERN TRENDS OF MEDICAL NEPHROPROTECTION IN TYPE 1 DIABETES MELLITUS. Medical Science of Ukraine (MSU), 12(3-4), 122-128. Retrieved from


Resume. Type 1 diabetes mellitus is one of the widespread endocrinological diseases in the world that has a stable growth dynamics. Diabetes mellitus is characterized by the development of severe disabling complications, including diabetic kidney disease (diabetic nephropathy) is one of the most dangerous.

The pathogenesis of diabetic nephropathy comprehensive and includes the following components: hereditary, metabolic (hyperglycemia, hyperlipidemia, hyperuricemia), hemodynamic (intraglomerular hypertension, arterial hypertension), hormonal (hyperinsulinemia, activation of the renin-angiotensin-aldosterone system), immune (imbalance in the production of pro- and anti-inflammatory cytokines, growth factors, etc.) violations.

In many tissues hyperglycemia leads to the generation of free radicals. In the absence of adequate compensatory response by the endogenous antioxidant system in the body oxidative imbalance occurs leading to activation of stress-sensitive signaling pathways involving transcriptional factor NF-kB, mitogen-activated protein kinase, protein kinase C. The result is the synthesis of gene products causing cell injury, inflammation and apoptosis, which eventually leads to the development of late diabetic complications.

Lately, the nephroprotective properties of variable antioxidant compounds of nature and synthetic origin (including bioflavonoids, vitamin D3, ibuprofen, N-acetylcysteine etc.) for complex treatment of type 1 diabetes mellitus and its complications (especially diabetic nephropathy) has been actively discussed.

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1. Babenko A.Yu., Bayrasheva V.K. Diabeticheskaya nefropatiya. Zavisit li renoprotektsiya ot vybora sakharosnizhayushchey terapii? // Meditsinskiy sovetnik. 2015. No. 7. P. 32-43 [in Russian].
2. Den'gin V.V. Perspektivnyye napravleniya klinicheskogo primeneniya N-atsetiltsisteina // Farmateka. 2008. No. 4. P. 48-52 [in Russian].
3. Ivanov D.D. Diabeticheskaya nefropatiya: diagnostika i lecheniye v svete rekomendatsiy ADA 2011 // Zdorovia Ukrainy. 2011. No. 1 (15). P. 27 [in Russian].
4. Maidannyk V.H., Burlaka Ye.A. Stan metabolichno-hipoksychnykh porushen pry diabetychnii nefropatii u ditei // Eksperymentalna ta klinichna fiziolohiia i biokhimiia. 2015. No. 4. P. 47-55 [in Ukrainian].
5. Rasin M.S., Borzykh O.A., Mormol' I.A. Rol' retseptorov, aktiviruyushchikh proliferatsiyu peroksisom, v fiziologii i patologii pochek // Nefrologiya. 2013. Vol. 17, No. 4. P. 44-48 [in Russian].
6. Tugusheva F.A., Zubina I.M. Oksidativnyy stress i yego uchastiye v neimmunnykh mekhanizmakh progressirovaniya khronicheskoy bolezni pochek // Nefrologiya. 2009. Vol.13, No. 3. P. 42-48 [in Russian].
7. Unifikovanyi klinichnyi protokol pervynnoi, ekstrenoi, vtorynnoi (spetsializovanoi) ta tretynnoi (vysokospetsializovanoi) medychnoi dopomohy. Tsukrovyi diabet 1 typu u molodykh liudei ta doroslykh // Nakaz Ministerstva okhorony zdorovia Ukrainy vid 29 hrudnia 2014 № 1021 [in Ukrainian].
8. Ahmad A., Mondello S., Di Paola R. [et al.]. Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: a comparison with n-acetylcysteine // Eur. J. Pharmacol. 2012. Vol. 674, No. 2-3. Р. 397-406. Mode of access:
9. Akira Mima. Inflammation and Oxidative Stress in Diabetic Nephropathy: New Insights on Its Inhibition as New Therapeutic Targets // Journal of Diabetes Research. 2013. Access mode: articles/PMC3686081/
10. Al-Rasheed N.M., Al-Amin M.A., Hasan I.H. [et al.]. Fenofibrate attenuates diabetic nephropathy in experimental diabetic rat's model via suppression of augmented TGF-β1/Smad3 signaling pathway // Arch Physiol Biochem. 2016. Vol. 122, No. 4. Р. 186-194. Access mode:
11. Asmat U., Abad K., Ismail K. Diabetes mellitus and oxidative stress – A concise review // Saudi Pharmaceutical Journal. 2016. Vol. 24, No. 5. Р. 547-553. Access mode: /PMC5059829/
12. Bhattacharjee N., Barma S., Konwar N. [et al.]. Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update // Eur J Pharmacol. 2016. Vol. 79. Р. 8-24.
13. Chowdhury R., Kunutsor S., Vitezova A. Vitamin D and risk of cause specific death: systematic review and metaanalysisof observational cohort and randomised intervention studies // British Medical Journal. 2014. Vol. 348. Р. 1-13.
14. Dronavalli S., Duka I., Bakris G.L. The pathogenesis of diabetic nephropathy // Nat. Clin. Pract. Endocrinol. Metab. 2008. Vol. 4, No. 8. Р. 444-452.
15. Elmas O., Erbas O., Yigitturk G. The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model // Biomed Pharmacother. 2016. Vol. 83. Р. 392-396.
16. Evans J.L., Goldfine I.D., Maddux B.A., Grodsky G.M. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes // Endocrine Rev. 2002. Vol. 23, No. 5. P. 599-622.
17. Giacco F., M. Brownlee. Oxidative stress and diabetic complications // Circ. Res. 2010. Vol. 107, Suppl. 9. P. 1058-1070.
18. Goldin A., Beckman J.A., Schmidt A.M., Creager M.A. Advanced glycation and products: sparking the developmentof diabetic vascular injury // Circulation. 2006. Vol. 114. P. 597-605.
19. Gomes I.B., Porto M.L., Santos M.C. [et al.]. Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy // Lipids Health Dis. 2014. Vol. 13. Р. 184. Access mode:
20. Guo C., Ding G., Huang W. [et al.] Total saponin of Dioscoreae hypoglaucae rhizoma ameliorates streptozotocin-induced diabetic nephropathy // Drug. Des. Devel. Ther. 2016. Vol. 10. Р. 799-810.
21. Haleagrahara N., Yee T.M., Chakravarthi S., Lee N. Protective effect of N-acetylcysteine on cyclosporine A-induced changes in lipid hydroperoxide levels and renal dysfunction in rats // Arch. Med. Sci. 2009. Vol. 5. Р. 16-22.
22. Hamza A.H., Al-Bishri W.M., Damiati L.A., Ahmed H.H. Mesenchymal stem cells: a future experimental exploration for recession of diabetic nephropathy // Renal Failure. 2016. Vol. 39, No. 1. Р. 67-76.
23. Holick M.F. Medical progress: Vitamin D deficiency // NEJM. 2007. Vol. 357, Issue 3. P. 266-281.
24. Ibrahim D.S., Abd El-Maksoud M.A. Effect of strawberry (Fragaria ananassa) leaf extract on diabetic nephropathy in rats // Int. J. Exp. Pathol. 2015. Vol. 96, No. 2. Р. 87-93. Access mode:
25. Kang X., Hu D.Y., Li C.B. [et al.]. N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with pre-existing renal insufficiency or diabetes: a systematic review and meta-analysis // Ren Fail. 2015. Vol. 37, No. 10. Р. 297-303.
26. Kashihara N., Haruna Y., Kondeti V.K., Kanwar Y.S. Oxidative stress in diabetic nephropathy // Curr. Med. Chem. 2010. Vol. 17, No. 34. Р. 4256-4269. Access mode: PMC3708695/
27. Lee E.S., Kim H.M., Kang J.S. [et al.]. Oleanolic acid and N-acetylcysteine ameliorate diabetic nephropathy through reduction of oxidative stress and endoplasmic reticulum stress in a type 2 diabetic rat model // Nephrol Dial Transplant. 2016. Vol. 31, No. 3. Р. 391-400.
28. Liu Y.W., Zhu X. Ibuprofen attenuates nephropathy in streptozotocin induced diabetic rats // Mol. Med. Rep. 2016. Vol. 13, No. 6. Р. 5326-5334.
29. Majid Tavafi. Diabetic nephropathy and antioxidants // Journal of Nephropathology. 2013. Vol. 2, No. 1. Р. 20-27. Access mode:
30. Manjula Ramen T. Depletion of Glutathione during Oxidative Stress and Efficacy of N-Acetyl Cysteine: An Old Drug with New Approaches // Med chem. 2015. Vol. 5. P. 37-39.
31. Minaz N., Razdan R. Therapeutic insight into molsidomine, a nitric oxide donor in streptozotocin-induced diabeticnephropathy in rats // Indian J. Pharmacol. 2016. Vol. 48, No. 5. Р. 544-549. Access mode:
32. Mironidou-Tzouveleki M., Tsartsalis S., Tomos C. Vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic nephropathy of type 1 diabetes mellitus // Curr Drug Targets. 2011. Vol. 12, No. 1. Р. 107-114.
33. Rahimi-Madiseh M., Malekpour-Tehrani A., Bahmani M., Rafieian-Kopaei M. The research and development on the antioxidants in prevention of diabetic complications // Asian Pacific Journal of Tropical Medicine. 2016. Vol. 9, Issue 9. P. 825-831. Access mode:
34. Niu H.S., Liu I.M., Niu C.S. [et al.]. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats // Drug Des Devel Ther. 2016. Vol. 10. Р. 971-978. Access mode: PMC4780717/
35. Oh J., Weng S., Felton S.K. 1,25(OH) 2 vitamin D inhibits foam cell formation andsuppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus // Circulation. 2009. Vol. 120. P. 687-698.
36. Pal P.B., Sinha K., Sil P.C. Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats // PLoS One. 2014. Vol. 9, No. 9:e107220. Access mode:
37. Park C.W., Zhang Y., Zhang X. [et al.]. PPARα agonist fenofibrate improves diabetic nephropathy in db/db mice // Kidney Int. 2006. Vol. 69, No. 9. P. 1511-1517.
38. Patel S., Santani D. Role of NF-B in the pathogenesis of diabetes and its associated complications // Pharmacological Reports. 2009. Vol. 61, No. 4. P. 595-603.
39. Reidy K., Kang H.M., Hostetter T., Susztak K. Molecular mechanisms of diabetic kidney disease // K. J. Clin. Invest. 2014. Vol. 124, Issue 6. P. 2333-2340.
40. Scott R., Best J., Forder P. Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481] // Cardiovasc Diabetol. 2005. Vol. 4. P. 13. Access mode:
41. Shimizu M.H.M., Danilovic A., Andrade L. [et al.]. N-acetylcysteine protects against renal injury following bilateral ureteral obstruction // Nephrol. Dial. Transplant. 2008. Vol. 10. Sup. 23. P. 3067-3073.
42. Tian Y., Lv G., Yang Y. [et al.]. Effects of vitamin D on renal fibrosis in diabetic nephropathy model rats // Int. J. Clin. Exp. Pathol. 2014. Vol. 7, No. 6. P. 3028-3037. Access mode:
43. Wang C., Min C., Rong X. [et al.] Irbesartan can improve blood lipid and the kidney function of diabetic nephropathy // Discov Med. 2015. Vol. 20, No. 108. P. 67-77.
44. Wang J., Liu H., Li N. [et al.]. The protective effect of fucoidan in rats with streptozotocin-induced diabetic nephropathy // Mar Drugs. 2014. Vol. 12, No. 6. P. 3292-3306. Access mode:
45. Wang L., Chen D., Cao J., Liu Z. Protective effect of N-acetylcysteine on experimental chronic cadmium nephrotoxicity in immature female rats // Hum Exp Toxicol. 2009. Vol. 28, No. 4. P. 221-229.
46. World Health Organization. Access mode:
47. Xin C., Xia Z., Jiang C. [et al.]. Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling // Drug Des Devel Ther. 2015. Vol. 9. P. 6269-6274. Access mode:
48. Xu H.Y., Liu M.M., Wang X., He X.Y. Association of angiotensin-converting enzyme insertion/deletion polymorphism with type 1 diabeticnephropathy: a meta-analysis // Ren Fail. 2016. Vol. 38, No. 9. P. 1320-1327.
49. Zemin C., Mark E.C. Pathogenesis of diabetic nephropathy // J. Diabetes Invest. 2011. Vol. 2. P. 243-247. Access mode:
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