Serum Extracellular Superoxide Dismutase Concentration in Type 2 Diabetic Patients with Nephropathy: An Investigation of the Relationship

Main Article Content

Safa Zuhair AlRheem, Shawqi Watheq Mohammed Ali Altareehee, Hassnin Muiz Mohammad Hassan

Keywords

Extracellular Super Oxide Dismutase, SOD3, Diabetic Nephropathy, Oxidative Stress

Abstract

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease and is characterized by complex pathogenic mechanisms involving oxidative stress. Antioxidant enzymes play a crucial role in combating oxidative stress and potentially slowing down the progression of DN. Extracellular superoxide dismutase (EcSOD) is an important enzyme located in the extracellular spaces that scavenges the superoxide anion, a key contributor to oxidative stress.


Methods: In this study, we enrolled a total of 167 diabetic patients, with 101 patients without nephropathy serving as the control group. The DN group consisted of 66 patients, who were further categorized into subgroups based on their albumin creatinine ratio (ACR): microalbuminuria (ACR 30-300 mg/g) and macroalbuminuria (ACR > 300 mg/g). EcSOD enzyme concentrations were measured using the Enzyme-Linked Immuno-Sorbent Assay (ELISA) technique.


Results: The mean EcSOD concentration in the DN group was 166.18 ng/mL (±66.02), slightly higher than the diabetic-only group (157.68 ng/mL ±66.67), but this difference was not statistically significant (P value = 0.420). Within the DN group, the microalbuminuria subgroup exhibited an EcSOD concentration of 166.95 ng/mL (±68.83), while the macroalbuminuria subgroup showed a concentration of 159.73 ng/mL (±36.96). However, the comparison between these subgroups did not yield a statistically significant difference (P = 0.787).


Conclusions: Based on our findings, the concentration of EcSOD does not appear to be significantly associated with the development of nephropathy in Type 2 diabetic patients. Further investigations are warranted to explore other potential mechanisms contributing to the pathogenesis of diabetic nephropathy and to determine the role of EcSOD in this context

Abstract 98 | pdf Downloads 43

References

1. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al., Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020 Aug 30;21(17):6275.
2. Climie RE, van Sloten TT, Bruno RM, Taddei S, Empana JP, Stehouwer CDA, et al., Macrovasculature and Microvasculature at the Crossroads Between Type 2 Diabetes Mellitus and Hypertension. Hypertension. 2019 Jun;73(6):1138-1149.
3. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020 Feb 29;395(10225):709-733.
4. Hussain S, Jamali MC, Habib A, Hussain MS, Akhtar M, Najmi AK. Diabetic kidney disease: An overview of prevalence, risk factors, and biomarkers. Clinical Epidemiology and Global Health. 2021 Jan 1;9:2-6.
5. Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021 Sep;20(9):689-709.
6. Thakur P, Kumar A, Kumar A. Targeting oxidative stress through antioxidants in diabetes mellitus. J Drug Target. 2018 Nov;26(9):766-776.
7. Rosa AC, Corsi D, Cavi N, Bruni N, Dosio F. Superoxide Dismutase Administration: A Review of Proposed Human Uses. Molecules. 2021 Mar 25;26(7):1844.
8. Griess B, Tom E, Domann F, Teoh-Fitzgerald M. Extracellular superoxide dismutase and its role in cancer. Free Radic Biol Med. 2017 Nov;112:464-479.
9. Halim M, Halim A. The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes). Diabetes Metab Syndr. 2019 Mar-Apr;13(2):1165-1172.
10. Tan RJ, Zhou D, Xiao L, Zhou L, Li Y, Bastacky SI, Oury TD, et al., Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease. J Am Soc Nephrol. 2015 Oct;26(10):2447-59.
11. Hong YA, Lim JH, Kim MY, Kim Y, Park HS, Kim HW, et al., Extracellular Superoxide Dismutase Attenuates Renal Oxidative Stress Through the Activation of Adenosine Monophosphate-Activated Protein Kinase in Diabetic Nephropathy. Antioxid Redox Signal. 2018 Jun 10;28(17):1543-1561.
12. Sumida K, Nadkarni GN, Grams ME, Sang Y, Ballew SH, Coresh J, et al., Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis: An Individual Participant-Based Meta-analysis. Ann Intern Med. 2020 Sep 15;173(6):426-435.
13. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al., A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12.
14. Eddaikra A, Eddaikra N. Endogenous enzymatic antioxidant defense and pathologies. InAntioxidants-Benefits, Sources, Mechanisms of Action 2021 Jan 21. IntechOpen.
15. Ali MM, Mahmoud AM, Le Master E, Levitan I, Phillips SA. Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx. Am J Physiol Heart Circ Physiol. 2019 Mar 1;316(3):H647-H663.
16. Yan Z, Spaulding HR. Extracellular superoxide dismutase, a molecular transducer of health benefits of exercise. Redox Biol. 2020 May;32:101508.
17. Lewandowski Ł, Urbanowicz I, Kepinska M, Milnerowicz H. Concentration/activity of superoxide dismutase isozymes and the pro-/antioxidative status, in context of type 2 diabetes and selected single nucleotide polymorphisms (genes: INS, SOD1, SOD2, SOD3) - Preliminary findings. Biomed Pharmacother. 2021 May;137:111396.
18. Mimić-Oka J, Simić T, Djukanović L, Reljić Z, Davicević Z. Alteration in plasma antioxidant capacity in various degrees of chronic renal failure. Clin Nephrol. 1999 Apr;51(4):233-41.
19. Shurtz-Swirski R, Mashiach E, Kristal B, Shkolnik T, Shasha SM. Antioxidant enzymes activity in polymorphonuclear leukocytes in chronic renal failure. Nephron. 1995;71(2):176-9.
20. Modlinger PS, Wilcox CS, Aslam S. Nitric oxide, oxidative stress, and progression of chronic renal failure. Semin Nephrol. 2004 Jul;24(4):354-65.
21. Galvan DL, Badal SS, Long J, Chang BH, Schumacker PT, Overbeek PA, et al., Real-time in vivo mitochondrial redox assessment confirms enhanced mitochondrial reactive oxygen species in diabetic nephropathy. Kidney Int. 2017 Nov;92(5):1282-1287.
22. Fujita H, Fujishima H, Takahashi K, Sato T, Shimizu T, Morii T, et al., SOD1, but not SOD3, deficiency accelerates diabetic renal injury in C57BL/6-Ins2(Akita) diabetic mice. Metabolism. 2012 Dec;61(12):1714-24.
23. Kimura F, Hasegawa G, Obayashi H, Adachi T, Hara H, Ohta M, et al., Serum extracellular superoxide dismutase in patients with type 2 diabetes: relationship to the development of micro- and macrovascular complications. Diabetes Care. 2003 Apr;26(4):1246-50.
24. Guo H, Xu D, Kuroki M, Lu Z, Xu X, Geurts A, et al., Kidney failure, arterial hypertension and left ventricular hypertrophy in rats with loss of function mutation of SOD3. Free Radic Biol Med. 2020 May 20;152:787-796.
25. Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y, et al., Reduction of renal superoxide dismutase in progressive diabetic nephropathy. J Am Soc Nephrol. 2009 Jun;20(6):1303-13.