RELATIONSHIP BETWEEN OXIDANT AND ANTIOXIDANT ENZYMES STATUS IN TYPE 2 DIABETIC PATIENTS WITH NEPHROPATHY IN SAUDI POPULATION.

Authors

  • Ramprasad Nagarajrao Department of Medical Laboratory Science, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah, Kingdom of Saudi Arabia.
  • Samir Abdulkarim Alharbi Department of Medical Laboratory Science, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah, Kingdom of Saudi Arabia.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i1.22940

Keywords:

Type 2 diabetes mellitus, Diabetic nephropathy, Oxidative stress, Antioxidant enzymes, Malondialdehyde, Glycosylated hemoglobin, microalbuminuria

Abstract

 Objective: Oxidative stress has crucial role in pathogenesis of diabetic complications. Diabetic nephropathy (DN) is an important microvascular complication of diabetes and is widely recognized as the most common cause of the end-stage renal disease (ESRD) seen in clinical practice. Chemically, oxidative stress occurs as a result of increased levels of lipid peroxides and free radical intermediates, as well as a decrease in the total antioxidant capacity. This study analyzed the relationships between oxidant and antioxidant markers of DN in patients with type 2 diabetes mellitus (T2DM).

Methods: A descriptive study was taken during the period from November 2016 to August 2017. The present study included 53 patients suffering from T2DM without nephropathy and 51 patients T2DM with nephropathy along with 69 age- and sex-matched healthy controls. Various biochemical parameters, antioxidant enzymes, and malondialdehyde (MDA) levels were measured and compared.

Results: The glycosylated hemoglobin (HbA1c), urea, creatinine, microalbuminuria, and MDA levels were significantly increased (p<0.001), and antioxidant enzyme activities such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CTL) were significantly decreased (p<0.001) in T2DM with nephropathy patients followed by T2DM without nephropathy and control groups. There were a good negative correlations of HbA1c and GPx (r=−0.79), SOD (r=−0.61) and CTL (r=−0.74) (p≤0.05), whereas there was an excellent positive correlation of MDA concentration (r=0.85, p≤0.05) with HbA1c levels in diabetes with nephropathy.

Conclusion: The study illustrated that, in diabetic patients, there is an increased concentration of lipid peroxides which may contribute to decreased levels of cellular antioxidant enzymes, further leading to T2DM with nephropathy. Hence, monitoring of these antioxidant enzymes and microalbuminuria parameters in the early stage of diabetic patients could be vital importance in possible preventing further development of complications. We suggest potential and new multiproperty antioxidants therapy as one of the most important treatment strategies for diabetic patients without nephropathy for the prevention and slowing of diabetic with nephropathy before reaching to ESRD.

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References

Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J 2012;12:5-18.

Kumawat M, Sharma TK, Singh I, Singh N, Ghalaut VS, Vardey SK, et al. Antioxidant enzymes and lipid peroxidation in Type 2 diabetes mellitus patients with and without nephropathy. N Am J Med Sci 2013;5:213-9.

Gnudi L. Cellular and molecular mechanisms of diabetic glomerulopathy. Nephrol Dial Transplant 2012;27:2642-9.

Shao N, Kuang HY, Wang N, Gao XY, Hao M, Zou W, et al. Relationship between oxidant/Antioxidant markers and severity of microalbuminuria in the early stage of nephropathy in Type 2 diabetic patients. J Diabetes Res 2013;2013:232404.

Wolf G, Thaiss F. Hyperglycaemia-Pathophysiological aspects at the cellular level. Nephrol Dial Transplant 1995;10:1109-12.

Stehouwer CD. Endothelial dysfunction in diabetic nephropathy: State of the art and potential significance for non-diabetic renal disease. Nephrol Dial Transplant 2004;19:778-81.

Mahbood MF, Rahman PG. Serum lipid peroxidation and antioxidant enzyme levels in male and female diabetic subjects. Singapore Med J 2005;46:322-4.

Tavafi M. Diabetic nephropathy and antioxidants. J Nephropathol 2013;2:20-7.

World health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF consultation. World health Organization; 2006. p. 1-46.

Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes 1983;32 Suppl 2:64-78.

Trinder P. Blood sugar estimation by GOD- POD method. Ann Clin Biochem 1969;6:24-7.

Karl J, Burns G, Engel WD, Finke A, Krantzer M, Rolliner W, et al. Development and standardization of a new immunoturbidimetric HbA1c assay. Clin Lab 1993;39:991-6.

Gey KF, Brubacher GB, Stähelin HB. Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer. Am J Clin Nutr 1987;45:1368-77.

Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.

Arthur JR, Boyne R. Superoxide dismutase and glutathione peroxidase activities in neutrophils from selenium deficient and copper deficient cattle. Life Sci 1985;36:1569-75.

Beers RF Jr, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 1952;195:133-40.

Yagi K. Lipid peroxides and human disease. Chem Phy lipids 1987;45:337-51.

Singh N, Sharma P, Garg V, Mondal S, Singh A. Antioxidant therapy in diabetic nephropathy. J Pharm Res 2011;4:4249-51.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010;107:1058-70.

Krishan P, Chakkarwar VA. Diabetic nephropathy: Aggressive involvement of oxidative stress. J Pharm Edu Res 2011;2:35-41.

Park IS, Kiyomoto H, Abboud SL, Abboud HE. Expression of transforming growth factor-beta and Type IV collagen in early streptozotocin-induced diabetes. Diabetes 1997;46:473-80.

Lee WC, Wang CJ, Lee HJ. Antioxidants in decelerating diabetic nephropathy. Intech. DOI: 10.5772/45927; 387-399.

Spurney RF, Coffman TM. Stressed-out podocytes in diabetes? J Am Soc Nephrol 2008;19:2035-7.

Zimmerman FH, Cameron A, Fisher LD, Ng G. Myocardial infarction in young adults: Angiographic characterization, risk factors and prognosis (Coronary artery surgery study registry). J Am Coll Cardiol 1995;26:654-61.

Baggio B, Budakovic A, Dalla Vestra M, Saller A, Bruseghin M, Fioretto P, et al. Effects of cigarette smoking on glomerular structure and function in Type 2 diabetic patients. J Am Soc Nephrol 2002;13:2730-6.

Yoshida T, Tuder RM. Pathobiology of cigarette smoker induced chronic obstructive pulmonary disease. Physiol Rev 2007;87:1047-82.

Zhai S, Wang ZJ. Association of visceral adiposity with urinary albumin excretion in Type 2 diabetics. Zhonghua Yi Xue Za Zhi 2011;91:2108-11.

Varma V, Varma M, Sarkar PD, Varma A, Vyas S, Kulkarani R. Correlation of vitamin C with HbA1c and oxidative stress in diabetes mellitus with or without nephropathy. Natl J Med Res 2014;4:151-5.

Hanai K, Babazono T, Nyumura I, Toya K, Ohta M, Bouchi R, et al. Involvement of visceral fat in the pathogenesis of albuminuria in patients with Type 2 diabetes with early stage of nephropathy. Clin Exp Nephrol 2010;14:132-6.

Gupta MM, Chari S. Lipid peroxidation and antioxidant status in patients with diabetic retinopathy. Indian J Physiol Pharmacol 2005;49:187-92.

Kedziora-Kornatowska KZ, Luciak M, Blaszczyk J, Pawlak W. Lipid peroxidation and activities of antioxidant enzymes in erythrocytes of patients with non-insulin dependent diabetes with or without diabetic nephropathy. Nephrol Dial Transplant 1998;13:2829-32.

Conz PA, Bevilacqua PA, LaGreca G, Danieli D, Rodighiero MP, Cavarretta L, et al. Phospholipid hydroperoxidase glutathione peroxidase in the normal human kidney: A possible role in protecting cell membranes. Exp Nephrol 1993;1:376-8.

Bhatia S, Shukla R, Venkata Madhu S, Kaur Gambhir J, Madhava Prabhu K. Antioxidant status, lipid peroxidation and nitric oxide end products in patients of Type 2 diabetes mellitus with nephropathy. Clin Biochem 2003;36:557-62.

Waggiallah H, Alzohairy M. The effect of oxidative stress on human red cells glutathione peroxidase, glutathione reductase level, and prevalence of anemia among diabetics. N Am J Med Sci 2011;3:344-7.

Sundaram RK, Bhaskar A, Vijayalingam S, Viswanathan M, Mohan R, Shanmugasundaram KR, et al. Antioxidant status and lipid peroxidation in Type II diabetes mellitus with and without complications. Clin Sci (Lond) 1996;90:255-60.

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;26:1246-50.

Moussa SA. Oxidative stress in diabetes mellitus. Rom J Biophys 2008;18:225-36.

Arai K, Lizuka S, Tada Y, Oilkawa K, Taniguelui N. Increase in the glycosylated form of erythrocyte Cu Zn SOD diabetes and association of non-enzymatic glycosylation with enzyme activity. Biochem Biophys Acta 1987;924:292-6.

Gerli GC, Beretta L, Bianchi M, Pellegatta A, Agostoni A. Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities in beta-thalassaemia (major and minor). Scand J Haematol 1980;25:87-92.

Selvam R, Anuradha CV. Lipid peroxidation and antiperoxidative enzyme changes in erythrocytes in diabetes mellitus. Indian J Biochem Biophys 1988;25:268-72.

Hwang I, Lee J, Huh JY, Park J, Lee HB, Ho YS, et al. Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction. Diabetes 2012;61:728-38.

Tilton WM, Seaman C, Carriero D, Piomelli S. Regulation of glycolysis in the erythrocyte: Role of the lactate/pyruvate and NAD/NADH ratios. J Lab Clin Med 1991;118:146-52.

Ogawa S, Nako K, Okamura M, Senda M, Mori T, Ito S, et al. Aliskiren reduces albuminuria and oxidative stress, and elevates glomerular filtration rates in Japanese patients with advanced diabetic nephropathy. Hypertens Res 2011;34:400-1.

Tseng TH, Kao TW, Chu CY, Chou FP, Lin WL, Wang CJ, et al. Induction of apoptosis by hibiscus protocatechuic acid in human leukemia cells via reduction of retinoblastoma (RB) phosphorylation and bcl-2 expression. Biochem Pharmacol 2000;60:307-15.

Wang SC, Lee SF, Wang CJ, Lee CH, Lee WC, Lee HJ. Aqueous Extract from Hibiscus sabdariffa Linnaeus ameliorate diabetic nephropathy via regulating oxidative status and Akt/Bad/14-3-3 {gamma} in an experimental animal model. Evid-Based Complement Alternat Med 2011;938126. DOI: 10.1093/ecam/nep181. Epub 2011 Feb 20.

Wang GG, Lu XH, Li W, Zhao X, Zhang C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid Based Complement Alternat Med 2011;2011:323171.

Fallahzadeh MK, Dormanesh B, Sagheb MM, Roozbeh J, Vesssal G, Pakfetrat M. Effect of addition of silymarin to rennin-angiotension system inhibitors on proteinuria in Type 2 diabetic patients with overt nephropathy: A randomized, double-blind, placebo-controlled trail. Am J Kidney Dis 2012;60:896-903.

Al-Waili N, Al-Waili H, Al-Waili T, Salom K. Natural antioxidants in the treatment and prevention of diabetic nephropathy; a potential approach that warrants clinical trials. Redox Rep 2017;22:99-118.

Published

01-01-2018

How to Cite

Nagarajrao, R., and S. A. Alharbi. “RELATIONSHIP BETWEEN OXIDANT AND ANTIOXIDANT ENZYMES STATUS IN TYPE 2 DIABETIC PATIENTS WITH NEPHROPATHY IN SAUDI POPULATION”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 1, Jan. 2018, pp. 363-8, doi:10.22159/ajpcr.2018.v11i1.22940.

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