Diabetic nephropathy (DN) is one of the most common devastating complication of diabetes mellitus. Several studies tried to find drugs that could hinder it or prevent it. The current study aims to compare between the effects of Gum Arabic and Omega-3 fatty acids administration on the plasma level of kidney injury molecule (KIM -1) and kidney functions in an experimentally induced model of early diabetic nephropathy in rats.

Methods: Forty male albino rats were randomly assigned to four groups (n= 10 each): Group I (healthy control), group II (untreated diabetic control), group III (diabetic rats that received Gum arabic in a dose of 7.5 g/kg/day for 3 weeks) and group IV (diabetic rats that received Omega-3 fatty acids in a dose of 400 mg/kg/day for3 weeks after diagnosis of diabetes mellitus).

Results: Gum Arabic supplementation significantly decreased KIM-1, fasting blood glucose, proteinuria in the second and third week and improved creatinine clearance when compared to untreated diabetic rats. On the other hand, Omega-3 FA supplementation significantly decreased proteinuria in the second and third weeks compared to untreated diabetic group but it did not show significant effects on the other parameters.

Conclusion: GA is beneficial and may hinder the development of early diabetic nephropathy.

Keywords: Kidney injury molecule-1, Experimentally induced diabetes mellitus, Diabetic nephropathy, Kidney functions, Gum Arabic, Omega-3 fatty acids, Streptozotocin.

1. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.
2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37:81-90.
3. Abdel-Rahman EM, Saadulla L, Reeves WB, Awad AS. Therapeutic modalities in diabetic nephropathy: Standard and emerging approaches. J Gen Intern Med. 2012; 27 :458–68.
4. Musa H, Ahmed A, Fedail J, Musa T, Sifaldin A. Gum Arabic attenuates the development of nephropathy in type 1 diabetes. In: Gums and stabilisers for the food industry 18: Hydrocolloid functionality for affordable and sustainable global food solutions. 2016. p. 245–55.
5. Lelon JK, Jumba IO, Keter JK, Chemuku W, Oduor FDO. Assessment of physical properties of gum arabic from Acacia senegal varieties in Baringo District, Kenya. African J Plant Sci. 2010;4:95–8.
6. Ali BH, Beegam S, Al-Lawati I, Waly MI, Al za’abi M, Nemmar A. Comparative efficacy of three brands of gum acacia on adenine-Induced chronic renal failure in rats. Physiol Res. 2013;62:47–56.
7. Saunders A V, Davis BC, Garg ML. Omega-3 polyunsaturated fatty acids and vegetarian diets. Med J Aust. 2013;199:22–6.
8. Lauretani F, Semba RD, Bandinelli S, Miller ER, Ruggiero C, Cherubini A, et al. Plasma polyunsaturated fatty acids and the decline of renal function. Clin Chem. 2008;54:475–81.
9. Han E, Yun Y, Kim G, Lee Y, Wang HJ, Lee B-W, et al. Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia. PLoS One. 2016;11:0154683.
10. Itsiopoulos C, Marx W, Mayr HL, Tatucu-Babet OA, Dash SR, George ES, et al. The role of omega-3 polyunsaturated fatty acid supplementation in the management of type 2 diabetes mellitus: A narrative review. J Nutr Intermed Metab. 2018;14:42–51.
11. Ahmed S a, Hamed M a. Kidney injury molecule-1 as a predicting factor for inflamed kidney, diabetic and diabetic nephropathy Egyptian patients. J Diabetes Metab Disord. 2015;14:6.
12. El-Ashmawy NE, El-Zamarany EA, Khedr NF, Abd El-Fattah AI, Eltoukhy SA. Kidney injury molecule-1 (Kim-1): an early biomarker for nephropathy in type II diabetic patients. Int J Diabetes Dev Ctries. 2015;35:431–8.
13. V. B. Kidney injury molecule-1 (KIM-1): A urinary biomarker and much more. Vol. 24, Nephrology Dialysis Transplantation. Oxford University Press; 2009. p. 3265–8.
14. Aslan O, Demir M, Koseoglu M. Kidney Injury Molecule Levels in Type 2 Diabetes Mellitus. J Clin Lab Anal. 2016;30:1031–6.
15. Nowak N, Skupien J, Niewczas MA, Yamanouchi M, Major M, Croall S, et al. Increased plasma kidney injury molecule-1 suggests early progressive renal decline in non-proteinuric patients with type 1 diabetes. Kidney Int. 2016;89:459–67.
16. Goyal SN, Reddy NM, Patil KR, Nakhate KT, Ojha S, Patil CR, et al. Challenges and issues with streptozotocin-induced diabetes – A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact. 2016;244:49–63.
17. GS, . LP. Hypoglycaemic and Antihyperglycaemic Effect of Syzygium cumini Bark in Streptozotocin-Induced Diabetic Rats. J Pharmacol Toxicol. 2008;3:1–10.
18. Gado A, Aldahmash B. Antioxidant effect of Arabic gum against mercuric chloride-induced nephrotoxicity. Drug Des Devel Ther. 2013;7:1245.
19. Tulubas F, Gurel A, Oran M, Topcu B, Caglar V, Uygur E. The protective effects of ω-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats. Toxicol Ind Health. 2015;31:638–44.
20. Trinder P. Determination of glucose in blood using glucose oxidase eith an alternative oxygen acceptor. Ann clin Biochem. 1969;6:24–7.
21. Doumas BT. Standards for total serum protein assays: a collaborative study. Clin Chem. 1975;21:1159–66.
22. Patton CJ, Crouch SR. Spectrophotometric and kinetics investigation of the Berthelot reaction for the determination of ammonia. Anal Chem. 1977;49:464–9.
23. Bartels H, Böhmer M, Heierli C. Serum kreatininbestimmung ohne enteiweissen. Clin Chim Acta. 1972;37:193–7.
24. Duarte CG, Preuss HG. Assessment of renal function--glomerular and tubular. Clin Lab Med. 1993;13:33–52.
25. Jin Y, Shao X, Sun B, Miao C, Li Z, Shi Y. Urinary kidney injury molecule-1 as an early diagnostic biomarker of obstructive acute kidney injury and development of a rapid detection method. Mol Med Rep. 2017;15:1229–35.
26. Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic Kidney Disease: Worldwide Difference of Prevalence and Risk Factors. J Nephropharmacol. 2016;5:49–56.
27. Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM, Brinkley LJ. Beneficial Effects of High Dietary Fiber Intake in Patients with Type 2 Diabetes Mellitus. N Engl J Med. 2000;342:1392–8.
28. Nasir O, Umbach AT, Rexhepaj R, Ackermann TF, Bhandaru M, Ebrahim A, et al. Effects of gum arabic (Acacia senegal) on renal function in diabetic mice. Kidney Blood Press Res. 2012;35:365–72.
29. Chen C, Yu X, Shao S. Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: A meta-analysis. PLoS One. 2015;10:1–14.
30. Garman JH, Mulroney S, Manigrasso M, Flynn E, Maric C. Omega-3 fatty acid rich diet prevents diabetic renal disease. AJP Ren Physiol. 2009;296:306–16.
31. Lee SM, Chung SH, Park Y, Park MK, Son YK, Kim SE, et al. Effect of Omega-3 Fatty Acid on the Fatty Acid Content of the Erythrocyte Membrane and Proteinuria in Patients with Diabetic Nephropathy. Int J Endocrinol. 2015:208121.
32. Ahmad J. Management of diabetic nephropathy: Recent progress and future perspective. Diabetes Metab Syndr Clin Res Rev. 2015;9:343–58.
33. Vergouwe Y, Soedamah-Muthu SS, Zgibor J, Chaturvedi N, Forsblom C, Snell-Bergeon JK, et al. Progression to microalbuminuria in type 1 diabetes: Development and validation of a prediction rule. Diabetologia. 2010;53:254–62.
34. Giunti S, Barit D, Cooper ME. Mechanisms of diabetic nephropathy: role of hypertension. Hypertens (Dallas, Tex 1979). 2006;48:519—526.
35. Hassan AED, Shaat EA, Deif MM, El Azhary NM, Omar EM. Effect of erythropoietin hormone supplementation on renal functions and the level of hypoxia-inducible factor-1α in rat kidneys with experimentally induced diabetic nephro-pathy. Alexandria J Med. 2014;50:69–75.
36. Jia Q, Yang R, Liu X, Ma S, Wang L. Genistein attenuates renal fibrosis in streptozotocin‑induced diabetic rats. Mol Med Rep. 2018;423–31.
37. Montero A, Munger KA, Khan RZ, Valdivielso JM, Morrow JD, Guasch A, et al. F2-isoprostanes mediate high glucose-induced TGF-β synthesis and glomerular proteinuria in experimental type I diabetes. Kidney Int. 2000;58:1963–72.
38. Ali BH, Al-Husseni I, Beegam S, Al-Shukaili A, Nemmar A, Schierling S, et al. Effect of Gum Arabic on Oxidative Stress and Inflammation in Adenine-Induced Chronic Renal Failure in Rats. PLoS One. 2013;8.
39. Miller PE, Van Elswyk M, Alexander DD. Long-chain Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: A meta-analysis of randomized controlled trials. Am J Hypertens. 2014;27:885–96.
40. De Caterina R, Madonna R, Bertolotto A, Schmidt EB. n-3 fatty acids in the treatment of diabetic patients: Biological rationale and clinical data. Vol. 30, Diabetes Care. 2007. p. 1012–26.
41. Watson H, Mitra S, Croden FC, Taylor M, Wood HM, Perry SL, et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut. 2017;gutjnl-2017-314968.
42. Oh da Y, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, et al. GPR120 Is an ω-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects. Cell. 2010;142:687–98.
43. Vemuri M, Kelley DS, Mackey BE, Rasooly R, Bartolini G. Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Prevents Trans-10, Cis-12 Conjugated Linoleic Acid (CLA)-Induced Insulin Resistance in Mice. Metab Syndr Relat Disord. 2007;5:315–22.
44. Iii ERM, Juraschek SP, Appel LJ, Madala M, Anderson C a M, Bleys J. The effect of n – 3 long-chain polyunsaturated fatty acid supplementation on urine protein excretion and kidney function : meta-analysis of clinical trials 1 – 3. Am J Clin Nutr. 2009: 1937–45.
45. Foggensteiner L, Mulroy S, Firth J. Management of diabetic nephropathy. J R Soc Med. 2001;94:210–7.
46. Castro BBA de, Colugnati FAB, Cenedeze MA, Suassuna PG de A, Pinheiro HS. Standardization of renal function evaluation in Wistar rats ( Rattus norvegicus ) from the Federal University of Juiz de Fora’s colony. J Bras Nefrol. 2014;36:139–49.
47. National Clinical Guideline Centre. Chronic kidney disease (partial update): Early identification and management of chronic kidney disease in adults in primary and secondary care. Natl Inst Heal Care Excell. 2014;1–449.
48. Ali BH, Alqarawi AA, Ahmed IH. Does treatment with gum Arabic affect experimental chronic renal failure in rats? Fundam Clin Pharmacol. 2004;18:327–9.
49. Nasir O. Renal and extrarenal effects of gum arabic (Acacia senegal) - What can be learned from animal experiments? Kidney Blood Press Res. 2013;37:269–79.
50. Nasir O, Artunc F, Saeed A, Kambal MA, Kalbacher H, Sandulache D, et al. Effects of Gum Arabic (Acacia senegal) on Water and Electrolyte Balance in Healthy Mice. J Ren Nutr. 2008;18:230–8.
51. Ali BH, Al Za’abi M, Al Shukaili A, Nemmar A. High-mobility group box-1 protein in adenine-induced chronic renal failure and the influence of gum arabic thereon. Physiol Res. 2015;64:147–51.
52. Suleimani YMAL, Ramkumar A, Mahruqi ASAL, Tageldin MH, Nemmar A, Ali BH. Influence of treatment with gum acacia on renal vascular responses in a rat model of chronic kidney disease. Eur Rev Med Pharmacol Sci. 2015;19:498–506.
53. Soleimani A, Taghizadeh M, Bahmani F, Badroj N, Asemi Z. Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2015:1–6.
54. Bonventre J V. Kidney Injury Molecule‐1 (KIM‐1): A specific and sensitive biomarker of kidney injury. Scand J Clin Lab Invest. 2008;68:78–83.
55. Nauta FL, Boertien WE, Bakker SJL, Van Goor H, Van Oeveren W, De Jong PE, et al. Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care. 2011;34:975–81.
56. Ichimura T, Bonventre J V., Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273:4135–42.
57. Han WK, Bailly V, Abichandani R, Thadhani R BJ. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62:237–44.
58. Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre J V. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Physiol. 2006;290:517–29.
59. Han WK, Alinani A, Wu C-L, Michaelson D, Loda M, McGovern FJ, et al. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol. 2005;16:1126–34.
60. Ali BH, Al-Salam S, Al Husseni I, Kayed RR, Al-Masroori N, Al-Harthi T, et al. Effects of Gum Arabic in rats with adenine-induced chronic renal failure. Exp Biol Med (Maywood). 2010;235:373–82.
61. Ali BH, Ziada A, Al Husseni I, Beegam S, Nemmar A. Motor and behavioral changes in rats with adenine-induced chronic renal failure: Influence of acacia gum treatment. Exp Biol Med. 2011;236:107–12.
62. Suliman SM, Hamdouk MI, Elfaki MB. Gum Arabic fiber as a supplement to low protein diet in chronic renal failure patients. Sudan Association of Physicians. In: 17th Conference Khartoum. 2000.

Pr. Patricia Sidrak

Department of Medical Physiology, Faculty of Medicine, Alexandria University, Egypt