Nephroprotective effect of silymarin in hyperglycemia-induced oxidative stress in rats
Keywords:Diabetes, Oxidative stress, Kidney, Silymarin
Background: Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia. Hyperglycemia is the etiological factor for oxidative stress-induced microvascular and macrovascular complications. Many animal experimental models and clinical trials have proved the antioxidant defense mechanism of flavonoids in ameliorating the progression of chronic diabetic complications. Hence, the objective of this study was to evaluate the nephroprotective effects of silymarin in alloxan induced Type I diabetes.
Methods: Male Wistar rats were divided into five groups of six each. Group I served as control. Group II, III, IV and V were diabetic rats. Group II diabetic rats received the vehicle. Groups III and IV were treated with 200 mg/kg and 400 mg/kg of silymarin, respectively. Group V was treated with glibenclamide (0.5 mg/kg). After 3 weeks, blood samples were collected from all the groups of animals to measure serum glucose, urea and creatinine. Lipid peroxidation study and histopathological study were conducted in the renal tissue to confirm the oxidative damage.
Results: The serum glucose, urea and creatinine significantly increased in untreated diabetic rats. In addition, there was a significant rise in lipid peroxidation with a glomerular atrophy and necrotic tubular epithelium in the renal tissue. The rise in serum glucose, urea and creatinine was ameliorated by silymarin. The renal tissue showed increased antioxidant levels, decreased lipid peroxides and only mild changes in glomeruli and tubules.
Conclusion: The results of this study indicate silymarin is an effective nutritional supplement to prevent complications of diabetes.
Triplitt CL, Reasner CA. Diabetes mellitus. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy - A Pathophysiologic Approach. 8th Edition, Volume 83. China: McGraw-Hill Companies; 2011:1255-302.
Martin NM, Bloom SR. Pancreatic endocrine disorders and multiple endocrine neoplasia. In: DA TM JD editors. Oxford Textbook of Medicine. 5th Edition. Volume 13.10. New York: Oxford University Press; 2010:1976-86.
Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, et al. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes. 1999;48(4):927-32.
Tokuyama Y, Sturis J, DePaoli AM, Takeda J, Stoffel M, Tang J, et al. Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat. Diabetes. 1995;44(12):1447-57.
Stahl W, Sies H. Antioxidant defense: vitamins E and C and carotenoids. Diabetes. 1997;46 Suppl 2:S14-8.
Ahmadvand H. Effects of coenzyme Q10 on hemoglobin A1C, serum urea and creatinine in alloxan-induced type 1 diabetic rats. Iran J Pharmacol Ther. 2012;11:64-7.
Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002;22:19 34.
Morazzoni P, Bombardelli E. Silybum marianum (Carduus marianus). Fitoterapia. 1995;64:3-42.
Rao BK, Kesavulu MM, Giri R, Appa Rao C. Antidiabetic and hypolipidemic effects of Momordica cymbalaria Hook fruit powder in alloxan-diabetic rats. J Ethnopharmacol. 1999;67(1):103-9.
Kumar S, Kumar D, Deshmukh RR, Lokhande PD, More SN, Rangari VD. Antidiabetic potential of Phyllanthus reticulatus in alloxan-induced diabetic mice. Fitoterapia. 2008;79(1):21-3.
Lal VK, Gupta PP, Awanish P. Hypoglycemic effect of kyllinga triceps in STZ induced diabetic rats. J Diabetes Metab. 2012;5.6:1000203.
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974;20(4):470-5.
Niehaus WG Jr, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem. 1968;6(1):126-30.
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70-7.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984;21(2):130-2.
Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389-94.
Al-Enazi MM. Combined therapy of rutin and silymarin has more protective effects on STZ-induced oxidative stress in rats. J Appl Pharm Sci. 2014;4(01):021-8.
Balkis Budin S, Othman F, Louis SR, Abu Bakar M, Radzi M, Osman K, et al. Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats. Rom J Morphol Embryol. 2009;50(1):23-30.
Garfinkel D, Zorin M, Wainstein J, Matas Z, Laudon M, Zisapel N. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes. 2011;4:307-13.
Arivazhagan P, Thilakavathy T, Panneerselvam C. Antioxidant lipoate and tissue antioxidants in aged rats. J Nutr Biochem. 2000;11(3):122-7.
Powers AC. Diabetes mellitus. In: Kasper DL, Faver AS, Longo D, Branunald E, Hauser SC, Janesen JL, editors. Harrison’s Principles of Internal Medicine. 16th Edition, Volume 323. New York: McGraw-Hill Book Co.; 2005: 2152 62.
Varzi HN, Esmailzadeh S, Morovvati H, Avizeh R, Shahriari A, Givi ME. Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs. J Vet Pharmacol Ther. 2007;30(5):477-81.