RUTIN RESTORE BIOCHEMICAL CHANGES, OXIDATIVE STRESS AND BETATROPHIN LEVEL IN STZ-INDUCED DIABETIC RATS
Keywords:Diabetes mellitus, STZ, Rutin, Betatrophin
Objective: Diabetes mellitus (DM) is associated with long-term damage, dysfunction, of various organs. Study aims to assessrole of rutin on experimentally induced diabetes.
Methods: 50 adult male albino rats divided into 5 groups. Group I (control group, rats were orally administered with 1 ml saline daily). Group II (DMSO group, rats were orally administered with 0.2 % DMSO for 60 d orally). Group III (positive control, animals were injected intraperitoneally with 60 mg/kg b. wtstreptozotocin followed by intraperitoneal injection with 120 mg/kg b. wt of Nicotinamide after 15 min). Group IV (therapeutic group, diabetic rats treated with 100 mg/kg b. wt of rutin for 60 d orally). Group V (standard group, diabetic animals treated with 100 mg/kg b. wt of metformin for 60 d orally). At the end of the experimental period blood serum and plasma, liver, kidney and pancreatic tissues were collected.
Results: Diabetic rats showed a significant increase in plasma glucose, serum urea, creatinine, cholesterol and triglyceride. Also, induced oxidative stress as pointed out an increase in MDA level, decrease in GSH level, GST and CAT activities in compared to control group. Also, showed an increase in plasma and tissues levels of betatrophin. Oral administration of rutin cause decrease in elevated biochemical and oxidative stress parameters. Also, decrease betatrophin level when compared with diabetic rats. Our results were confirmed by histopathological examination of different tissues.
Conclusion: This study suggests thatrutinexihibitsantihyperglycemic and antioxidant activity in streptozotocin-induced diabetic rats.
2. Doux SP, Woodley SE, Palton NJ, Wilson GL. Mechanism of nitrosourea induced cell damage: alteration in DNA. Diabetes 1986;35:866-72.
3. Portha B, Blondel O, Serradas P, McEvoy R, Giroix MH, Kergoat M, et al. The rat models of non-insuindependant diabetes induced by neonatal streptozotocin. Diabete Metab 1989;15:61-75.
4. Cao J, Zhang Y, Chen W, Zhao X. The relationship between fasting plasma concentrations of selected flavonoids and their ordinary dietary intake. Br J Nutr 2010;103:249–55.
5. Scholz S, Williamson G. Interactions affecting the bioavailability of dietary polyphenols in vivo. Int J Vitam Nutr Res 2007;77:224–35.
6. Mamani Matsuda M, Kauss T, Al-Kharrat A, Rambert J, Fawaz F, Thiolat D, et al. Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators. Biochem Pharmacol 2006;72:1304–10.
7. Valerio DA, Georgetti SR, Magro DA, Casagrande R, Cunha TM, Vicentini FT. Quercetin reduces inflammatory pain: inhibition of oxidative stress and cytokine production. J Nat Prod 2009;72:1975–9.
8. McAnulty SR, McAnulty LS, Nieman DC, Quindry JC, Hosick PA, Hudson MH, et al. Chronic quercetin ingestion and exercise-induced oxidative damage and inflammation. Appl Physiol Nutr Metab 2008;33:254–62.
9. Inam M, Altinisik M, Bilgin MD. The effect of quercetin on renal ischemia and reperfusion injury in the rat. Cell Biochem Funct 2002;20:291–6.
10. Huk I, Brovkovych V, Nanobash Vili J, Weigel G, Neumayer C, Partyka L, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study. Br J Surg 1998;85:1080–5.
11. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998;47:224-9.
12. Kim MJ, Lim Y. Protective effect of short-term genistein supplementation on the early stage in diabetes-induced renal damage. Mediators Inflamm 2013;2013:510212.
13. Kamalakkannan N, Stanely Mainzen Prince P. The antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic Clin Pharmacol Toxicol 2006;98:97–103.
14. Kiliari EK, Mullapudi B, Moka PV, Silakabattini K, Nelli G. Inhibition of DPP-IV activity and enhancement of GLP-1expression by aqueous peel extract of punicagranatumin albino wistar rats. Globale Trends Pharm Sci 2014;2:1528-41.
15. Pruden EL, McPherson RA, Fuhrman SA. Clinical guide to laboratory test-Ed. Tiet N. W./Saunders W. B. Company. 3th ed. Section 1: General Clin Test; 1995. p. 268-73.
16. Kaplan A, Urea, Kaplan A. Clin chem the C. V. mosby Co. St louis. Toronto Princeton; 1984. p. 1257-60, 437, 418.
17. Kaplan A. Urea, Kaplan A. Clin chem the C. V. mosby Co. StLouis. Toronto Princeton; 1984. p. 1257-60, 437, 418.
18. Young DS. Effects of disease on clinical lab. Tests, 4th ed., AACC; 2001.
19. Stein EA. Lipids, lipoproteinsand apolipoproteins. In: Tietz NW. ed. Fundamentals of clinical chemistry. 3rd ed. Philadephia: WB Saunders; 1987. p. 448-81.
20. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351.
21. Beutler E, Duron O, Kelly MB. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-90.
22. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.
23. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6.
24. Fossati P, Prencipe L, Berti G. Use of 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin Chem 1980;26:227-31.
25. Bancroft J, Gamble M. Theory and practice of Histological Technique 4th Ed. Churchill Livingston, New York: London, San Francisco, and Tokyo; 2008.
26. SPSS. Statistical package for social science, computer software, Ver. 16. London, UK: SPSS Company; 2008.
27. Duchatelet S, Zucman SC, Laforgue DD, Blanc H, Timsit J, Julier C. FCRL3-169CT functional polymorphism in type 1 diabetes and autoimmunity traits. Biomed Pharmacother 2007;7:62-153.
28. Elsner M, Guldbakke B, Tiedge M, Munday R, Lenzen S. Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin. Diabetologia 2000;43:1328–33.
29. Guex CG, Reginato FZ, de Jesus PR, Brondani JC, Lopes GHH, Bauermann LF. Antidiabetic effects of oleaeuropaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin. J Ethnopharmacol 2019;235:1-7.
30. Cheng D, Liang B, Li Y. Antihyperglycemic effect of ginkgo biloba extract in streptozotocin-induced diabetes in rats. BioMed Res Int 2013;1:1-7.
31. Ewenighi C, Dimkpa U, Onyeanusi J, Onoh L, Onoh G, Ezeugwu U. Estimation of glucose level and body weight in alloxan induced diabetic rat treated with aqueous extract of garcinia kola seed. Ulutas Med J 2015;1:26–30.
32. Al-Enazi MM. Combined therapy of rutin and silymarin has more protective effects on streptozotocin-induced oxidative stress in rats. J Appl Pharm Sci 2014;4:21-8.
33. Chielle EO, Bonfanti G, De Bona KS, Cargnelutti LO, Bitencourt PER, Da Silva PS, et al. Rutin restores adenosine deaminase activity in serum and the liver and improves biochemical parameters in streptozotocin-induced diabetic rats. Rev Bras Plants Med Campinas 2016;18:273-8.
34. Tierney LM, McPhee SJ, Papadakis MA. Current medical diagnosis and treatment. International edition. NewYork: Lange Medical Books/McGraw-Hill; 2002. p. 1203–15.
35. Ran J, Xu G, Ma H, Xu H, Liu Y, Tan R, et al. Febuxostat attenuates renal damage besides exerting hypouricemic effect in streptozotocin-induced diabetic rats. Int J Nephrol 2017;1-9. https://doi.org/10.1155/2017/2739539
36. Jia Q, Yang R, Liu XF, Ma SF, Wang L. Genistein attenuates renal fibrosis in streptozotocin induced diabetic rats. Mol Med Reports 2019;19:423-31.
37. Sattanathan K, Dhanapal CK, Umarani R, Manavalan R. Beneficial effects of rutin on nephropathy: a serious complication associated with diabetes. J Pharm Res 2011;4:3826-8.
38. Muthulingam M. Antidiabetic efficacy of leaf extracts of asteracanihalongifolia (Linn.) nees. onalloxan induced diabetics in male albino wistar rats. Int J Pharm Biomed Res 2010;1:8-34.
39. Ahmed I, Lakhani MS, Gillett M, John A, Raza H. Hypotriglyceridemia and hypo-cholestrolemic effects of antidiabetic momordicacharantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2001;51:155-61.
40. Martin Gallan P, Carrascosa A, Gussinye M, Dominguez C. Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radical Biol Med 2003;34:1563-74.
41. Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress and antioxidants: a review. J Biochem Mol Toxicol 2003;17:24–38.
42. Bekris LM, Shephard C, Peterson M, Hoehna J, Van Yserloo B, Rutledge E, et al. Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset. Autoimmunity 2005;38:567–75.
43. Kamalakkanan N, Rajadurai M, Stanely Mainzen Prince P. Effect of Aeglemarmelos fruits on normal and streptozotocin diabetic wistar rats. J Med Food 2006;6:93–8.
44. Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic ? cell proliferation. Cell 2013;153:747-58.
45. El-Ghandour AH, El-Bendary AS, Shahba AA, Soliman GA. Study of serum betatrophin level in the patients of type 2 diabetes mellitus. Egyptian J Hosp Med 2019;74:1809-16.
46. Abu Farha M, Al-Khairi I, Cherian P. Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D. Lipids Health Dis 2016;15:181.
47. Hu H, Wenjun S, Shuqin Y, Xiafei H. Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients. Diabetes Care 2014;37:2718–22.
48. Tabak AG, Herder C, Rathmann W, Brunner EJ, Kivimaki M. Prediabetes: a high-risk state for diabetes development. Lancet 2012;379:2279–90.
49. Wang L, Jun S, Chuan W. Circulating levels of betatrophin and irisin are not associated with pancreatic ????-cell function in previously diagnosed type 2 diabetes mellitus patients. J Diabetes Res 2016;6:8.
50. Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, et al. Metabolic response to sodiumglucosecotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014;124:499-508.
51. Almalki DA, Alghamdi SA, Al-Attar AM. Comparative study on the influence of some medicinal plants on diabetes induced by streptozotocin in male rats. BioMed Res Int 2019;1-11. https://doi.org/10.1155/2019/3596287