Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly ( ) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40？mg/kg？b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats. 1. Introduction Diabetes mellitus (DM) is a series of endocrine metabolic disorders characterized by increased fasting and postprandial glucose levels as well as an insulin deficiency and/or defects of insulin action on regulation of glucose. More than 300 million people are expected to suffer from diabetes during the year 2025, and the global cost of managing diabetes and its various complications almost reaches one trillion US dollar annually as per worldwide projected epidemiology data [1, 2]. Reactive oxygen species (ROS) play a crucial role in the pathogenesis of some serious diseases/disorders, such as cancer, liver cirrhosis, cardiovascular diseases, diabetes, and inflammation associated malfunction [3]. These effects especially increased production of free radicals and its effect during diabetes are devastating and well documented [4, 5]. Streptozotocin (STZ) is frequently used to induce diabetes mellitus in experimental animal systems, and its toxic effects are produced by nitric oxide on pancreatic -cells. The cytotoxic action of STZ is associated with the generation of ROS causing oxidative tissue damage [6]. Oxidative stress has been reported to play an essential role in diabetes right from its genesis to the development of microvascular and macrovascular
References
[1]
A. K. Oglesby, K. Secnik, J. Barron, I. Al-Zakwani, and M. J. Lage, “The association between diabetes related medical costs and glycemic control: a retrospective analysis,” Cost Effectiveness and Resource Allocation, vol. 4, article 1, 2006.
[2]
D. R. Whiting, L. Guariguata, C. Weil, and J. Shaw, “IDF Diabetes Atlas: global estimates of the prevalence of diabetes for 2011 and 2030,” Diabetes Research and Clinical Practice, vol. 94, no. 3, pp. 311–321, 2011.
[3]
B. Halliwell, “Free radicals and antioxidants: updating a personal view,” Nutrition Reviews, vol. 70, no. 5, pp. 257–265, 2012.
[4]
I. Afanas'Ev, “Signaling of reactive oxygen and nitrogen species in diabetes mellitus,” Oxidative Medicine and Cellular Longevity, vol. 3, no. 6, pp. 361–373, 2010.
[5]
W. Dr？ge, “Free radicals in the physiological control of cell function,” Physiological Reviews, vol. 82, no. 1, pp. 47–95, 2002.
[6]
T. Szkudelski, “The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas,” Physiological Research, vol. 50, no. 6, pp. 537–546, 2001.
[7]
H. Raza, S. K. Prabu, A. John, and N. G. Avadhani, “Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats,” International Journal of Molecular Sciences, vol. 12, no. 5, pp. 3133–3147, 2011.
[8]
W. Wei, Q. Liu, Y. Tan, L. Liu, X. Li, and L. Cai, “Oxidative stress, diabetes, and diabetic complications,” Hemoglobin, vol. 33, no. 5, pp. 370–377, 2009.
[9]
R. Rahimi, S. Nikfar, B. Larijani, and M. Abdollahi, “A review on the role of antioxidants in the management of diabetes and its complications,” Biomedicine and Pharmacotherapy, vol. 59, no. 7, pp. 365–373, 2005.
[10]
P. Arulselvan, G. P. Senthilkumar, D. S. Kumar, and S. Subramanian, “Anti-diabetic effect of Murraya koenigii leaves on streptozotocin induced diabetic rats,” Pharmazie, vol. 61, no. 10, pp. 874–877, 2006.
[11]
H.-Y. Hung, K. Qian, S. L. Morris-Natschke, C.-S. Hsu, and K.-H. Lee, “Recent discovery of plant-derived anti-diabetic natural products,” Natural Product Reports, vol. 29, no. 5, pp. 580–606, 2012.
[12]
G. P. S. Kumar, P. Arulselvan, D. S. Kumar, and S. P. Subramanian, “Anti-diabetic activity of fruits of Terminalia chebula on streptozotocin induced diabetic rats,” Journal of Health Science, vol. 52, no. 3, pp. 283–291, 2006.
[13]
S. Subramanian and P. Arulselvan, “Evaluation of hypolipidemic properties of Murraya koenigii leaves studied in streptozotocin induced diabetic rats,” Biomedicine, vol. 29, no. 3, pp. 220–225, 2009.
[14]
WHO, “Expert committee on diabetes mellitus,” Tech. Rep. 646, World Health Organization, Geneva, USA, 1980.
[15]
P. Arulselvan and S. P. Subramanian, “Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic β-cells in experimental diabetes in rats,” Chemico-Biological Interactions, vol. 165, no. 2, pp. 155–164, 2007.
[16]
P. Arulselvan and S. Subramanian, “Effect of Murraya koenigii leaf extract on carbohydrate metabolism studied in streptozotocin induced diabetic rats,” International Journal of Biological Chemistry, vol. 1, pp. 21–28, 2007.
[17]
M. Power and R. Pratley, “Alternative and complementary treatments for metabolic syndrome,” Current Diabetes Reports, vol. 11, no. 3, pp. 173–178, 2011.
[18]
M. Yoshikawa, Y. Pongpiriyadacha, A. Kishi et al., “Biological activities of Salacia chinensis originating in Thailand: the quality evaluation guided by α-glucosidase inhibitory activity,” Yakugaku Zasshi, vol. 123, no. 10, pp. 871–880, 2003.
[19]
P. S. Sellamuthu, B. P. Muniappan, S. M. Perumal, and M. Kandasamy, “Antihyperglycemic effect of mangiferin in streptozotocin induced diabetic rats,” Journal of Health Science, vol. 55, no. 2, pp. 206–214, 2009.
[20]
S. Periyar Selvam, P. Arulselvan, P. M. Balu, and K. Murugesan, “Effect of mangiferin isolated from Salacia chinensis regulates the kidney carbohydrate metabolism in streptozotocin-induced diabetic rats,” Asian Pacific Journal of Tropical Biomedicine, vol. 2, pp. S1583–S1587, 2012.
[21]
X. J. Li, Z. C. Du, Y. Huang, et al., “Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin,” Chinese Journal Natural Medicine, vol. 11, pp. 296–301, 2013.
[22]
P. S. Sellamuthu, P. Arulselvan, B. P. Muniappan, S. Fakurazi, and M. Kandasamy, “Influence of mangiferin on membrane bound phosphatases and lysosomal hydrolases in streptozotocin induced diabetic rats,” Latin American Journal of Pharmacy, vol. 31, no. 7, pp. 1013–1020, 2012.
[23]
S. Guha, S. Ghosal, and U. Chattopadhyay, “Antitumor, immunomodulatory and anti-HIV effect of mangiferin, a naturally occurring glucosylxanthone,” Chemotherapy, vol. 42, no. 6, pp. 443–445, 1996.
[24]
C. Yoosook, N. Bunyapraphatsara, Y. Boonyakiat, and C. Kantasuk, “Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants,” Phytomedicine, vol. 6, no. 6, pp. 411–419, 2000.
[25]
J. Leiro, J. A. Arranz, M. Yá？ez, F. M. Ubeira, M. L. Sanmartín, and F. Orallo, “Expression profiles of genes involved in the mouse nuclear factor-kappa B signal transduction pathway are modulated by mangiferin,” International Immunopharmacology, vol. 4, no. 6, pp. 763–778, 2004.
[26]
I. Stoilova, S. Gargova, A. Stoyanova, and L. Ho, “Antimicrobial and antioxidant activity of the polyphenol mangiferin,” Herba Polonica Journal, vol. 51, pp. 37–44, 2005.
[27]
M. R. Campos-Esparza, M. V. Sánchez-Gómez, and C. Matute, “Molecular mechanisms of neuroprotection by two natural antioxidant polyphenols,” Cell Calcium, vol. 45, no. 4, pp. 358–368, 2009.
[28]
T. Sasaki, S. Matsy, and A. Somae, “Effect of acetic acid concentration on the colour reaction in the O-toluidine boric acid method for blood glucose estimation,” Rinsho Kagaku, vol. 1, pp. 346–353, 1972.
[29]
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, “Protein measurement with the Folin phenol reagent,” The Journal of Biological Chemistry, vol. 193, no. 1, pp. 265–275, 1951.
[30]
H. Ohkawa, N. Ohishi, and K. Yagi, “Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction,” Analytical Biochemistry, vol. 95, no. 2, pp. 351–358, 1979.
[31]
Z.-Y. Jiang, J. V. Hunt, and S. P. Wolff, “Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein,” Analytical Biochemistry, vol. 202, no. 2, pp. 384–389, 1992.
[32]
J. Sedlak and R. H. Lindsay, “Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent,” Analytical Biochemistry, vol. 25, pp. 192–205, 1968.
[33]
H. P. Misra and I. Fridovich, “The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase,” Journal of Biological Chemistry, vol. 247, no. 10, pp. 3170–3175, 1972.
[34]
J. T. Rotruck, A. L. Pope, H. E. Ganther, A. B. Swanson, D. G. Hafeman, and W. G. Hoekstra, “Selenium: biochemical role as a component of glatathione peroxidase,” Science, vol. 179, no. 4073, pp. 588–590, 1973.
[35]
S. Takahara, H. B. Hamilton, J. V. Nell, T. Y. Kobra, Y. Ogura, and E. T. Nishimura, “Hypocatalasemia: a new genetic carrier state,” The Journal of Clinical Investigation, vol. 39, pp. 610–619, 1960.
[36]
H. Yang, X. Jin, C. W. K. Lam, and S.-K. Yan, “Oxidative stress and diabetes mellitus,” Clinical Chemistry and Laboratory Medicine, vol. 49, no. 11, pp. 1773–1782, 2011.
[37]
X. Wang and C. X. Hai, “ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus: is Nrf2 a potential target for the treatment?” Mini-Reviews in Medicinal Chemistry, vol. 11, no. 12, pp. 1082–1092, 2011.
[38]
T. Matsunami, Y. Sato, Y. Hasegawa et al., “Enhancement of reactive oxygen species and induction of apoptosis in streptozotocin-induced diabetic rats under hyperbaric oxygen exposure,” International Journal of Clinical and Experimental Pathology, vol. 4, no. 3, pp. 255–266, 2011.
[39]
P. Manna, J. Ghosh, J. Das, and P. C. Sil, “Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: protective role of arjunolic acid,” Toxicology and Applied Pharmacology, vol. 244, no. 2, pp. 114–129, 2010.
[40]
P. Arulselvan and S. Subramanian, “Ultrastructural and biochemical abnormalities in the liver of streptozotocin-diabetic rats: protective effects of Murraya koenigii,” Journal of Pharmacology and Toxicology, vol. 3, no. 3, pp. 190–202, 2008.
[41]
A. E. Holley and K. H. Cheeseman, “Measuring free radical reactions in vivo,” British Medical Bulletin, vol. 49, no. 3, pp. 494–505, 1993.
[42]
B. Matkovics, M. Kotorman, I. S. Varga, D. Quy Hai, and C. Varga, “Oxidative stress in experimental diabetes induced by streptozotocin,” Acta Physiologica Hungarica, vol. 85, no. 1, pp. 29–38, 1998.
[43]
J. W. Baynes and S. R. Thorpe, “Role of oxidative stress in diabetic complications: a new perspective on an old paradigm,” Diabetes, vol. 48, no. 1, pp. 1–9, 1999.
[44]
N. Rathore, M. Kale, S. John, and D. Bhatnagar, “Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat erythrocytes,” Indian Journal of Physiology and Pharmacology, vol. 44, no. 2, pp. 161–166, 2000.
[45]
S. Srinivasan and L. Pari, “Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats,” Chemico-Biological Interactions, vol. 195, no. 1, pp. 43–51, 2012.
[46]
E. O. Omotayo, S. Gurtu, S. A. Sulaiman, M. S. A. Wahab, K. N. S. Sirajudeen, and M. S. M. Salleh, “Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats,” International Journal for Vitamin and Nutrition Research, vol. 80, no. 1, pp. 74–82, 2010.
[47]
E. Y. S？zmen, B. S？zmen, Y. Delen, and T. Onat, “Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may implicate poor glycemic control,” Archives of Medical Research, vol. 32, no. 4, pp. 283–287, 2001.
[48]
A. A. R. Sayed, M. Khalifa, and F. F. Abd el-Latif, “Fenugreek attenuation of diabetic nephropathy in alloxan-diabetic rats—attenuation of diabetic nephropathy in rats,” Journal of Physiology and Biochemistry, vol. 68, no. 2, pp. 263–269, 2012.
[49]
M. Lorenzi, “The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient,” Experimental Diabesity Research, vol. 2007, Article ID 61038, 10 pages, 2007.
[50]
K. Ravi, B. Ramachandran, and S. Subramanian, “Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin-induced diabetic rats,” Biological and Pharmaceutical Bulletin, vol. 27, no. 8, pp. 1212–1217, 2004.
[51]
A. Prathapan, S. V. Nampoothiri, S. Mini, and K. G. Raghu, “Antioxidant, antiglycation and inhibitory potential of Saraca ashoka flowers against the enzymes linked to type 2 diabetes and LDL oxidation,” European Review for Medical and Pharmacological Sciences, vol. 16, no. 1, pp. 57–65, 2012.
[52]
N. L. Parinandi, E. W. Thompson, and H. H. O. Schmid, “Diabetic heart and kidney exhibit increased resistance to lipid peroxidation,” Biochimica et Biophysica Acta, vol. 1047, no. 1, pp. 63–69, 1990.
