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Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism

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Abstract

Objectives: Reactive oxygen species (ROS) have been implicated in the development of streptozotocin (STZ)-induced diabetes mellitus. Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is an antioxidant. An investigation was made of the effects of SDG on the development of STZ-induced diabetes in rat, to determine if SDG can prevent/reduce the development of diabetes and if this prevention/reduction is associated with reduction in oxidative stress.

Design and Methods: The rats were divided into 4 groups: Group I, Control; Group II, SDG (22 mg/kg body wt, orally) for 24 days; Group III, STZ (80 mg/kg intraperitoneally); Group IV, SDG in the dose similar to Group II three days prior to STZ and 21 days thereafter. Oxidative stress was assessed by measuring serum and pancreatic lipid peroxidation product malondialdehyde (MDA), pancreatic antioxidant reserve (pancreatic-CL) and oxygen free radical producing activity of white blood cells (WBC-CL). A diagnosis of diabetes was made on the basis of glucosuria and was confirmed at the time of sacrifice (21 days after STZ treatment) by the presence of hyperglycemia. At the end of the protocol blood samples were collected for estimation of glucose, MDA and WBC-CL, and pancreas were removed for estimation of MDA and antioxidant reserve.

Results: Incidence of diabetes was 100% in Group III and 25% in Group IV. SDG prevented the development of diabetes by 75%. Development of diabetes was associated with an increase in serum and pancreatic MDA, and in WBC-CL, and a decrease in pancreatic antioxidant reserve. Prevention of diabetes by SDG was associated with a decrease in serum and pancreatic MDA and WBC-CL and an increase in pancreatic antioxidant reserve.

Conclusions: These results suggest that STZ-induced diabetes is mediated through oxidative stress and that SDG is effective in reducing the STZ-induced diabetes mellitus.

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References

  1. Nerup J: HLA studies in diabetes mellitus. A review. Adv Metab Disord 9: 263-273, 1978

    Google Scholar 

  2. Rayfield EJ, Keely KJ, Yoon JW: Rubella virus-induced diabetes in hamster. Diabetes 35: 1276-1281, 1986

    Google Scholar 

  3. Ginsberg-Fellener F, Witt ME, Yagihashi S, Dobersen MJ, Taub F, Fedun B, McCoy RC, Roman SH, Davies TF, Cooper LZ, Rubenstein P, Notteins A: Congenital rubella syndrome as a model for Type I (Insulin-dependent) diabetes mellitus: Increased prevalance of islet cell surface antibodies. Diabetologia 27: 87-89, 1984

    Google Scholar 

  4. Rabinovitch A, Suarez WL, Thomas PD, Strynadka K, Simpson I: Cytotoxic effects of cytokines on rat islets: Evidence for involvement of free radicals and lipid peroxidation. Diabetologia 35: 409-413, 1992

    Google Scholar 

  5. Dulin WE, Soret MG: Chemically and hormonally induced diabetes. In: M.E. Volk, K.F. Wellman (eds). The Diabetic Pancreas. Plenum Press, New York, 1997, pp 425-465

    Google Scholar 

  6. Junod A, Lambert AE, Orci L, Pictet R, Gonent AE, Renold AE: Studies of the diabetogenic action of streptozotocin. Proc Soc Expt Biol Med 126: 201-205, 1967

    Google Scholar 

  7. Barbosa J, Bach FH: Cell mediated autoimmunity in Type I diabetes. Diabetes Metab Rev 3: 981-1004, 1987

    Google Scholar 

  8. Baynes JW: Perspectives in diabetes: role of oxidative stress in development of complications in diabetes. Diabetes 40: 405-412, 1991

    Google Scholar 

  9. Berton G, Zeni L, Cassatella MA, Rossi F: Gamma interferon is able to enhance the oxidative metabolism of human neutrophils. Biochem Biophys Res Commun 138: 1276-1282, 1986

    Google Scholar 

  10. Braquet P, Hosfard D, Braquet M, Bourgain R, Bussolino F: Role of cytokines and platelet activating factor in microvascular injury. Int Arch Allerg Appl Immunol 88: 88-100, 1989

    Google Scholar 

  11. Charlton BA, Bacelj A, Mandel TE: Administration of silica particles or anti Lyt 2 antibody prevents beta-cell destruction in NOD mice given cyclophosphamide. Diabetes 37: 930-935, 1988

    Google Scholar 

  12. Nathan CF, Tsunawaki S: Secretion of toxic oxygen products by macrophages: Regulatory cytokines and their effect on the oxidase. Ciba Foundation Symposium 118: 211-230, 1986

    Google Scholar 

  13. Paubert-Braquet M, Longchamps MA, Kolz P: Tumor necrosis factor (TNF) primes human neutrophil (PMN) platelet-activating factor (PAF)-induced superoxide generation. Consequences in promoting PMN-mediated endothelial cell (EC) damages. Abstract Prostaglandins 35: 803, 1988

    Google Scholar 

  14. Freeman BA, Crapo JD: Biology of disease. Free radicals and tissue injury. Lab Invest 47: 412-426, 1982

    Google Scholar 

  15. Meerson FZ, Kagan VE, Kozlov YP, Belkina LM, Arkhipenko YV: The role of lipid peroxidation in pathogenesis of ischemic damage and antioxidant protection of the heart. Basic Res Cardiol 77: 465-468, 1982

    Google Scholar 

  16. Sumoski W, Baquerizo H, Rabinovitch A: Oxygen radical scavengers protect rat islet cells from damage by cytokines. Diabetologia 32: 792-796, 1989

    Google Scholar 

  17. Grankvist K, Marklund S, Sehlin J, Teljedal DB: Superoxide dismutase, catalase and scavengers of hydroxyl radicals protect against the toxic action of alloxan on pancreatic islet cells in vitro. J Biochem 182: 17-25, 1979

    Google Scholar 

  18. Fischer LJ, Hamburger SA: Dimethylthiourea: a radical scavenger that protects isolated pancreatic islets from the effects of alloxan and dihydroxyfumarate exposure. Life Sci 26: 1405-1409, 1980

    Google Scholar 

  19. Tibaldi J, Benjamin J, Cabbat FS, Heikkila RE: Protection against alloxan-induced diabetes by various urea derivatives, relationship between protective effects and reactivity with hydroxyl radical. J Pharmacol Exptl Therap 211: 411-418, 1979

    Google Scholar 

  20. Like AA, Rossini A: Streptozotocin-induced pancreatic insulitis: New model of diabetes mellitus. Science 193: 415-417, 1976

    Google Scholar 

  21. Robins MJ, Sharp RA, Slonim AE, Burr IM: Protection against streptozotocin-induced diabetes by superoxide dismutase. Diabetologia 18: 55-58, 1980

    Google Scholar 

  22. Wilson JL, Patton NJ, McCord JM, Mullins DW, Mossman BT: Mechanism of streptozotocin and alloxan-induced damage in rat B cells. Diabetologia 27: 587-591, 1984

    Google Scholar 

  23. Bakke JE, Klosterman HJ: A new diglucoside from flaxseed. Proc North Dakota Acad Sci 10: 18-22, 1956

    Google Scholar 

  24. Cox CP, Wood KL: Selective antagonism of platelet-activating factor (PAF)-induced aggregation and secretion of washed rabbit platelets by CV-3988, L-652731, triazolam and alphazolam. Thromb Res 47: 249-257, 1987

    Google Scholar 

  25. Westcott ND, Muir AD: Process for extracting lignans from flaxseed. United States Patent No. 5705618, Jan. 6, 1998

  26. Prasad K: Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flaxseed. Mol Cell Biochem 168: 117-123, 1997

    Google Scholar 

  27. Kakkar R, Mantha SV, Radhi J, Prasad K, Kalra J: Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin Sci 94: 623-632, 1998

    Google Scholar 

  28. Kapoor R, Prasad K: Role of oxyradicals in cardiovascular depression and cellular injury in hemorrhagic shock and re-infusion: Effect of SOD and catalase. Circ Shock 43: 79-94, 1994

    Google Scholar 

  29. Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95: 351-358, 1979

    Google Scholar 

  30. Prasad K, Gupta JB, Kalra J, Lee P, Mantha SV, Bharadwaj B: Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model. J Mol Cell Cardiol 28: 375-385, 1996

    Google Scholar 

  31. Prasad K, Kalra J, Lee P: Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: Effects of Probucol. Int J Angiol 3: 100-112, 1994

    Google Scholar 

  32. Prasad K: Dietary flaxseed in the prevention of hypercholesterolemic atherosclerosis. Atherosclerosis 132: 69-76, 1997

    Google Scholar 

  33. Prasad K, Kalra J, Chaudhary AK, Debnath D: Effects of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters. Am Heart J 119: 538-550, 1990

    Google Scholar 

  34. Cornall AG, Bardwill CJ, David MM: Determination of serum proteins by means of biuret reaction. J Biol Chem 177: 751-756, 1949

    Google Scholar 

  35. Kadish AH, Little RL, Sternberg JC: A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption. Clin Chem 14: 116-131, 1968

    Google Scholar 

  36. Kakkar R, Kalra J, Mantha SV, Prasad K: Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem 151: 113-119, 1995

    Google Scholar 

  37. Sato Y, Hotta N, Sakamoto N: Lipid peroxide level in plasma of diabetic patients. Biochem Med 25: 373-378, 1981

    Google Scholar 

  38. Hunt JV, Smith CCT, Wolff SP: Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes 39: 1420-1424, 1990

    Google Scholar 

  39. Wolff SP, Dean RT: Glucose autoxidation and protein modification: the potential role of autoxidative glycosylation in diabetes. J Biochem 245: 243-250, 1987

    Google Scholar 

  40. Hussain MJ, Peakman M, Gallati H, Lo SSS, Hawa M, Viberti GC, Watkins PJ, Leslie RDG, Vergani D: Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetologia 39: 60-69, 1996

    Google Scholar 

  41. Wautier JL, Wautier MP, Schmidt AM, Anderson GM, Hori O, Zoukourian C, Capron L, Chappey O, Yan S-D, Brett J, Guillausseau PJ, Stern D: Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to vessel wall via a specific receptor inducing oxidant stress in vasculature: a link between surface associated AGEs and diabetic complications. Proc Natl Acad Sci USA 91: 7742-7746, 1994

    Google Scholar 

  42. Ohkawa T, Sato Y, Naoi M: Hydroxyl radical formation in diabetic rats induced by streptozotocin. Life Sci 56: 1789-1798, 1995

    Google Scholar 

  43. Asayama K, English D, Slonim AE, Buer IM: Chemiluminescence as an index of drug induced free radical production in pancreatic islets. Diabetes 33: 160-163, 1984

    Google Scholar 

  44. Takasu N, Komiya I, Asasa T, Nagasawa Y, Yamada T: Streptozotocin and alloxan induced H2O2 generation and DNA fragmentation in pancreatic islets. Diabetes 40: 1141-1145, 1991

    Google Scholar 

  45. Cadenas E, Sies H: Low level chemiluminescence of liver microsomal fractions initiated by tert-butyl hydroperoxide: relation to microsomal hemoproteins, oxygen dependence, and lipid peroxidation. Eur J Biochem 124: 349-356, 1982

    Google Scholar 

  46. Cadenas E, Varsavsky AI, Boveris A, Chance B: Oxygen or organic hydroperoxide-induced chemiluminescence of brain and liver homogenates. J Biochem 198: 645-654, 1981

    Google Scholar 

  47. Cadenas E, Wefers H, Sies H: Low level chemiluminescence of isolated hepatocytes. Eur J Biochem 119: 531-536, 1981

    Google Scholar 

  48. Shingu M, Nobunga M: Chemotactic activity generated in human serum from 5th component complement by hydrogen peroxide. J. Pathol 117: 201-206, 1984

    Google Scholar 

  49. Webster KO, Hong SR, Johnston JB Jr, Henson PM: Biological effects of the human complement fragments C5a and C5ades Arg on neutrophil function. Immunopharmacology 2: 201-219, 1980

    Google Scholar 

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Prasad, K., Mantha, S., Muir, A. et al. Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism. Mol Cell Biochem 206, 141–150 (2000). https://doi.org/10.1023/A:1007018030524

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