Abstract
Miglitol, an anti-diabetic drug, has been shown to reduce plasma lipids and inhibit free radical generation. The anti-hyperlipidemic and antioxidant effects of miglitol were studied in triton-induced hyperlipidemic rats and high fat diet-fed obese rats. Plasma cholesterol and triglycerides levels were significantly lowered by miglitol at 100 mg/kg body weight doses. Miglitol inhibited generation of superoxide anion and hydroxyl free radicals by 14 and 31 % in enzymatic systems and 19 and 25 % in non-enzymatic systems, respectively. The in-vitro effect of the drug on adipogenesis using 3T3-L1 preadipocytes at 2-, 5- and 10-μM concentrations showed significant inhibition of adipogenesis (34.2 %) at 10-μM concentration. High fat diet-fed rat model was used to investigate anti-hyperlipidemic, anti-obesity and antioxidant effect of miglitol. Miglitol increased the activities of lecithin-cholesterol-acyltransferase (19 %), post heparin lipolytic activity (26 %), lipoprotein lipase (26 %) and triglyceride lipase (31 %) which result in a decrease in plasma lipid levels. The antioxidant enzymes viz., catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and thioredoxin reductase were increased by the drug in the treated animals. The antihyperlipidemic and antioxidant effect of miglitol can be correlated to its effect on different enzymes and it can be used for inhibiting the development of cardiovascular diseases.
Similar content being viewed by others
Abbreviations
- HFD:
-
High fat diet
- LCAT:
-
Lecithin-cholesterol acyltransferase
- PHLA:
-
Post heparin lipolytic activity
- LPL:
-
Lipoprotein lipase
- TGL:
-
Triglyceride lipase
- TC:
-
Total cholesterol
- TG:
-
Triglycerides
- PL:
-
Phospholipids
- HDL:
-
High density lipoprotein
- LDL:
-
Low density lipoprotein
- VLDL:
-
Very low density lipoprotein
- Mig:
-
Miglitol
- CVD:
-
Cardiovascular diseases
- HMG:
-
3-Hydroxy-3-methyl-glutaryl
References
Eckel RH (1997) Obesity and heart disease: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation. 96:3248–3250
Wellman NS, Friedberg B (2002) Causes and consequences of adult obesity: health, social and economic impacts in the United States. Asia Pac J Clin Nutr 11:S705–S709
Bray GA (2000) Overweight, mortality and morbidity. In: Bouchard C (ed) Physical Activity and Obesity. Human Kinetics Publishers Inc, Champaign, IL, pp 31–54
Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113(6):898–918
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114(12):1752–1761
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:685–695
Ohara Y, Peterson TE, Harrison DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91:2546–2551
Kotur-Stevuljevic J, Memon L, Stefanovic A et al (2007) Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients. Clin Biochem 40:181–187
Mahapatra S, Padhiary K, Mishra T, Nayak N, Satpathy M (1998) Study on body mass index, lipid profile and lipid peroxidation status in coronary artery disease. J Indian Med Assoc 96:39–40
Albertini R, Moratti R, De Luca G (2002) Oxidation of low-density lipoprotein in atherosclerosis from basic biochemistry to clinical studies. Curr Mol Med 2:579–592
Matsuura E, Hughes GR, Khamashta MA (2008) Oxidation of LDL and its clinical implication. Autoimmun Rev 7:558–566
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333:1301–1307
Saleem S, Haider S, Naqvi F, Tabassum S, Haleem DJ (2011) Long term administration of HMG-CoA-Reductase inhibitor (simvastatin) affects brain serotonin neurotransmission in male rats. J Basic and Applied Sciences 7(2):79–83
Scott LJ, Spencer CM (2000) Miglitol, A Review of its Therapeutic Potential in Type 2 Diabetes Mellitus. Drugs 59(3):521–549
Johnson AB, Taylor R (1996) Does suppression of postprandial blood glucose excursions by the α-glucosidase inhibitor miglitol improve insulin sensitivity in diet-treated type II diabetic patients? Diabetes Care 19:559–563
Wang N, Minatoguchi S, Chen XH, Hashimoto K, Lu C, Takemura G, Fujiwara H, Uno Y, Arai M (2004) Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart 142(6):983–990
Fujimori K, Amano F (2011) Niacin promotes adipogenesis by reducing production of anti-adipogenic PGF2α through suppression of C/EBPβ-activated COX-2 expression. Prostaglandins Other Lipid Mediat 94(3–4):96–103
Flora SJS (2009) Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2(4):191–206
Kumar V, Khan MM, Khanna AK, Singh R, Singh S, Chander R, Mahdi F, Mahdi AA, Saxena JK, Singh RK (2008) Hypolipidemic activity of Anthocephalus indicus (kadam) in hyperlipidemic rats. Med Chem Res 17:152–158
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol. Methods 65:55–63
Swarnkar G, Sharan K, Siddiqui JA, Chakravarti B, Rawat P, Kumar M, Arya KR, Maurya R, Chattopadhyay N (2011) A novel flavonoid isolated from the stem-bark of Ulmus wallichiana Planchon stimulates osteoblast function and inhibits osteoclast and adipocyte differentiation. Eur J Pharmacol 658(2–3):65–73
Khanna AK, Rizivi F, Chander R (2002) Lipid lowering activity of Phyllanthus niruri in hyperlipidemic rats. J Ethnopharmacol 82(1):19–32
Parekh AC, Jung DH (1970) Cholesterol estimation with ferric acetate-uranium acetate and sulfuric acid, ferrous sulfate reagents. Anal Chem 42:1423–1427
Rice LB (1970) Determination of triglycerides (enzymatic method). Clin Chem 31(5):746–750
Kallner A (1975) Determination of phosphate in serum and urine by a single step malachite green method. Clin Chem Acta 59:35–39
Mosinger F (1965) Photometric adaptation of Doli’s micromethod for determination of free fatty acid. J Lipid Res 6:157–160
Burstein RF, Scholnick VS (1972) Biochemistry and methodology of lipids. J Lipid Res 25:375–382
Mandukhail SR, Aziz N, Gilani AH (2010) Studies on antidyslipidemic effect of Morinda citrifolia (Noni) fruits, leaves and root extracts. Lipids in Health and Disease 9:88–93
Nagasaki T, Akanuma Y (1977) A new colorimetric method for determination of plasma Lecithin-cholesterol acyltransferase activity. Clin Chem Acta 75:371–375
Wing DR, Robinson DS (1968) Clearing factor lipase in adipose tissue. Biochem J 109:841–849
Mays PA, Felts JM (1968) The functional status of lipoprotein lipase in rat liver. Biochem J 108:483–487
Mossback EH, Klenisky HJ, Hall P, Kendall EE (1954) Determination of deoxycholic and cholic acid in bile. Arch Biochem Biophys 51:402–409
Shrivastava A, Chaturvedi U, Sonkar R, Khanna AK, Saxena JK, Bhatia G (2012) Antioxidant effect of Azadirachta indica on high fat diet induced diabetic Charles foster rats. Appl Biochem Biotechnol 167:229–236
Okhawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Analytical biochemistry 95:351–358
Yen GH, Chen HY (1995) Antioxidant activity of various tea extracts in relation to their anti-mutagenicity. J Agric Food Chem 43:27–32
Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Ind J Biochem Biophys 21:130–132
Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394
Rotruck JT, Pope AL, Ganther HE, Swason AB (1973) Selenium: Biochemical role as a component of glutathione peroxidase. Science 178:588–590
Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490
Kapoor G, Banyal HS (2011) Purification and Characterization of Plasmodium berghei Thioredoxin Reductase. Asian Journal of Animal Sciences 5:145–152
Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25:29–38
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809
Mirjana B (2007) Pathogenetic aspects of atherosclerosis. Acta Med Medianae 46:25–29
Howard BV, Ruotolo G, Robbins DC (2003) Obesity and dyslipidemia. Endocrinol Metab Clin N Am 32:855–867
Spiegelman BM, Choy L, Hotamisligil GS, Graves RA, Tontonoz P (1993) Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes. J Biol Chem 268:6823–6826
Shrivastava A, Chaturvedi U, Sonkar R, Khanna AK, Saxena JK, Bhatia G (2011) Antidyslipidemic, Antiatherogenic and Antioxidant Activity of Allium Sativum in Charles Foster Rats. IJCPR 2(2):110–119
Kuroda M, Tanzawa K, Tsujita Y, Endo A (1977) Mechanism for elevation of hepatic cholesterol synthesis and serum cholesterol levels in Triton WR-1339 induced hyperlipidemia. Biochem Biophys Acta 489(1):119–125
Schotz MC, Seanu A, Page IH (1957) Effect of triton on lipoprotein lipase of rat plasma. Am J Physiol 188(2):399–402
Hayashi T, Ishikawa T, Naito M, Kuzuya M, Funaki C, Asai K, Hidaka H, Kuzuya F (1991) Low level hyperlipidemia impairs endothelium-dependant relaxation of porcine coronary arteries by two mediators. Atherosclerosis 87(1):23–28
Nigris F, Lerman A, Ignarro LJ, Williams-Ignarro S, Sica V, Baker AH, Lerman LO, Geng YJ, Napoli C (2003) Oxidation sensitive mechanisms, vascular apoptosis and atherosclerosis. Trends Mol Med 9(8):351–359
Javitt NB (December 1994) Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. FASEB J 8(15):1308–1311
Applebaum DM, Goldberg AP, Pykälistö OJ, Brunzell JD, Hazzard WR (1977) Effect of estrogen on post-heparin lipolytic activity. Selective decline in hepatic triglyceride lipase. J Clin Invest 59(4):601–608
Busserolles J, Gueux E, Rock E, Demigne C, Mazur A, Rayssiguier Y (2003) Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. Journal of Nutrition 133:1903–1908
Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ (1996) Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347:781–786
Janero R (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Rad Biol Med 9:515–540
Acknowledgments
All the work was supported by the Council of Scientific and Industrial Research, New Delhi (India). CDRI Communication No.: 8376.
Conflict of interest
There is no conflict of interest among authors.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Shrivastava, A., Chaturvedi, U., Singh, S.V. et al. Lipid Lowering and Antioxidant Effect of Miglitol in Triton Treated Hyperlipidemic and High Fat Diet Induced Obese Rats. Lipids 48, 597–607 (2013). https://doi.org/10.1007/s11745-012-3753-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-012-3753-3