RSS-Feed abonnieren
DOI: 10.1055/s-0031-1296194
Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats
Publikationsverlauf
Publikationsdatum:
27. November 2011 (online)
![](https://www.thieme-connect.de/media/amf/201104/lookinside/thumbnails/10.1055-s-0031-1296194-1.jpg)
Abstract
The present study was designed to examine whether astaxanthin (ASX, 3,3-dihydroxybeta, beta-carotene-4,4-dione, CAS 472-61-7), a dietary antioxidant carotenoid that is naturally present in algae, crustaceans, and fish, has a protective effect on endothelial dysfunction of aortas in diabetic rats and the possible molecular mechanism involved. Male Wistar rats were randomly divided into four groups: control rats, diabetic rats, diabetic rats treated with ASX (10 mg/kg/d), and control rats treated with ASX. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). STZ-induced diabetes in rats was complicated with excessive oxidative stress and endothelial dysfunction, increased serum oxidized low-density lipoprotein (ox-LDL) and aortic malondialdehyde (MDA) levels, inhibited endothelium-dependent vasorelaxation to acetylcholine (ACh) and unaffected endothelium-dependent vasorelaxation to sodium nitroprusside (SNP). Simultaneously, lectin-like oxLDL receptor-1 (LOX-1) expression was enhanced and endothelial nitric oxide (NO) synthase (eNOS) expression was reduced in the aortas of diabetic rats. ASX treatment could significantly decrease serum oxLDL and aortic MDA levels, attenuate blunted endothelium-dependent vasodilator responses to ACh, upregulate eNOS expression, and decrease LOX-1 expression. These results indicated that ASX could ameliorate diabetic endothelial dysfunction by inhibiting the ox-LDL-LOX-1-eNOS pathway. Treatment with ASX might be clinically useful for diabetic complications associated with endothelial dysfunction.
-
References
- 1 Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP et al. Diabetes and mortality following acute coronary syndromes. JAMA. 2007; 298: 765-75
- 2 Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004; 141: 421-431
- 3 Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000; 87: 840-4
- 4 Zhang C, Yang J, Jennings LK. Leukocyte-derived myeloperoxidase amplifies high-glucose-induced endothelial dysfunction through interaction with high-glucose-stimulated, vascular non-leukocyte-derived reactive oxygen species. Diabetes. 2004; 53: 2950-9
- 5 Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y et al. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997; 386: 73-7
- 6 Chen M, Nagase M, Fujita T, Narumiya S, Masaki T, Sawamura T. Diabetes enhanches lectin-like oxidized LDL receptor-1 (LOX-1) expression in the vascular endothelium: possible role of LOX-1 ligand and AGE. Biochem Biophys Res Commun. 2001; 287: 962-8
- 7 Li L, Sawamura T, Renier G. Glucose enhances endothelial LOX-1 expression:Role of LOX-1 in glucose-induced human monocyte adhesion to endothelium. Diabetes. 2003; 52: 1843-50
- 8 Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants:a review. J Biochem Mol Toxicol. 2003; 17: 24-38
- 9 Wang LJ, Yu YH, Zhang LG, Wang Y, Niu N, Li Q et al. Taurine rescues vascular endothelial dysfunction in streptozocin-induced diabetic rats: correlated with downregulation of LOX-1 and ICAM-1 expression on aortas. Eur J Pharmacol. 2008; 597: 75-80
- 10 Jono T, Miyazaki A, Nagai R, Sawamura T, Kitamura T, Horiuchi S. Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) serves as an endothelial receptor for advanced glycation end products (AGE). FEBS Lett. 2002; 511: 170-4
- 11 Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res. 2006; 69: 36-45
- 12 Chavakis E, Dernbach E, Hermann C, Mondorf UF, Zeiher AM, Dimmeler S. Oxidized LDL inhibits vascular endothelial growth factor-induced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxide synthase pathway. Circulation. 2001; 103: 2102-7
- 13 Xu X, Gao X, Potter BJ, Cao JM, Zhang C. Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice. Arterioscler Thromb Vasc Biol. 2007; 27: 871-7
- 14 Wang C, Li J, Lv X, Zhang M, Song Y, Chen L et al. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol. 2009; 620: 131-7
- 15 Rask-Madsen C, King GL. Mechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract Endocrinol Metab. 2007; 3: 46-56
- 16 Cominacini L, Pasini AF, Garbin U. Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species. J Biol Chem. 2000; 275: 12633-8
- 17 Rao AV, Rao LG. Carotenoids and human health. Pharmacol Res. 2007; 55: 207-16
- 18 Fassett RG, Coombes JS. Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol. 2009; 5: 333-42
- 19 Naguib YM. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000; 48: 1150-4
- 20 Shen H, Kuo CC, Chou J, Delvolve A, Jackson SN, Post J et al. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J. 2009; 23: 1958-68
- 21 Chew BP, Park JS, Wong MW, Wong TS. A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res. 1999; 19: 1849-53
- 22 Ohgami K, Shiratori K, Kotake S, Nishida T, Mizuki N, Yazawa K et al. Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest Ophthalmol Vis Sci. 2003; 44: 2694-701
- 23 Kurihara H, Koda H, Asami S, Kiso Y, Tanaka T. Contribution of the antioxidative property of astaxanthin to its protective effect on the promotion of cancer metastasis in mice treated with restraint stress. Life Sci. 2002; 70: 2509-20
- 24 Yoshida H, Yanai H, Ito K, Tomono Y, Koikeda T, Tsukahara H et al. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. Atherosclerosis. 2010; 209: 520-3
- 25 Uchiyama K, Naito Y, Hasegawa G, Nakamura N, Takahashi J, Yoshikawa T. Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002; 7: 290-3
- 26 Naito Y, Uchiyama K, Mizushima K, Kuroda M, Akagiri S, Takagi T et al. Microarray profiling of gene expression patterns in glomerular cells of astaxanthin-treated diabetic mice: a nutrigenomic approach. Int J Mol Med. 2006; 18: 685-95
- 27 Nakano M, Onodera A, Saito E, Tanabe M, Yajima K, Takahashi J et al. Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats. J Nutr Sci Vitaminol (Tokyo). 2008; 54: 329-34
- 28 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Bio-chem. 1979; 95: 351-8
- 29 Cheng X, Cheng XS, Kuo KH, Pang CC. Inhibition of iNOS augments cardiovascular action of noradrenaline in streptozotocin-induced diabetes. Cardiovasc Res. 2004; 64: 298-307
- 30 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25: 402-8
- 31 Nakano M, Orimo N, Katagiri N, Tsubata M, Takahashi J, Van Chuyen N. Inhibitory effect of astraxanthin combined with Flavangenol on oxidative stress biomarkers in streptozotocin-induced diabetic rats. Int J Vitam Nutr Res. 2008; 78: 175-82
- 32 Young IS, Tate S, Lightbody JH, McMaster D, Trimble ER. The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat. Free Radic Biol Med. 1995; 18: 833-40
- 33 Sena CM, Louro T, Matafome P, Nunes E, Monteiro P, Seiça R. Antioxidant and vascular effects of gliclazide in type 2diabetic rats fed high-fat diet. Physiol Res. 2009; 58: 203-9
- 34 Peterson SJ, Husney D, Kruger AL, Olszanecki R, Ricci F, Rodella LF et al. Long-term treatment with the apolipoprotein A1 mimetic peptide increases antioxidants and vascular repair in type I diabetic rats. J Pharmacol Exp Ther. 2007; 322: 514-20
- 35 Lu J, Zhu SM, Zang WJ, Xu XL, Luo HL, Yu XJ et al. Protective mechanism of adenosine to the rat arterial endothelial dysfunction induced by hydrogen peroxide. Biol Pharm Bull. 2007; 30: 1206-11
- 36 Roghani M, Baluchnejadmojarad T. Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats: underlying mechanisms. Vascul Pharmacol. 2009; 51: 84-9
- 37 Woodman OL, Malakul W. 3′,4′-Dihydroxyflavonol prevents diabetes-induced endothelial dysfunction in rat aorta. Life Sci. 2009; 85: 54-9
- 38 Pashkow FJ, Watumull DG, Campbell CL. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol. 2008; 101: 58D-68D
- 39 Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H. Astaxanthin, a carotenoid with potential in human health and nutrition. J Nat Prod. 2006; 69: 443-9
- 40 Naguib YM. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000; 48: 1150-4
- 41 Renier G. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a relevant target for diabetic vasculopathy?. Cardiovasc Hematol Disord Drug Targets. 2008; 8: 203-11
- 42 Li D, Mehta JL. Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation. 2000; 101: 2889-95
- 43 Mehta JL, Li D. Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor. J AmColl Cardiol. 2002; 39: 1429-35
- 44 Zou MH, Shi C, Cohen RA. Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite. J Clin Invest. 2002; 109: 817-26
- 45 Wang L, Zhang L, Yu Y, Wang Y, Niu N. The protective effects of taurine against early renal injury in STZ-induced diabetic rats, correlated with inhibition of renal LOX-1-mediated ICAM-1 expression. Ren Fail. 2008; 30: 763-71
- 46 Vincent AM, Hayes JM, McLean LL, Vivekanandan-Giri A, Pennathur S, Feldman EL. Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1. Diabetes. 2009; 58: 2376-85
- 47 Kazuyama E, Saito M, Kinoshita Y, Satoh I, Dimitriadis F, Satoh K. Endothelial dysfunction in the early- and late-stage type-2 diabetic Goto-Kakizaki rat aorta. Mol Cell Bio-chem. 2009; 332: 95-102
- 48 Sena CM, Nunes E, Louro T, Proenca T, Fernandes R, Boarder MR et al. Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Br J Pharmacol. 2008; 153: 894-906