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Combined effect of astaxanthin and squalene on oxidative stress in vivo

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Abstract

Obesity and diabetes, risk factors for metabolic syndrome, are characterized by oxidative stress and inflammatory responses. Marine biofunctionals, astaxanthin (Ax) and squalene (SQ), were evaluated for their combined effect. Groups of male KK-A y mice were fed high fat/sucrose diet for 4 weeks, supplemented with either 0.1 %Ax, 2 %SQ or 0.1 %Ax + 2 %SQ. In comparison to control, Sod was elevated in only Ax + SQ. However, Gpx was highest in Ax + SQ, indicating the combined antioxidant effect of Ax and SQ. This was supported by elevated mRNA expression of Sod1 and Gpx1. Except adiponectin (elevated in Ax and Ax + SQ), expression of other inflammatory markers was not altered. Blood glucose levels were decreased in SQ and Ax + SQ while liver triglycerides decreased in SQ group. This is the first in vivo study demonstrating combined effects of Ax and SQ resulting in antioxidant effects and modulation of glucose/triglyceride levels. This study highlights the benefit of utilizing Ax and SQ together for management of obesity/diabetes.

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Abbreviations

Ax:

Astaxanthin

BAT:

Brown adipose tissue

Cat:

Catalase

Cox:

Cyclooxygenase

DHA:

Docosahexaenoic acid

DPPP:

Diphenyl-1-pyrenylphosphine

EPA:

Eicosapentaenoic acid

ERK:

Extracellular-signal regulated kinase

Gpx:

Glutathione peroxidase

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

HDL-C:

High density cholesterol

iNOS:

Inducible nitric oxide synthase

MAPK:

Mitogen-activated protein kinase

MCP:

Monocyte chemoattractant protein

NF:

Nuclear factor

PPAR:

Peroxisome proliferator-activated receptor

Sod:

Superoxide dismutase

SQ:

Squalene

TG:

Triglycerides

TNF:

Tumor necrosis factor

WAT:

White adipose tissue

References

  1. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R (2005) Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 111:1448–1454

    Article  PubMed  Google Scholar 

  2. Rains JL, Jain SK (2011) Oxidative stress, insulin signalling, and diabetes. Free Radic Biol Med 50:567–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yuan J-P, Peng J, Yin K, Wang J-H (2011) Potential health-promoting effects of astaxanthin: a high-value carotenoid mostly from microalgae. Mol Nutr Food Res 55:150–165

    Article  CAS  PubMed  Google Scholar 

  4. Otsuka T, Shimazawa M, Nakanishi T, Ohno Y, Inoue Y, Tsuruma K, Ishibashi T, Hara H (2013) The protective effects of a dietary carotenoid, astaxanthin, against light-induced retinal damage. J Pharmacol Sci 123:209–218

    Article  CAS  PubMed  Google Scholar 

  5. Hashimoto H, Arai K, Hayashi S, Okamoto H, Takahashi J, Chikuda M, Obara Y (2013) Effects of astaxanthin on antioxidation in human aqueous humour. J Clin Biochem Nutr 53:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Choi HD, Kim JH, Chang MJ, Kyu-Youn Y, Shin WG (2011) Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res 25:1813–1818

    Article  CAS  PubMed  Google Scholar 

  7. Tripathi DN, Jena GB (2009) Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact 180:398–406

    Article  CAS  PubMed  Google Scholar 

  8. Augusti PR, Conterato GMM, Somacal S, Sobieski R, Spohr PR, Torres JV, Charao MF, Moro AM, Rocha MP, Garcia SC, Emanuelli T (2008) Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats. Food Chem Toxicol 46:212–219

    Article  CAS  PubMed  Google Scholar 

  9. Nakajima Y, Inokuchi Y, Shimazawa M, Otsubo K, Ishibashi T, Hara H (2008) Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in vitro and in mice in-vivo. J Pharm Pharmacol 60:1365–1374

    Article  CAS  PubMed  Google Scholar 

  10. Das B, Antoon R, Tsuchida R, Lotfi S, Morozova O, Farhat W, Malkin D, Koren G, Yeger H, Baruchel S (2008) Squalene selectively protects mouse bone marrow progenitors against cisplatin and carboplatin–induced cytotoxicity in vivo without protecting tumor growth. Neoplasia 10:1105–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cardeno A, Aparicio-Soto M, Montserrat-de la Paz S, Bermudez B, Muriana FJG, Alarcon-de-la-Lastra C (2015) Squalene targets pro and anti-inflammatory mediators and pathways to modulate over activation of neutrophils, monocytes and macrophages. J Funct Foods 14:779–790

    Article  CAS  Google Scholar 

  12. Farvin KHS, Anandan R, Kumar SHS, Shiny KS, Mathew S, Sankar TV, Nair PGV (2006) Cardioprotective effect of squalene on lipid profile in isoprenaline-induced myocardial infarction in rats. J Med Food 9:531–536

    Article  CAS  PubMed  Google Scholar 

  13. Relas H, Gylling H, Miettinen TA (2000) Dietary squalene increases cholesterol synthesis measured with serum noncholesterol sterols after a single oral dose in humans. Atherosclerosis 152:377–383

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Z, Yeung WK, Huang Y, Chen Z-Y (2002) Effect of squalene and shark liver oil on serum cholesterol level in hamsters. Int J Food Sci Nutr 53:411–418

    Article  CAS  PubMed  Google Scholar 

  15. Saw CLL, Yang AY, Guo Y, Kong A-NT (2013) Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2–ARE pathway. Food Chem Toxicol 62:869–875

    Article  CAS  PubMed  Google Scholar 

  16. Dhandapani N, Ganesan B, Anandan R, Jeyakumar R, Rajaprabhu D, Ezhilan RA (2007) Synergistic effects of squalene and polyunsaturated fatty acid concentrate on lipid peroxidation and antioxidant status in isoprenaline-induced myocardial infarction in rats. Afr J Biotechnol 6:1021–1027

    CAS  Google Scholar 

  17. Ravi Kumar S, Narayan B, KizawaY Hosokawa M, Miyashita K (2015) Does squalene alter the antioxidant potential of astaxanthin and fucoxanthinol? In vitro evidence in RAW264.7 cells, a murine macrophage. J Food Sci Tech. doi:10.1007/s13197-015-2077-8

    Google Scholar 

  18. Yasui Y, Hosokawa M, Mikami N, Miyashita K, Tanaka T (2011) Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chem Biol Interact 193:79–87

    Article  CAS  PubMed  Google Scholar 

  19. Macedo RC, Bolin AP, Marin DP, Otton R (2010) Astaxanthin addition improves human neutrophils function: in vitro study. Eur J Nutr 49:447–457

    Article  CAS  PubMed  Google Scholar 

  20. Manabe E, Handa O, Naito Y, Mizushima K, Akagiri S, Adach S, Takagi T, Kokura S, Maoka T, Yoshikawa T (2008) Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling. J Cell Biochem 103:1925–1937

    Article  CAS  PubMed  Google Scholar 

  21. Pashkow FJ, Watumull DG, Campbell CL (2008) Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol 101S:58D–68D

    Article  Google Scholar 

  22. Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951

    CAS  PubMed  Google Scholar 

  23. deCastro LIA, Soares RAM, Saldiva PHN, Ferrari RA, Miguel AMRO, Almeida CAS, Areˆas JAG (2013) Amaranth oil increased fecal excretion of bile acid but had no effect in reducing plasma cholesterol in hamsters. Lipids 48:609–618

    Article  Google Scholar 

  24. Farvin KHS, Anandan R, Kumar SHS, Shiny KS, Mathew S, Sankar TV, Nair PGV (2006) Cardioprotective effect of squalene on lipid profile in isoprenaline-induced myocardial infarction in rats. J Med Food 9:531–536

    Article  CAS  PubMed  Google Scholar 

  25. Smith D, Espino-Montoro A, Perez-Jimenez F, Pedro-Botet J, Pereperez JJ, Ordovas JM (2000) Effect of a high saturated fat and cholesterol diet supplemented with squalene or β-sitosterol on lipoprotein profile in F1B hamsters. Nutr Res 20:1309–1318

    Article  CAS  Google Scholar 

  26. Folch J, Lees M, Stanley GHS (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 26:497–509

    Google Scholar 

  27. Gabas-Rivera C, Barranquero C, Martınez-Beamonte R, Navarro MA, Surra JC, Osada J (2014) Dietary squalene increases high density lipoprotein-cholesterol and paraoxonase 1 and decreases oxidative stress in mice. PLoS One 9:e104224

    Article  PubMed  PubMed Central  Google Scholar 

  28. Liu Y, Xu X, Bi D, Wang X, Zhang X, Dai H, Chen S, Zhang W (2009) Influence of squalene feeding on plasma leptin, testosterone and blood pressure in rats. Indian J Med Res 129:150–153

    CAS  PubMed  Google Scholar 

  29. Buddhan S, Sivakumar R, Dhandapani N, Ganesan B, Anandan R (2007) Protective effect of dietary squalene supplementation on mitochondrial function in liver of aged rats. Prostaglandins Leukot Essen Fatty Acids 76:349–355

    Article  CAS  Google Scholar 

  30. Farvin KHS, Anandan R, Kumar SHS, Shiny KS, Sankar TV, Thankappan TK (2004) Effect of squalene on tissue defence system in isoproterenol-induced myocardial infarction in rats. Pharmacol Res 50:231–236

    Article  CAS  Google Scholar 

  31. Moreno JJ (2003) Effect of olive oil minor components on oxidative stress and arachidonic acid mobilization and metabolism by macrophages raw 264.7. Free Radic Biol Med 35:1073–1081

    Article  CAS  PubMed  Google Scholar 

  32. Baeza I, Fdez-TresguerresJ Ariznavarreta C, De la Fuente M (2010) Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats. Biogerontology 11:687–701

    Article  CAS  PubMed  Google Scholar 

  33. Jia Y, Wu C, Kim J, Kim B, Lee S-J (2015) Astaxanthin reduces hepatic lipid accumulations in high-fat fed C57BL/6 J mice via activation of peroxisome proliferator-activated receptor (PPAR) alpha and inhibition of PPAR gamma and Akt. J Nutr Biochem. doi:10.1016/j.jnutbio.2015.09.015

    PubMed Central  Google Scholar 

  34. Park JS, Chyun JH, Kim YK, Line LL, Chew BP (2010) Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab 7:18–24

    Article  Google Scholar 

  35. Aguilera Y, Dorado ME, Prada FA, Martínez JJ, Quesada A, Ruiz-Gutieŕrez V (2005) The protective role of squalene in alcohol damage in the chick embryo retina. Exp Eye Res 80:535–543

    Article  CAS  PubMed  Google Scholar 

  36. Tsuchiya M, Hosaka M, Moriguchi T, Zhang S, Suda M, Yokota-Hashimoto H, Shinozuka K, Takeuchi T (2010) Cholesterol biosynthesis pathway intermediates and inhibitors regulate glucose-stimulated insulin secretion and secretory granule formation in pancreatic β-cells. Endocrinology 151:4705–4716

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by “Scientific technique research promotion program for agriculture, forestry, fisheries and food industry” and partially supported by a National Project for the Formation of Tohoku Marine Science Center from MEXT (Ministry of Education, Culture, Sports, Science& Technology in Japan). SRK and BN are grateful to Japan Society for Promotion of Science (JSPS) for Post-Doctoral Fellowship and Invitation Fellowship, respectively.

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Correspondence to Sangeetha Ravi Kumar or Kazuo Miyashita.

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Ravi Kumar, S., Narayan, B., Sawada, Y. et al. Combined effect of astaxanthin and squalene on oxidative stress in vivo. Mol Cell Biochem 417, 57–65 (2016). https://doi.org/10.1007/s11010-016-2713-2

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