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The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects

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Abstract

Hypercholesterolemia and oxidative stress have been implicated in the pathophysiology of atherosclerosis and coronary artery disease. We investigated whether the carotenoid bixin (BIX) may reduce oxidative damage, inflammatory response, and the atherosclerotic lesion induced by hypercholesterolemia in rabbits. Rabbits received regular chow (control) or a hypercholesterolemic diet (0.5 % cholesterol) alone or supplemented with BIX (10, 30 or 100 mg/kg body weight, b.w.) or simvastatin (15 mg/kg b.w.) for 60 days. Treatment with BIX or simvastatin reduced the atherosclerotic lesions in cholesterol-fed rabbits (up to 55 and 96 % reduction, respectively). This protective effect of BIX was accompanied by decrease in the levels of tumor necrosis factor alpha by 15 %, interleukin 6 by 19 %, lipid peroxidation by 60 %, non-high-density lipoprotein cholesterol (non-HDL-C) by 37 %, and triglycerides by 41 %. BIX increased by 160 % the HDL-C levels and decreased by 67 % the atherogenic index of hypercholesterolemic rabbits. In atherosclerotic rabbits, the non-protein thiol groups content and the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase were increased in the aortic tissue, whereas paraoxonase activity was reduced in the serum. All these changes were completely prevented by BIX or simvastatin treatment. These results demonstrate that BIX reduces the extent of atherosclerotic lesions and this effect was associated with the decrease in oxidative stress, inflammatory response, and improvement of dyslipidemia, which were most effectively controlled after treatment with 10–30 mg BIX/kg b.w. BIX consumption may, therefore, be an adjuvant to prevent atherosclerosis reducing risk factors for coronary diseases.

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Acknowledgments

This work was supported by fellowships from National Council for Scientific and Technological Development (CNPq) and Co-ordination for the Improvement of Higher Education Staff (CAPES) and had financial support from CNPq (475597/2010-9 and 552440/2011-6) and Edital Capes 11/2009 and 27/2010 - Pró-Equipamentos Institucional. The authors thank Christian Hansen Co., Ltd., Denmark, for the kind donation of the BIX product and Doles, Brazil, for the kind donation of biochemical kits.

Conflict of interest

All authors declare that there are no funding sources, employment, or personal financial competing interests that could influence the position presented in this manuscript. In addition, authors are not aware of any institutional competing interest of any nature or kind.

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Authors and Affiliations

  1. Graduate Program on Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, 97105-9003, Brazil

    Sabrina Somacal, Andréia Quatrin & Miguel Roehrs

  2. Integrated Center for Laboratory Analysis Development (NIDAL), Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Cassieli G. Figueiredo, Amanda R. Ruviaro, Lisiane Conte & Tatiana Emanuelli

  3. Department of Food Science, Federal University of Rio Grande do Sul, Porto Alegre, RS, 91501-970, Brazil

    Paula R. Augusti

  4. Polytechnical High School, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Ione T. Denardin

  5. Department of Morphology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Jocieli Kasten & Marcelo L. da Veiga

  6. Department of Health Sciences, Lutheran University of Brazil, Santa Maria, RS, 97020-001, Brazil

    Marta M. F. Duarte

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  1. Sabrina Somacal
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Somacal, S., Figueiredo, C.G., Quatrin, A. et al. The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects. Mol Cell Biochem 403, 243–253 (2015). https://doi.org/10.1007/s11010-015-2354-x

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