title: The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects.
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.
authors.affiliation: Graduate Program on Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, 97105-9003, Brazil.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Somacal
authors.forename: Cassieli G
authors.initials: CG
authors.lastname: Figueiredo
authors.forename: Andréia
authors.initials: A
authors.lastname: Quatrin
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Ruviaro
authors.forename: Lisiane
authors.initials: L
authors.lastname: Conte
authors.forename: Paula R
authors.initials: PR
authors.lastname: Augusti
authors.forename: Miguel
authors.initials: M
authors.lastname: Roehrs
authors.forename: Ione T
authors.initials: IT
authors.lastname: Denardin
authors.forename: Jocieli
authors.initials: J
authors.lastname: Kasten
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: da Veiga
authors.forename: Marta M F
authors.initials: MM
authors.lastname: Duarte
authors.forename: Tatiana
authors.initials: T
authors.lastname: Emanuelli
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000473:pathology; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008055:Lipids; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D002338:Carotenoids; C004588:bixin; D019821:Simvastatin