Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 241; no. 4; pp. 426 - 436
• Main Authors: Shehatou, George SG, Suddek, Ghada M
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2016
• Subjects: Animals; Anticholesteremic Agents - administration & dosage; Antioxidants - administration & dosage; Aorta - pathology; Atherosclerosis - prevention & control; C-Reactive Protein - analysis; Diet, Atherogenic; Histocytochemistry; Hypercholesterolemia - complications; Immunohistochemistry; Isothiocyanates - administration & dosage; L-Lactate Dehydrogenase - blood; Lipids - blood; Male; NF-kappa B - analysis; Original Research; Rabbits; Serum - chemistry; Tunica Intima - pathology; Tunica Media - pathology; NF-κB; sulforaphane; nitric oxide; Hypercholesterolemia; lipid profile; endothelial dysfunction; oxidative stress
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/1535370215609695

The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation.