l-Arginine and vitamin C attenuate pro-atherogenic effects of high-fat diet on biomarkers of endothelial dysfunction in rats

High-fat diet (HFD) is known to cause endothelial dysfunction and contribute to atherosclerosis progression. The objective of this study was to evaluate the efficacy of l-arginine (l-Arg) and vitamin C supplementation as a potentially useful strategy for modulation of serum homocysteine (Hcy) levels, tumor necrosis factor alpha (TNF-α), oxidative stress, and insulin resistance induced by HFD in rats. Six weeks-old female and male Wistar rats were divided into five groups of twelve rats each and treated for six weeks with: group 1, standard diet; group 2, HFD; group 3, HFD supplemented with l-Arg (20 g/kg diet); group 4, HFD supplemented with l-Arg (20 g/kg diet) plus vitamin C (100 mg/kg diet); group 5, HFD supplemented with vitamin C (100 mg/kg diet). HFD significantly elevated TNF-α, reduced total antioxidant status (TAS), and increased insulin resistance (HOMA-IR). Significant increases of total cholesterol (TCH), LDL cholesterol (LDL), triglyceride (TG) and a decrease of HDL cholesterol (HDL) were observed in HFD rats. Supplementation with l-Arg prevented the decrease of TAS and the increases in HOMA-IR, LDL, and TG levels. Moreover, Hcy and TNF-α levels were reduced in l-Arg supplemented group. Supplementation with vitamin C significantly atenuated TAS decrease and lowered LDL levels. l-Arg plus vitamin C enhanced l-Arg effect on TAS and protected against TNF-α increase. Western blot analysis showed that l-Arg supplementation of HFD rats reduced the level of protein carbonyls. Taken together, these findings indicate that supplemental l-arginine and/or vitamin C, by their abilities to modulate biomarkers of HFD-induced endothelial dysfunction, are anti-atherogenic.