Investigation of the effects of chronic L-arginine supplementation on paraoxonase-1 activity in high-cholesterol diet-induced hypercholesterolemia model in rats

Abstract Background Hypercholesterolemia is a cardinal driver of atherosclerotic cardiovascular disease (ASCVD), one of the major global mortality causes. Associated oxidative stress and lipid peroxidation perturbes HDL-associated paraoxonase-1 (PON1) activity. This study investigates the effects of chronic L-arginine supplementation—a nitric oxide precursor—on PON1 activity, lipid profiles, and oxidative stress in hypercholesterolemic rats. Methods Subjects were randomly selected and divided into four equal groups (n=36): control (C), L-arginine (LA), hypercholesterolemia (HC), and hypercholesterolemia + L-arginine (HC+LA). After 8-weeks study period, serum lipid levels, PON1, and malondialdehyde (MDA) levels were measured, and the atherogenic index (ATI) was calculated. Atherosclerotic lesions were evaluated histopathologically. Results PON1, MDA, and lipid levels, as well as ATI and the PON1/HDL ratio, were increased in the HC group. These variables were significantly lower in the HC+LA group than in the HC group. Moreover, a significant increase in TG, VLDL, and PON1 levels was observed in the LA group compared with the C group. A strong negative correlation was found between PON1 and MDA levels. Conclusions Chronic L-arginine supplementation was effective in reducing ATI, LDL, and oxidative stress, and in alleviating structural vascular changes in high cholesterol diet-induced hypercholesterolemia model rats.