Abstract Cholesterol is a lipid molecule of great biological importance to animal cells. Dysregulation of cholesterol metabolism leads to raised blood total cholesterol levels, a clinical condition called hypercholesterolemia. Evidence has shown that hypercholesterolemia is associated with the development of liver and heart disease. One of the mechanisms underlying heart and liver alterations induced by hypercholesterolemia is oxidative stress. In this regard, in several experimental studies, gold nanoparticles (AuNP) displayed antioxidant properties. We hypothesized that hypercholesterolemia causes redox system imbalance in the liver and cardiac tissues, and AuNP treatment could ameliorate it. Young adult male Swiss mice fed a regular rodent diet or a high cholesterol diet for eight weeks and concomitantly treated with AuNP (2.5 μg/kg) or vehicle by oral gavage. Hypercholesterolemia increased the nitrite concentration and glutathione (GSH) levels and decreased the liver’s superoxide dismutase (SOD) activity. Also, hypercholesterolemia significantly enhanced the reactive oxygen species (ROS) and GSH levels in cardiac tissue. Notably, AuNP promoted the redox system homeostasis, increasing the SOD activity in hepatic tissue and reducing ROS levels in cardiac tissue. Overall, our data showed that hypercholesterolemia triggered oxidative stress in mice’s liver and heart, which was partially prevented by AuNP treatment.

RESUMO A oxidação da lipoproteína de baixa densidade (LDL) apresenta um papel importante na patogênese da aterosclerose. Nesse sentido, reduzir a oxidação da LDL é uma abordagem importante para diminuir o risco de aterosclerose. Compostos orgânicos de selênio têm demonstrado propriedades ateroprotetoras promissoras em modelos experimentais. Neste estudo, nós testamos a capacidade ateroprotetora in vitro de um composto orgânico de selênio modificado, Composto HBD, em proteger a LDL isolada da oxidação, bem como a formação de células espumosas. Além disso, a atividade mimética da enzima glutationa peroxidase (GPx) do composto HBD foi analisada com o intuito de explorar os mecanismos relacionados com os efeitos protetores apresentados pelo Composto HBD. O Composto HBD reduziu a formação de dienos conjugados induzida pelo Cu2+ em uma maneira dependente da concentração. A parte proteica da LDL também foi protegida da oxidação induzida pelo Cu2+. Além disso, o composto HBD eficientemente diminuiu a formação de células espumosas em macrófagos J774 expostos à LDL oxidada. Nós observamos que os efeitos ateroprotetores deste composto podem ser, ao menos em parte, relacionados à sua atividade mimética da GPx. Nossos resultados demonstraram um efeito in vitro promissor do Composto HBD em reduzir a toxicidade induzida pela LDL. Nesse sentido, um outro estudo in vivo para investigar de maneira mais detalhada os efeitos antioxidantes e ateroprotetores deste composto pode ser considerado.

ABSTRACT Oxidation of low-density lipoprotein (LDL) has been strongly suggested to play a significant role in the pathogenesis of atherosclerosis. Thus, reducing LDL oxidation is a potential approach to decrease the risk of the atherosclerosis. Organoselenium compounds have demonstrated promising atheroprotective properties in experimental models. Herein, we tested the in vitro atheroprotective capability of a modified organoselenium compound, Compound HBD, in protecting isolated LDL from oxidation as well as foam cells formation. Moreover, the glutathione peroxidase (GPx)-like activity of Compound HBD was analyzed in order to explore the mechanisms related to the above-mentioned protective effects. The Compound HBD in a concentration-dependent manner reduced the Cu2+-induced formation of conjugated dienes. The protein portion from LDL were also protected from Cu2+-induced oxidation. Furthermore, the Compound HBD efficiently decreased the foam cell formation in J774 macrophage cells exposed to oxidized LDL. We found that the atheroprotective effects of this compound can be, at least in part, related to its GPx-like activity. Our findings demonstrated an impressive effect of Compound HBD against LDL-induced toxicity, a further in vivo study to investigate in more detail the antioxidant and antiatherogenic effects of this compound could be considered.