Thymoquinone reduces cardiac damage caused by hypercholesterolemia in apolipoprotein E-deficient mice

Abstract

Background: Hypercholesterolemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that thymoquinone protected rats from doxorubicin-induced cardiotoxicity and cardiac damage. The aim of this study was to investigate the possible protective effects of thymoquinone against cardiac damage in apolipoprotein E knockout (ApoE-/-) mice. Methods: Eight-week-old male ApoE-/- mice were randomly divided into three groups: control group fed a normal diet (ND group), a high cholesterol diet (HD group) or HD mixed with thymoquinone (HD + TQ group). All groups were fed the different diets for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. Results: The metabolic characteristics of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP) were lower in ApoE-/-HD + TQ mice than in ApoE-/- HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) gene and protein expression was lower in the heart tissue of ApoE-/-HD + TQ mice than in those of ApoE-/-HD mice. Furthermore, the levels of macrophages and pro-inflammatory cytokines were lower in the cardiac tissues of ApoE-/-HD + TQ mice than in those of ApoE-/-HD mice. Conclusions: These results indicate that thymoquinone may provide a potential therapeutic target for cardiac damage caused by hypercholesterolemia.