Thymoquinone reduces kidney damage in apolipoprotein E-deficient mice fed a high-cholesterol diet

Hypercholesterolemia is a well-established risk factor for kidney injury that can lead to chronic kidney disease (CKD). Thymoquinone (TQ) is one of the most active ingredients in Nigella Sativa seeds. It has a variety of beneficial properties including anti-oxidative and anti-inflammatory activities. TQ exerts positive effects on DOX-induced nephropathy and ischaemia-reperfusion induced kidney injury in rats. The goal of this study was to investigate the possible protective effects of thymoquinone against kidney injury in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old male ApoE(-/)- mice were randomly divided into the following 3 groups: a control group fed a normal diet (ND group), a group fed a high-cholesterol diet (HD group) and a group fed HD mixed with thymoquinone (HD + TQ group). All groups were given the diet for 8 weeks. Metabolic characteristics including total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-c) were lower in ApoE(-/-) HD + TQ mice than in ApoE(-/-) HD mice. Oil-red O staining revealed excessive lipid deposition in the kidneys of ApoE(-/-) HD mice; however, it was significantly suppressed in the ApoE(-/-) HD + TQ mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) gene and protein expression was lower in the kidney tissues of ApoE(-/-) HD + TQ mice than those of ApoE(-/-) HD mice. Furthermore, macrophages and pro-inflammatory cytokines were lower in the kidney tissues of ApoE(-/-) HD + TQ mice than in the ApoE(-/-) HD mice. These results indicate that thymoquinone may be a potential therapeutic agent for kidney damage from hypercholesterolemia.