Protective Role of Thymoquinone in Hyperlipidemia-Induced Liver Injury in LDL-R-/- Mice
Background: Hyperlipidemia, a heterogeneous group of disorders characterized by elevated levels of plasma lipids, causes serious health problems and can lead to fatty liver and nonalcoholic fatty liver disease. Thymoquinone (TQ), a major active component of Nigella sativa, can exert a vast array of biological effects. Various studies have reported that TQ protects against liver injury, and we previously reported that TQ reduces cardiac damage in mice fed a high-cholesterol diet (HD). However,
... et (HD). However, few studies have evaluated the effects of TQ on hyperlipidemia-induced liver injury. The aim of this study was to investigate the possible protective effects of TQ against liver injury in hyperlipidemia-induced LDL-R-/- mice.Methods: Eight-week-old male LDL-R-/- mice were randomly divided into three groups based on diet: normal diet (ND group, which was the control), high cholesterol diet (HD group), and HD mixed with TQ (HD + TQ group). All mice were fed for 8 weeks. Blood samples were obtained from the inferior vena cava, collected in serum tubes, and stored at −80 °C to investigate the serum lipoprotein profile. Longitudinal sections of liver tissues were fixed in 10% formalin and embedded in paraffin for histological evaluation. The remainder of the liver tissues was snap-frozen in liquid nitrogen for mRNA and immunoblotting analyses.Results: TQ administration significantly reduced liver histological alterations caused by hyperlipidemia. TQ mitigated hyperlipidemia-induced liver injury, as indicated by the suppression of increases in metabolic parameters (total cholesterol, triglyceride, and low-density lipoprotein-cholesterol), hepatic biochemical parameters (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), pyroptosis indicators (nucleotide-binding oligomerization domain-like receptor 3, interleukin [IL]-1β, and IL-18), a macrophage marker (CD68-positive cells), and phosphatidylinositide 3-kinase levels induced by the HD.Conclusions: These results indicate that TQ is a potential therapeutic agent for liver injury caused by hyperlipidemia.