Abo-Zaid Omayma Ar, Moawed Fatma Sm, Ismail Effat Soliman, Ahmed Esraa S A
Biochemistry and Molecular Biology Department, Faculty of Vet. Med. Benha University, Egypt.
Health Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Food Chem Toxicol. 2023 Feb;172:113602. doi: 10.1016/j.fct.2023.113602. Epub 2023 Jan 4.
The endoplasmic reticulum (ER) controls many biological functions besides maintaining the function of liver cells. Various studies reported the role of the ER stress and UPR signaling pathway in various liver diseases via triggering hepatocytes apoptosis. This study aims to investigate the suppressive effect of β-sitosterol (βS) on apoptosis associated with liver injury and ER stress.
Liver damage in rats was induced by TAA (150 mg/kg I.P twice a week/3 weeks) and γ-irradiation (single dose 3.5 Gy) and treated with βS (20 mg/kg daily for 30 days). Serum aminotransferase activity, lipid profile and lipid metabolic factors were measured beside liver oxidative stress and inflammatory markers. Moreover, the hepatic expression of ER stress markers (inositol-requiring enzyme 1 alpha (IRE1α), X-box-binding protein 1 (XBP1) and CCAAT/enhancer binding protein homologous protein (CHOP) and apoptotic markers were detected together with histopathological examination.
βS diminished the aminotransferase activity, the oxidative stress markers as well as the inflammatory mediators. Furthermore, βS lowered the circulating TG and TC and the hepatic lipotoxicity via the suppression of lipogenesis (Srebp-1c) and improved the β-oxidation (Pparα and Cpt1a) together with the mitochondrial biogenesis (Pgc-1 α). Moreover, the upregulated levels of ER stress markers were reduced upon treatment with βS, which consequently attenuated hepatic apoptosis.
βS relieves hepatic injury, ameliorates mitochondrial biogenesis, and reduces lipotoxicity and apoptosis via inhibition of CHOP and ER stress response.
内质网（ER）除维持肝细胞功能外，还控制许多生物学功能。各种研究报道了内质网应激和未折叠蛋白反应（UPR）信号通路通过触发肝细胞凋亡在各种肝脏疾病中的作用。本研究旨在探讨β-谷甾醇（βS）对与肝损伤和内质网应激相关的细胞凋亡的抑制作用。
用硫代乙酰胺（TAA，150mg/kg腹腔注射，每周两次，共3周）和γ射线照射（单次剂量3.5Gy）诱导大鼠肝损伤，并用βS（20mg/kg每日，共30天）进行治疗。除了检测肝脏氧化应激和炎症标志物外，还测定了血清转氨酶活性、血脂谱和脂质代谢因子。此外，检测内质网应激标志物（肌醇需要酶1α（IRE1α）、X盒结合蛋白1（XBP1）和CCAAT/增强子结合蛋白同源蛋白（CHOP））的肝脏表达以及凋亡标志物，并进行组织病理学检查。
βS降低了转氨酶活性、氧化应激标志物以及炎症介质。此外，βS通过抑制脂肪生成（Srebp-1c）降低了循环中的甘油三酯（TG）和总胆固醇（TC）以及肝脏脂毒性，并改善了β氧化（Pparα和Cpt1a）以及线粒体生物发生（Pgc-1α）。此外，用βS治疗后，内质网应激标志物上调的水平降低，从而减轻了肝脏细胞凋亡。
βS通过抑制CHOP和内质网应激反应减轻肝损伤，改善线粒体生物发生，并降低脂毒性和细胞凋亡。
