β-Sitosterol mitigates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced hepatic injury in γ-irradiated rats

• Published in: Food and chemical toxicology 2023-02, Vol.172, p.113602-113602, Article 113602
• Main Authors: Abo-Zaid, Omayma AR, Moawed, Fatma SM, Ismail, Effat Soliman, Ahmed, Esraa S.A.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - metabolism; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Endoribonucleases - metabolism; Hepatocytes - drug effects; Liver - pathology; Liver disease; Protein Serine-Threonine Kinases - metabolism; Radiation apoptosis; Rats; Sitosterols - pharmacology; Thioacetamide; Thioacetamide - metabolism; Thioacetamide - pharmacology; Transaminases - metabolism; β-Sitosterol
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.113602

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. Methods: 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. Results: 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. Conclusion: βS relieves hepatic injury, ameliorates mitochondrial biogenesis, and reduces lipotoxicity and apoptosis via inhibition of CHOP and ER stress response. •β-Sitosterol (βS) is a valuable natural product with various biological effects.•Thioacetamide/γ-irradiation impairs oxidative status and induces liver toxicity.•βS relieves liver injury and ameliorates mitochondrial functions and lipotoxicity.•β-sitosterol inhibits apoptosis via inhibition of CHOP and ER stress response.