Obeticholic acid protects against lithocholic acid-induced exogenous cell apoptosis during cholestatic liver injury

• Published in: Life sciences (1973) 2024-01, Vol.337, p.122355-122355, Article 122355
• Main Authors: Lu, Qian, Zhu, Yangping, Wang, Changling, Zhang, Rongmi, Miao, Yingying, Chai, Yuanyuan, Jiang, Zhenzhou, Yu, Qinwei
• Format: Article
• Language: English
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.122355

Lithocholic acid (LCA)-induced cholestasis was accompanied by the occurrence of apoptosis, which indicated that anti-apoptosis was a therapeutic strategy for primary biliary cholangitis (PBC). As an agonist of (Farnesoid X receptor) FXR, we supposed that the hepatoprotection of Obeticholic acid (OCA) against cholestatic liver injury is related to anti-apoptosis beside of the bile acids (BAs) regulation. Herein, we explored the non-metabolic regulating mechanism of OCA for resisting LCA-induced cholestatic liver injury via anti-apoptosis. LCA-induced cholestatic liver injury mice were pretreated with OCA to evaluate its hepatoprotective effect and mechanism. Biochemical and pathological indicators were used to detect the protective effect of OCA on LCA-induced cholestatic liver injury. The bile acids (BAs) profile in serum was detected by LC-MS/MS. Hepatocyte BAs metabolism, apoptosis and inflammation related genes and proteins alteration were investigated by biochemical determination. OCA improved LCA-induced cholestasis and hepatic apoptosis in mice. The BA profile in serum was changed by OCA mainly manifested as a reduction of taurine-conjugated bile acids, which was due to the upregulation of FXR-related bile acid efflux transporters bile salt export pump (BSEP), multi-drug resistant associated protein 2 (MRP2), MRP3 and multi-drug resistance 3 (MDR3). Apoptosis related proteins cleaved caspase-3, cleaved caspase-8 and cleaved PARP were obviously reduced after OCA treatment. OCA improved LCA-induced cholestatic liver injury via FXR-induced exogenous cell apoptosis, which will provide new evidence for the application of OCA to ameliorate PBC in clinical.