Tauroursodeoxycholic Acid Alleviates HO-Induced Oxidative Stress and Apoptosis via Suppressing Endoplasmic Reticulum Stress in Neonatal Rat Cardiomyocytes

• Main Authors: Lin Zhang, Yanmin Wang
• Format: Article
• Language: English
• Published: SAGE Publishing 2018-07-01
• Series: Dose-Response
• Online Access: https://doi.org/10.1177/1559325818782631

Introduction: We aimed to test the mechanism of protective effects of tauroursodeoxycholic acid (TUDCA) on cardiovascular disease using cultured cardiomyocytes. Methods: Neonatal rat cardiomyocytes (NRCMs) were isolated and cultured and then the cells were divided into 4 groups based on the treatments: control group (cells treated with culture medium), H 2 O 2 /thapsigargin (TG) group (cells treated with oxidative stress and endoplasmic reticulum [ER] stress inducer), TUDCA group, and H 2 O 2 /TG + TUDCA group. The treated NRCMs were then subjected to serial analyses including flow cytometry, enzyme-linked immunosorbent assay, and Western blotting. Results: Tauroursodeoxycholic acid significantly attenuated H 2 O 2 -induced reactive oxygen species generation and lactate dehydrogenase release and restored H 2 O 2 -induced reductions of glutathione and superoxide dismutase levels in NRCMs. Tauroursodeoxycholic acid also alleviated H 2 O 2 -induced cardiomyocytes apoptosis, as well as the Bax/Bcl2 ratio compared with that of H 2 O 2 treated alone. In addition, TUDCA suppressed TG-induced ER stress as reflected by inversing cell viability and the expression levels of glucose-regulated protein 78 kDa and C/enhancer-binding protein homologous protein. Conclusion: Our data indicated that TUDCA-mediated inhibition on H 2 O 2 -induced oxidative stress and cardiomyocytes apoptosis was through suppressing ER stress, and TUDCA possesses the potential to be developed as therapeutic tool in clinical use for cardiovascular diseases.