Tauroursodeoxycholic Acid Alleviates H(2)O(2)-Induced Oxidative Stress and Apoptosis via Suppressing Endoplasmic Reticulum Stress in Neonatal Rat Cardiomyocytes

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.