S‐allyl‐L‐cysteine protects hepatocytes from indomethacin‐induced apoptosis by attenuating endoplasmic reticulum stress

FEBS Open Bio

Rui Cui¹  Peng Chen¹  Mingdao Hu¹  Feng Liu¹  Henghai Yu¹  Yuling Ren²  Chen Chen² 

[1] Department of Hepatopancreatobiliary Surgery The Second Affiliated Hospital of Kunming Medical University Kunming China;Department of Ophthalmology The Second People's Hospital of Yunnan Province Kunming China;

关键词: apoptosis;    endoplasmic reticulum stress;    hepatocyte;    indomethacin;    S‐allyl‐l‐cysteine;   

DOI  :  10.1002/2211-5463.12945

来源: DOAJ

【 摘 要 】

Drug‐induced liver injury (DILI) can lead to acute liver failure, a lethal condition which may require liver transplantation. Hepatotoxicity associated with nonsteroidal anti‐inflammatory drugs (NSAIDs) accounts for ~ 10% of all DILI. In the current study, we determined whether indomethacin, one of the most commonly used NSAIDS, induced apoptosis in hepatocytes and investigated the underlying mechanism. Meanwhile, we investigated the protective effect of S‐allyl‐L‐cysteine (SAC), an active garlic derivative, on indomethacin‐induced hepatocyte apoptosis, and its implication on endoplasmic reticulum (ER) stress. We found that indomethacin triggered ER stress, as indicated by the elevated expression of phosphorylated eukaryotic translation initiation factor 2α (eIF2α), C/EBP homologous protein (CHOP) and spliced XBP1 in a rat liver BRL‐3A cell line. Following indomethacin treatment, caspase 3 activation and hepatocyte apoptosis were also observed. Inhibition of ER stress by chemical chaperone 4‐phenyl butyric acid alleviated cell apoptosis caused by indomethacin, indicating that ER stress is involved in indomethacin‐induced hepatocyte apoptosis. Moreover, SAC abated indomethacin‐induced eIF2α phosphorylation, inhibited CHOP upregulation and its nuclear translocation, abrogated the activation of caspase 3 and finally, protected hepatocytes from apoptosis. In conclusion, SAC protects indomethacin‐induced hepatocyte apoptosis through mitigating ER stress and may be suitable for development into a potential new therapeutic agent for the treatment of DILI.

【 授权许可】

Unknown