Sulforaphane Attenuates Homocysteine-Induced Endoplasmic Reticulum Stress through Nrf-2-Driven Enzymes in Immortalized Human Hepatocytes

In the present study, we investigated the potential efficacy of cruciferous vegetable-derived sulforaphane (SFN) in improving homocysteine (HCY)-stressed cells. After human hepatocyte line HHL-5 was preincubated with SFN and subsequently with 10 mmol/L HCY, SFN improved the pathologic changes which are caused by HCY, including cell morphological abnormality, endoplasmic reticulum (ER) swelling, excessive generation of reactive oxygen species (ROS), the increased malondialdehyde (MDA) levels, as well as the increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Phase II enzymes, thioredoxin reductase-1 (TrxR-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), were involved in the protective effect of SFN against injury by HCY. The ER stress-specific proteins, such as glucose-regulated protein-78 (GRP78) and protein kinase RNA (PKR)-like ER kinase (PERK), were strikingly abolished by SFN. Furthermore, Nrf-2 translocation was enhanced by SFN, which lead to the induction of TrxR-land NQO1.