Sulforaphane in the protection of cardiomyocytes from oxidative stress.

none6The recognition that oxidative stress plays a major role in the pathophysiology of cardiac disorders has led to extensive investigation of the protective effects of exogenous antioxidants. Another strategy may be through induction of the endogenous antioxidants/phase 2 enzymes. Accordingly, this study was undertaken to investigate the inducibility of endogenous antioxidants/phase 2 enzymes (reduced glutathione (GSH), GSH peroxidase (GPx), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1)) by the isothiocyanate sulforaphane (SF) in cultured rat cardiomyocytes. Due to the role of the nuclear factors E2-related factor 1 (nrf1) and 2 (nrf2) in inducing phase 2 enzymes, we also investigated the role of SF in the translocation of these factors from cytosol to the nucleus. Enzymatic activities were determined spectrophotometrically, GSH by the fluorescent indicator monochlorobimane, reactive oxygen species (ROS) formation spectrofluorimetrically by 2′,7′-dichlorofluorescein diacetate, cell viability by MTT assay, nrf1 and nrf2 translocation to nucleus by laser confocal microscopy. GPx activity was not affected by SF, but GR, GST and NQO1 activities and GSH levels increased with a time-dependent pattern following SF supplementation. As a consequence SF supplementation led to decreased ROS levels and increased cell viability following oxidative stress. Laser confocal microscopy revealed the translocation of both nrf1 and nrf2 to the nucleus. In conclusion, SF acts as an indirect antioxidant leading to cardioprotection against oxidative stress.noneM. Malaguti; C. Angeloni; E. Leoncini; E. Pagnotta; P. Biagi; S. HreliaM. Malaguti; C. Angeloni; E. Leoncini; E. Pagnotta; P. Biagi; S. Hreli