Thioridazine Induces Cardiotoxicity via Reactive Oxygen Species-Mediated hERG Channel Deficiency and L-Type Calcium Channel Activation

Figure 4

ROS generation mediates the ER stress pathway induced by THIO. (a) Macrographs of DCFDA fluorescence were detected with the confocal microscope. THIO induced a significant increase in the production of ROS, which was significantly decreased in hERG-HEK293 cells pretreated with NAC for 1 h. Original magnification, ×200. (b) Values for ROS production were quantified using ImageJ (NIH, Bethesda, MD). Values are from three independent experiments and normalized to respective controls. (c, d) hERG-HEK293 cells were treated as in (a) and the mean fluorescence intensity quantified by flow cytometry. (e–f) ATF6, cleaved ATF6, and hERG expression in hERG-HEK293 cells treated with THIO (3 μM) in the presence or absence of NAC (3 mM) were detected by Western blot. . vs. control and vs. THIO.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)