We used HPLC to test the concentration of endogenous DMSO in PC12 cells (see details in supplementary methods). The endogenous cellular DMSO was at 5.73 nmol per 5 × 106 cell count. As shown in Fig. 6A, the DMSO content in H2O2‐treated groups raised significantly to 184 ± 16% and 281 ± 20% of control, respectively (**P < 0.01 vs. control, Fig. 6A). Then, MsrA shRNA was used to test whether MsrA played a vital role in the formation of DMSO (Fig. 6B). Knockdown of MsrA exhibited little effect on the concentration of endogenous DMSO in PC12 cells (Fig. 6B), which may be resulted from a bidirectional role of MsrA in the endogenous DMSO content: increasing DMSO generation under oxidative stress and reducing DMSO back to DMS using reducing substrates. Under H2O2‐induced oxidative stress, the DMSO formation in MsrA‐treated group decreased from 162 ± 14% to 123 ± 16% (P < 0.01 vs. control shRNA with H2O2 group, Fig. 6B). We also tested the concentration of endogenous DMSO in blood and brain samples using both GC‐MS and HPLC. However, little endogenous DMSO was detected, which may be resulted by the limit of detection.