Benzyl isothiocyanate ameliorates acetaldehyde-induced cytotoxicity by enhancing aldehyde dehydrogenase activity in murine hepatoma Hepa1c1c7 cells

- Benzyl isothiocyanate (BITC) significantly increased the total aldehyde dehydrogenase (ALDH) activity.
- BITC activated the gene expression of ALDHs.
- BITC stimulated the nuclear translocation of Nrf2.
- Silencing Nrf2 inhibited the total ALDH activity as well as ALDH gene expression.
- BITC mitigated the acetaldehyde-induced cytotoxicity through the Nrf2-dependent pathway.

In the present study, we assessed benzyl isothiocyanate (BITC), an organosulfur compound from cruciferous vegetables, as a potential inducer of aldehyde dehydrogenase (ALDH) activity using murine hepatoma Hepa1c1c7 cells. BITC was shown to enhance not only the total ALDH activity, but also the ALDH activity of the cytosolic/microsomal and mitochondrial fraction. BITC also significantly increased the gene and protein expression of ALDH1A1, ALDH2 and ALDH3A1 in a concentration-dependent manner. Simultaneously, the gene expression of phase 2 drug-metabolizing enzymes, such as NAD(P)H: quinone oxidoreductase 1 and heme oxygenase-1, was increased by the BITC treatment. Western blot experiments revealed that BITC not only up-regulated the Nrf2 protein expression, but also stimulated the nuclear translocation of Nrf2. Furthermore, silencing Nrf2 reduced the basal and BITC-enhanced levels of the total activity and gene expression of ALDHs. The pretreatment of BITC completely mitigated the acetaldehyde-induced cytotoxicity, which was impaired by silencing Nrf2. The present study demonstrated that BITC has been identified as a potential inducer of the total ALDH activity to prevent the acetaldehyde-induced cytotoxicity.

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