Butylated hydroxyanisole (BHA) is a widely used antioxidant for food preservation. 11β-hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2) have been demonstrated to be the regulators of the local level of active glucocorticoid, which has a broad range of physiological actions. In this study, the potency of BHA was tested for the inhibition of HSD11B1 and HSD11B2 in rat and human tissues. BHA showed potent inhibition of HSD11B2 with the half maximal inhibitory concentration calculated at 13.99 and 69.25 µmol/l for the rat and human, respectively. Results showed that BHA competitively inhibited HSD11B2 when a steroid substrate was used. However, it served as a mixed inhibition factor when the cofactor NAD+ was used. In contrast, the potency of BHA to inhibit both rat and human HSD11B1 was diminished, with the concentration of 100 μmol/l causing no inhibitory effect on the isoform. In conclusion, we observed that BHA is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as kidney and placentas.
© 2015 S. Karger AG, Basel.