Repeated pyrocatechol exposure induces persistent oxidative stress resistance associated with Nrf2 activation in HepG2 cells

Cells adapt to oxidative stress by activating inducible antioxidant defense systems, among which the Nrf2 signaling pathway plays a central role. Pyrocatechol, a phenolic compound generated during coffee roasting, has been reported to activate Nrf2 signaling; however, whether repeated exposure to pyrocatechol induces a persistent adaptive cytoprotective response to oxidative stress in hepatic cells remains unclear. In this study, we examined whether repeated daily exposure to pyrocatechol enhances resistance to subsequent oxidative stress in HepG2 cells. Repeated pyrocatechol treatment for 6 days promoted Nrf2 nuclear translocation together with increased HO-1 expression and enhanced resistance to subsequent H₂O₂-induced oxidative stress. In short-term experiments, brusatol suppressed HO-1 induction and attenuated the cytoprotective effect of a single pyrocatechol treatment, supporting the involvement of Nrf2 signaling. Notably, enhanced resistance to H₂O₂ persisted after pyrocatechol removal and cell reseeding, indicating that repeated pyrocatechol exposure induces a persistent adaptive cytoprotective response in HepG2 cells.