The mechanisms of acute kidney injury and chronic kidney disease remain incompletely revealed, and drug development is a pressing clinical challenge. Oxidative stress-induced cellular senescence and mitochondrial damage are important biological events in a variety of kidney diseases. As a type of carotenoid, β-Cryptoxanthin (BCX) has various biological functions, which means it is a potential therapeutic candidate for the treatment of kidney disease. However, the role of BCX in the kidney is unclear, and the effect of BCX on oxidative stress and cellular senescence in renal cells is also unknown. Therefore, we conducted a series of studies on human renal tubular epithelial (HK-2) cells in vitro. In the present study, we investigated the effect of BCX pretreatment on H2O2-induced oxidative stress and cellular senescence and explored the potential mechanism of BCX action. The results showed that BCX attenuated H2O2-induced oxidative stress and cellular senescence in HK-2 cells. Moreover, BCX promoted NRF2 nuclear expression, maintained mitochondrial function, and reduced mitochondrial damage in HK-2 cells. In addition, silencing NRF2 altered the protective effect of BCX on mitochondria and significantly reversed the anti-oxidative stress and anti-senescence effects of BCX in HK-2 cells. We concluded that BCX maintained mitochondrial function by promoting NRF2 nuclear translocation to inhibit oxidative stress-induced senescence in HK-2 cells. In light of these findings, the application of BCX might be a promising strategy for the prevention and treatment of kidney diseases.
Keywords: HK-2 cells; NRF2; oxidative stress; senescence; β-Cryptoxanthin.