Melatonin protects against nonylphenol caused pancreatic β-cells damage through MDM2-P53-P21 axis

Nonylphenol (NP) is an endocrine disrupting chemical, which widely exists in environment and can result in multiple system dysfunction. Pancreas as one of the most important organs is sensitive to NP, while the detail toxic effect is still less studied. Previously, we unveiled nonylphenol causes pancreatic damage in rats, herein, we further explore the potential mechanism and seek protection strategy in vitro. Insulinoma (INS-1) cells exposed to NP were observed to suffer oxidative stress and mitochondrial dysfunction, as reflected by the abnormal levels of reactive oxygen species, malonic dialdehyde, superoxide dismutase, Ca²⁺, and mitochondrial membrane potential. Melatonin (MT) was found to alleviate NP-induced mitochondrial dysfunction and oxidative stress, further inhibit apoptosis and restore pancreas function. Mechanically, MT induced the MDM2-P53-P21 signaling, which upregulated the Nrf2 signaling pathway. In summary, our study clarified NP-induced INS-1 cells mitochondrial dysfunction and oxidative stress, which could be ameliorated by MT through MDM2-P53-P21 axis.