Di(2-ethylhexyl) phthalate (DEHP) is a highly harmful and persistent environmental pollutant. Due to its unique chemical composition, it frequently dissolves and enters the environment to endanger human and animal health. Lycopene is a natural bioactive component that can potentially reduce the risk of environmental factor-induced chronic diseases. The present study sought to explore the role and underlying mechanism of lycopene (LYC) on DEHP-induced renal inflammatory response and apoptosis. In this study, mice were orally treated with LYC (5 mg/kg BW/day) and/or DEHP (500 or 1000 mg/kg BW/day) for 28 days. Our results indicated that LYC prevented DEHP-induced histopathological alterations and ultrastructural injuries, including decreased mitochondrial membrane potential (ΔΨm), PINK1/Parkin pathway-mediated mitophagy, and mitochondrial energetic deficit. When damaged mitochondria release mitochondrial DNA (mtDNA) into cytosol, LYC can alleviate inflammation and apoptosis caused by DEHP exposure by activating the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) signal pathway. Collectively, our data demonstrate that LYC can reduce mitophagy caused by DEHP exposure by activating the PINK1/Parkin pathway and then reduce renal inflammation and apoptosis through the cGAS-STING pathway.
Keywords: cGAS−STING; di(2-ethylhexyl) phthalate; inflammation; lycopene; mitophagy; renal injury.