Lycopene ameliorates DEHP exposure-induced renal pyroptosis through the Nrf2/Keap-1/NLRP3/Caspase-1 axis

Di (2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in plastic products, and due to its unique chemical composition, it frequently dissolves and enters the environment. Lycopene as a natural carotenoid has been shown to have powerful antioxidant capacity and strong kidney protection. This study aimed to investigate the role of the interplay between oxidative stress and the classical pyroptosis pathway in LYC alleviating DEHP-induced renal injury. ICR mice were given DEHP (500 mg/kg/d or 1000 mg/kg/d) and/or LYC (5 mg/kg/d) for 28 days to explore the underlying mechanisms of this hypothesis. Our results indicated that DEHP caused the shedding of renal tubular epithelial cells, increased the content of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the tissue, the decrease of antioxidant activity markers and the increase of oxidative stress indexes. It is gratifying that LYC alleviates DEHP-induced renal injury. The expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) and its downstream target genes is improved in DEHP induced renal injury through LYC mediated protection. Meanwhile, LYC supplementation can inhibit DEHP-induced Caspase-1/NLRP3-dependent pyroptosis and inflammatory responses. Taken together, DEHP administration resulted in nephrotoxicity, but these changes ameliorated by LYC may through crosstalk between the Nrf2/Keap-1/NLRP3/Caspase-1 pathway. Our study provides new evidence that LYC protects against kidney injury caused by DEHP.