DBP and BaP co-exposure induces kidney injury via promoting pyroptosis of renal tubular epithelial cells in rats

Dibutyl phthalate (DBP) and benzo(a)pyrene (BaP) are widespread environmental and foodborne contaminants that have detrimental effects on human health. Although people are often simultaneously exposed to DBP and BaP via the intake of polluted food and water, the combined effects on the kidney and potential mechanisms remain unclear. Hence, we treated rats with DBP and BaP for 90 days to investigate their effects on kidney histopathology and function. We also investigated the levels of paramount proteins and genes involved in pyroptosis and TLR4/NF-κB p65 signaling in the kidney. Our research showed that combined exposure to DBP and BaP triggered more severe histopathological and renal function abnormalities than in those exposed to DBP or BaP alone. Simultaneously, combined exposure to DBP and BaP enhanced the excretion of IL-1β and IL-18, along with the release of LDH in rat renal tubular epithelial cells (RTECs). Moreover, combined exposure to DBP and BaP increased the expression of pyroptosis marker molecules, including NLRP3, ASC, cleaved-Caspase-1, and GSDMD. Meanwhile, the combination of DBP and BaP activated TLR4/NF-κB signaling in the kidney. Taken together, the combined exposure to DBP and BaP causes more severe kidney injury than that caused by DBP or BaP exposure separately. In addition, pyroptosis of RTECs regulated by TLR4/NF-κB signaling may add to the kidney damage triggered by combined exposure to DBP and BaP.