GSH promote renal cadmium efflux through ABCC1 of ABC family.

Accumulation of cadmium in the kidneys can lead to toxicity; therefore, it is crucial to identify methods that promote cadmium excretion to mitigate nephrotoxicity. However, the mechanisms underlying cadmium excretion from the kidneys remain unclear. The role of the ATP-binding cassette (ABC) transporter family in the renal excretion of cadmium was investigated in this study. We employed gene chip technology to identify alterations in gene and protein expression within the ABC transporter family, particularly focusing on ABCC1, in response to cadmium exposure. Utilizing CRISPR-Cas9 technology, we created NRK cells that overexpress ABCC1 (LV-OE), and observed that the overexpression of ABCC1 accelerated cadmium efflux in these cells. Conversely, the application of an ABCC1 inhibitor (MK571) to NRK cells suppressed ABCC1 expression and delayed cadmium efflux. Molecular docking studies, informed by computer-aided drug design, indicated that glutathione (GSH) exhibits a superior binding affinity to the ABCC1 protein structure. Furthermore, the addition of GSH enhanced cadmium efflux from renal tissue and NRK cells, suggesting that cadmium efflux may be mediated by the ABCC1 protein. These findings imply that ABCC1 plays a significant role in facilitating cadmium efflux in the kidneys, and that GSH can enhance this process via ABCC1. This research offers new targets and potential therapeutic strategies to address cadmium-induced nephrotoxicity.