Aristolochic acid nephropathy (AAN) is a form of acute kidney injury triggered by the ingestion of aristolochic acid (AA), characterized by significant degeneration and loss of cells in the proximal tubules. Previous reports of AA-induced acute kidney injury have reported that AA-induced cytotoxicity can occur within a short period, up to 24h
however, there are few reports on the relationship between AA-DNA adduct formation and cytotoxic mechanism during the acute phase. In this study, we aimed to elucidate the toxicological mechanisms in the initial phase of AA exposure by examining the effects of AA on NRK-52E rat proximal tubular cells within 24h. We detected the formation of AA-DNA adducts as early as 4h post-exposure, indicating that 50μM of AA causes DNA damage. The DNA damage response pathway was activated, peaking at 8h post-exposure. Additionally, we observed an increasing trend of G1 phase cell cycle arrest after 8h, followed by a significant decline in cell viability at 16h. These findings suggest that 50μM of AA induces rapid DNA damage in NRK-52E cells, primarily through the formation of AA-DNA adducts, ultimately leading to G1 phase cell cycle arrest.