Endocytic inhibitors alleviate uranium-induced nephrotoxicity in HK-2 cells by reducing cellular uptake and mitigating oxidative stress and apoptosis

Uranium element possesses significant radioactivity and chemical toxicity, posing a non-negligible potential hazard to human health and ecological environment. Despite this, the toxicological mechanisms of uranium exposure remain largely not fully understood. In this study, using HK-2 cells as a model, we investigated the effects of three different endocytic inhibitors on uranium-induced toxicity and the process of uranium uptake. Our findings demonstrated a time-dependent increase in intracellular uranium content over a 2-hour period. Uranium exposure leads to a dose-dependent decrease in cell viability, along with the induction of apoptosis, oxidative stress, and mitochondrial impairment. Notably, the application of the three endocytosis inhibitors led to a reduction in cellular uranium uptake to varying extents, enhanced cell viability, increased intracellular glutathione (GSH) levels, mitigated uranium-induced oxidative stress, effectively inhibited apoptosis, reduced mitochondrial damage, and suppressed Caspase 3 activation. In conclusion, our results suggest that endocytic pathways contribute significantly to the uptake and subsequent toxicity of uranium in HK-2 cells.