Significant contribution of autophagy in mitigating cytotoxicity of gadolinium ions.

Gadolinium-based contrast agents (GBCAs) are widely used in clinical magnetic resonance imaging (MRI). Free gadolinium ions (Gd) released from GBCAs potentially increase the risk of GBCA-related toxicity. However, the cellular responses to Gd and the underlying mechanisms responsible for protection against Gd remain poorly understood. Recently, autophagy has been considered a cell survival mechanism against various toxic metals. Here, we investigated the relationship between Gd and autophagy, as well as the effect of autophagy inhibition on the survival of cells exposed to Gd. We found that the increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, a marker protein of autophagy, in Gd-exposed human embryonic kidney 293 (HEK293) cells. Moreover, we found a greater accumulation of LC3-II after exposure to an autophagy inhibitor, chloroquine (CQ), combined with Gd than that after exposure to CQ alone, suggesting that Gd activated autophagy in HEK293 cells. Furthermore, we found that Gd reduced cell viability, which was more pronounced after CQ treatment. Our findings indicated that autophagy exerted a cytoprotective effect against Gd toxicity, suggesting a potential link between autophagy and GBCA-associated adverse events.