Medium-chain chlorinated paraffins (MCCPs) induce renal cell aging and ferroptosis

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PURPOSE: Medium-chained chlorinated paraffins (MCCPs) are a class of chlorinated derivatives of straight-chain n-alkanes with complex compositions, which are widely used in industry. The chlorinated paraffins (CPs) are divided into short chain chlorinated paraffins (SCCPs), medium chain chlorinated paraffins (MCCPs) and long chain chlorinated paraffins (LCCPs). SCCPs have been banned due to their severe bioaccumulation and biotoxicity. Therefore, MCCPs are used as a substitute for SCCPs. However, the toxicological data of MCCPs are still very limited. For this, we systematically investigated the toxicological impact of MCCPs on a renal cell model in the current study. Our work provides basic research data for analyzing the toxicological effects of MCCPs, suggesting that MCCPs should be restricted in their usage. METHOD: A series of biochemical experiments was performed, including Western blot, indirect immunofluorescence assay, and ELISA was performed to analyze the toxicological effects of MCCPs. RESULTS: Two renal cell lines were used as a model for assessing the toxicological effects of MCCPs. Cell proliferation assays showed that MCCPs could inhibit the proliferation of kidney cells in a dose-dependent manner. Further studies showed that MCCPs induced ferroptosis in kidney cells by evaluating a series of ferroptosis marker molecules. Additionally, MCCPs induced inflammatory response and premature senescence in HEK293 and NRK-52E cells. Molecular mechanism experiments showed that ferroptosis induced by MCCPs emerged as a significant contributor to premature aging of kidney cells. CONCLUSION: The current study provides basic research data to analyze the toxicological effects of MCCPs and their toxicity mechanisms. It also provides a theoretical basis for the assessment of the potential ecological risk of MCCPs, as well as basic experimental data for the rational and standardized use of MCCPs.

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