Determination of the mechanisms of hepatotoxicity induced by chlordecone and chlordecol from HepaRG cells and proteomic analyzes

Chlordecone (CLD) is a pesticide used to control the banana weevill in the French West Indies from 1970 to 1993. Despite its ban in the 90s, the highly persistence of CLD and contamination of the food webs raised tremendous concern for public health [1]. CLD can induce reprotoxic, neurotoxic and hepatotoxic effects in humans and is involved in prostate cancer [2] and liver fibrosis potentiation [3]. In liver, although CLD is metabolized into phase I metabolite chlordecol (CLD-OH), it is highly biopersistent. Nevertheless, the cellular hepatic effects of these 2 compounds have been poorly described. Therefore, we used an original approach to investigate in vitro toxicity responses of CLD and CLD-OH in liver cell models (HepaRG cells and primary human hepatocytes, PHHs) using metabolomics and proteomics. 1) Resiere, D., et al. (2023). Chlordecone (Kepone) poisoning in the French Territories in the Americas. Lancet 401, 916. 2) Multigner L., et al. (2010). Chlordecone exposure and risk of prostate cancer. J Clin Oncol 28, 3457-3462. 3) Tabet E., et al. (2016). Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice. Toxicol Lett 255, 1-10.