Comparison of the impact of chlordecone and its metabolite chlordecol on genes involved in pesticide metabolism in HepG2 cell line

Gulminyam Baratzhanova, Hanan EL Sheikh Saad, Agnès Fournier, Marion Huguet, Olivier Joubert, Arnaud Paul, Leyla Djansugurova, Céline Cakir‐Kiefer

2025

Full text Open access: Hybrid Metadata (CSL-JSON)

DOI 10.1016/j.etap.2025.104701

Data confidence 70 medium

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Abstract

Chlordecone (CLD) is an organochlorine pesticide that is highly resistant in the environment. This compound and its metabolite chlordecol (CLD-OH) still can be found in the French West Indies, after being banned 30 years ago. The novelty of this work lies in evaluating the toxicity of CLD-OH compared to CLD and examining the effects of these compounds on nuclear receptor (PXR, PPARα, and CAR) and metabolism-related genes (CYP2B6, CYP3A4) in vitro using HepG2 cell line as a model. Our study demonstrates that both compounds displayed an almost similar pattern of decrease in cell viability. Moreover, it was shown that CLD-OH can increase the expression of PXR, CYP3A4, and PPARα genes in comparison to CLD. The AKR1C4 gene showed a slight decrease in expression after CLD treatment. Collectively, this study provided a new finding into the impact of CLD-OH and compares the mode of action of CLD and its metabolite.