Methyl and propylparaben elicit distinct thyroid-disrupting effects in a rat thyroid cell model

Parabens, including methylparaben (MtP) and propylparaben (PrP), are synthetic preservatives commonly used in cosmetics and personal care products. Increasing evidence suggests that these compounds may act as endocrine-disrupting chemicals (EDCs), but their effects on thyroid function remain incompletely understood. This study aimed to investigate the impact of MtP and PrP on cell viability, proliferation, oxidative stress, thyroid-related gene expression, genotoxicity, and effects on cAMP in differentiated FRTL-5 rat thyroid cells. FRTL-5 cells were treated with MtP or PrP at concentrations of 0, 0.001, 0.01, 0.1, 1, 10, and 100 μg/ml for 24, 48, and 72 hours. Cell viability and proliferation were assessed by WST-1 and crystal violet assays, respectively. Reactive oxygen species (ROS) generation was measured using a DCFDA-based fluorescence assay. Gene expression of thyroid-related genes ( TG , TSHR , NIS , NKX2-1 , PAX8 , TPO ) was quantified by real-time PCR. Micronuclei formation was evaluated as a marker of genotoxicity. Intracellular cAMP levels were measured using an ELISA-based method. PrP at 100 μg/ml significantly reduced cell viability (after 72 hours) and proliferation (after 48–72 hours) at difference with MtP. Both PrP 100 μg/ml and MtP 10–100 μg/ml increased ROS levels. PrP and MtP induced complex, dose-dependent, and non-monotonic changes in gene expression. Notably, PrP 10 μg/ml upregulated most thyroid-related genes, while PrP 100 μg/ml suppressed them. cAMP levels increased significantly with PrP 100 μg/ml. No significant genotoxicity was observed. In conclusion, MtP and PrP exert different effects on thyroid cells, supporting their potential role as thyroid-disrupting chemicals.