Comparative study of thyroid damaging effects of 6：2 polyfluoroalkyl phosphate diester in rats and mice via the Keap1/Nrf2/HO-1 pathway

Abstract

Abstract:

Objective To investigate thyroid damage in rats and mice exposed to different doses of 6：2 polyfluoroalkyl phosphate diester（6：2diPAP），explore the effects of 6：2diPAP on thyroid dysfunction and oxidative stress and the possible mechanisms. Methods Fifteen female SD rats and 15 female C57BL/6 mice were randomly divided into a blank control group，a solvent control group，and a 6：2 diPAP low，medium，and high exposure group（0.5，5.0 and 50.0 μg/kg），with three mice in each group，and were dyed by gavage for 21 days. The levels of free triiodothyronine（FT3），free thyroxine（FT4），and thyrotropin（TSH） in serum were measured by enzyme-linked immunosorbnent assay（ELISA），and the activities of superoxide dismutase（SOD） and catalase（CAT） and the content of malondialdehyde（MDA） in thyroid tissues were determined by chemical assay kits，and the possible mechanism of action of thyroid damage caused by the exposure of 6：2diPAP was investigated using Western blot assay. Results Exposure to 6：2diPAP caused thyroid dysfunction in rats and mice. The ELISA results showed that，compared to the control and solvent control groups，high exposure to 6：2diPAP decreased serum levels of FT3[（5.49±0.70）pg/mL] and FT4[（8.66±0.43）pg/mL]，and increased TSH[（9.13±1.33）ng/mL] levels in rats（P<0.05）. In mice，no statistically significant differences were observed in these hormone indicators（P>0.05）.Further analysis showed that high exposure to 6∶2diPAP significantly inhibited SOD[（82.49±4.27）U/mgprot] and CAT[（1.26±0.19）U/mgprot] activities and led to increased MDA[（2.34±0.24）μmol/gprot] concentrations in rat thyroid tissue（P<0.05）. In mice，SOD[（13.90±1.48）U/mgprot] and CAT[（9.72±1.14）U/mgprot] showed a downward trend and MDA[（2.15±0.10）μmol/gprot] showed an upward trend，but the differences were not statistically significant（P>0.05）. Western blot results showed that 6∶2diPAP high exposure significantly down-regulated the expression levels of kelch-like ECH-associated protein 1（Keap1）（0.73±0.12），nuclear factor E2-related factor 2（Nrf2）（0.60±0.29），and heme oxygenase-1 （HO-1）（0.66±0.07） proteins in the thyroid tissues of rats（P<0.05）.Nrf2（0.55±0.27） protein expression in mouse thyroid tissue was also significantly decreased（P<0.05）. Conclusions 6∶2diPAP exposure may trigger thyroid dysfunction by stimulating oxidative stress，with rats showing greater sensitivity. The underlying mechanism of action may be related to the suppression of the Keap1/Nrf2/HO-1 antioxidant defense pathway and a consequent reduction in antioxidant capacity.

Key words: Polyfluoroalkyl phosphate diesters, Thyroid injury, Thyroid hormones, Oxidative stress, Keap1/Nrf2/HO-1 pathway

CLC Number:

R-332

ZHANG Xinxuan, QI Xinxin, CONG Meili, LIU Jincun, SUN Hongguang, LIU Tao. Comparative study of thyroid damaging effects of 6：2 polyfluoroalkyl phosphate diester in rats and mice via the Keap1/Nrf2/HO-1 pathway. [J]OCCUPATION AND HEALTH, 2026, 42(8): 1057-1064.

Figures/Tables 5

References 30

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