Association of F-53B Nephrotoxicity with Oxidative Stress-Mediated Mitochondrial Dysfunction and Altered Autophagy-Apoptosis Crosstalk.

Authors

Bitong Li, Dongling Liu, Zhiying Qiu, Yaojian Zheng, Yue Wu, Lina Zhang, Ran Li, Cuiqing Liu, Qinghua Sun, Xiang Zeng

Published in

Biomolecules. Volume 16. Issue 7. Jun 24, 2026. Epub Jun 24, 2026.

Abstract

6:2 chlorinated polyfluorinated ether sulfonate (F-53B, also known as 6:2 Cl-PFESA) is a major alternative to perfluorooctane sulfonate (PFOS) and a widespread environmental pollutant with potential public health hazards. However, its nephrotoxic effects and underlying molecular mechanisms remain poorly understood. This study investigated renal injury induced by environmentally relevant concentrations of F-53B and delineated the mechanistic cascade using a mouse model combined with quantitative proteomic and molecular biological approaches. Male C57BL/6 mice were exposed to 0, 4, 40, and 400 μg/L F-53B for 4 weeks. F-53B exposure led to significant renal dysfunction, histopathological damage, elevated renal injury biomarkers, and pronounced oxidative stress in a dose-dependent manner. A proteomic comparison of the 0 μg/L versus 400 μg/L groups identified 276 differentially expressed proteins that were strongly enriched in oxidative phosphorylation, autophagy, and apoptosis pathways, with cytochrome c oxidase subunit 7b (Cox7b) serving as a core downregulated hub molecule. Further validation confirmed that F-53B triggered overt mitochondrial structural damage, impaired respiratory chain complex assembly, aberrant ATP production, and disturbed mitochondrial dynamics. Consequently, excessive autophagy activation and mitochondrial-mediated apoptosis were simultaneously stimulated in renal tissues. Notably, although statistically significant, the alterations induced by F-53B were generally mild in magnitude. Collectively, our findings demonstrate that F-53B induces nephrotoxicity through a sequential pathological cascade. This study provides novel mechanistic insights into F-53B-elicited renal injury and highlights the potential health risks of this emerging per- and polyfluoroalkyl substance (PFAS) alternative.

PMID:
42509732
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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