Associate Professor Xiang Zeng
School of Public Health, Zhejiang Chinese Medical University, China
Title: MitoQ Alleviates F-53B-Induced Nephrotoxicity: Mechanistic Verification in Mice Experiment and Implications from NHANES-Based PFAS Population Analysis
Abstract:
Background: 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a PFAS used as a PFOS replacement in electroplating, is widely detected in Chinese environmental matrices and human serum. F-53B triggers nephrotoxicity via oxidative-stress-driven mitochondrial injury and dysregulated autophagy-apoptosis crosstalk, yet intervention strategies remain lacking. Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, can mitigate organ damage by scavenging mitochondrial reactive oxygen species (mtROS). This study examined associations between PFAS exposure and human renal impairment using national population data, and tested whether MitoQ alleviates F-53B-induced kidney impairment in mice.
Methods: We performed linear and logistic regression on NHANES 2003–2018 data (n = 10,314) to evaluate relationships between serum PFAS and renal outcomes (eGFR, renal impairment, chronic kidney disease). In a 4-week mouse model, male C57BL/6 mice were divided into control, MitoQ-only, F-53B-exposed, and F-53B + MitoQ groups. We assessed renal histopathology, serum biochemistry, oxidative stress, mitochondrial ultrastructure, energy metabolism, and autophagy-apoptosis signaling.
Results: Higher PFAS concentrations correlated with reduced eGFR (β = −0.60; 95%CI: −1.04, −0.17; P = 0.007) and elevated odds of renal impairment (OR = 1.11; 95%CI: 1.04, 1.19; P = 0.003). In mice, F-53B caused tubular-glomerular lesions, mtROS overproduction, mitochondrial structural and bioenergetic defects, and excessive autophagy and apoptosis. MitoQ scavenged mtROS, restored mitochondrial homeostasis, inhibited STK11/AMPK-mediated autophagy hyperactivation, and suppressed Bax/Bak-dependent tubular cell death, ameliorating kidney damage.
Conclusion: Combined population and animal evidence supports that mtROS overaccumulation drives F-53B-related nephrotoxicity. MitoQ confers multi-layered renal protection, providing pre-clinical evidence for mitigating kidney risks in populations exposed to PFAS alternatives. Limitations include absence of human F-53B measurements in NHANES and single-dose short-term animal exposure.
Keywords: F-53B; PFOS alternative; Mitochondrial targeted antioxidant; MitoQ; nephrotoxicity; Renal injury intervention
Biography:
Dr. Xiang Zeng is an Associate Professor and Master's Supervisor at the School of Public Health, Zhejiang Chinese Medical University, where he also serves as Director of the Department of Climate Change and Health. He received his PhD in Epidemiology from the University of Groningen, the Netherlands, in 2016 and was awarded the Outstanding Postdoctoral Fellowship of Jinan University in 2021. His research focuses on environmental exposure (e-waste, climate change, air pollution, and plastic tableware leachates) and health effects, with particular emphasis on the molecular toxicity mechanisms of environmental pollutants and their prevention and treatment. He has served as Principal Investigator of multiple projects, including a China Postdoctoral Science Foundation General Program and a Guangdong Pearl River Talent Plan Overseas Young Talents Program. He has published over 50 papers, including more than 30 as first or corresponding author in journals such as Journal of Hazardous Materials, Environment International, Environmental Pollution, Ecotoxicology and Environmental Safety, and Environmental Health. He serves as an editor for BMC Cardiovascular Disorders, Toxicology Advances, and Medical Animal Prevention and Control, and is a member of the International Society for Heart Research and the Chinese Society of Toxicology.