2. Academic Validation
  3. Chondroitin sulfate A-selenium nanoparticles protect chondrocytes from T-2 toxin-induced oxidative stress and mitochondrial dysfunction through activating autophagy by the SIRT1-AMPK-FOXO3 pathway

Chondroitin sulfate A-selenium nanoparticles protect chondrocytes from T-2 toxin-induced oxidative stress and mitochondrial dysfunction through activating autophagy by the SIRT1-AMPK-FOXO3 pathway

  • Ecotoxicol Environ Saf. 2025 Sep 15:303:118797. doi: 10.1016/j.ecoenv.2025.118797.
Huan Deng 1,  Jinyan Lin 2,  Yude Jiang 3,  Abebe Feyissa Amhare 4,  Lichun Qiao 5,  Jun Wang 6,  Jing Han 7
Affiliations

Affiliations

  • 1 Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China; Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710049, China; Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
  • 2 Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710049, China; Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
  • 3 Department of Nutrition,Western Theater Command Air Force Hospital of PLA, Chengdu, Sichuan 610083, China. Electronic address: [email protected].
  • 4 Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710049, China; Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
  • 5 Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710049, China; Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
  • 6 Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China. Electronic address: [email protected].
  • 7 Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 712000, China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, Shaanxi 710049, China; Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
PMID: 40763514 DOI: 10.1016/j.ecoenv.2025.118797
Abstract

T-2 toxin is known to cause tissue and cellular damage, with chondrocytes being particularly vulnerable. In contrast, chondroitin sulfate A-selenium nanoparticles (CSA-SeNP) have shown cartilage-protective properties, although the precise molecular mechanism remains incompletely elucidated. This study used T-2 toxin and CSA-SeNP to treat human C28/I2 chondrocytes, and studied their effects on SIRT1-AMPK-FOXO3 pathway and oxidative damage, mitochondrial dysfunction, impaired Autophagy, and Apoptosis. Autophagy was evaluated by acridine orange (AO) and dansylcadaverine (MDC) staining, transmission electron microscopy observation, and mRFP-GFP-LC3 adenovirus. Oxidative stress (ROS, MDA, SOD, CAT, T-AOC) and mitochondrial function (ATP, SDH, ATPases, membrane potential) were assessed. Western blotting analyzed the expression level of the SIRT1-AMPK-FOXO3 pathway, Autophagy markers, and Apoptosis. We found that 4-hour exposure to 5 and 20 ng/mL, as well as 12-hour exposure to 5 ng/mL of T-2 toxin, activated the SIRT1-AMPK-FOXO3 pathway compensatively, inducing Autophagy but inhibiting degradation of autolysosome, leading to oxidative damage, mitochondrial dysfunction, and increased Apoptosis. 12-hour exposure to 20 ng/mL T-2 toxin inhibited this pathway and Autophagy, causing serious damage to chondrocytes. CSA-SeNP alleviated the inhibition of the SIRT1-AMPK-FOXO3 pathway induced by T-2 toxin, reducing oxidative damage, mitochondrial dysfunction and Apoptosis, thereby restoring Autophagy to protect chondrocytes. In summary, T-2 toxin's effects on chondrocyte Autophagy were dose- and time-dependent. CSA-SeNP protected against T-2 toxin by activating the SIRT1-AMPK-FOXO3 pathway, suggesting its potential for chondrocyte protection. This study may provide new insights into the development of T-2 toxin detoxification strategies and the method for prevention and treatment of chondrocyte damage.

Keywords

Autophagy; Chondroitin sulfate A‑selenium nanoparticles; Mitochondrial dysfunction; Oxidative stress; SIRT1-AMPK-FOXO3 pathway; T-2 toxin.

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