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.

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.