Cellular responses to T-2 toxin and/or deoxynivalenol that induce cartilage damage are not specific to chondrocytes

Area of Science:

• Toxicology
• Cell Biology
• Biochemistry

Background:

• The link between T-2 toxin, deoxynivalenol (DON), and Kashin-Beck disease is debated due to unknown cartilage damage selectivity.
• Understanding the cellular and tissue-specific effects of these mycotoxins is crucial for risk assessment.

Purpose of the Study:

• To compare the cytotoxicity of T-2 toxin and DON on human chondrocytes, hepatic cells, and tubular epithelial cells.
• To investigate the distribution of T-2 toxin and DON in Sprague-Dawley rats following acute exposure.
• To elucidate the cellular mechanisms underlying the toxicity of T-2 toxin and DON.

Main Methods:

• In vitro cytotoxicity assays on C28/I2 (chondrocytes), L-02 (hepatic cells), and HK-2 (tubular epithelial cells).
• Assessment of cell proliferation, cell cycle, apoptosis, oxidative stress, and mitochondrial membrane potential.
• In vivo toxicokinetic study in Sprague-Dawley rats after single-dose exposure to T-2 toxin and DON.

Main Results:

• T-2 toxin and DON reduced cell proliferation in a time- and concentration-dependent manner, with an antagonistic effect in combination.
• Both toxins induced cell cycle arrest and apoptosis, increased oxidative stress, and decreased mitochondrial membrane potential.
• In vivo, T-2 toxin and DON did not accumulate preferentially in knee joints compared to liver and kidney.

Conclusions:

• T-2 toxin and DON inhibit proliferation and induce apoptosis through a reactive oxygen species-mediated mitochondrial pathway.
• The observed toxicity mechanisms are not specific to chondrocytes in vitro or joint tissues in vivo.
• These findings suggest a broader systemic toxicity rather than a specific chondrotoxic effect of T-2 toxin and DON.