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

Abstract

The relationship between T-2 toxin and deoxynivalenol (DON) and the risk of Kashin-Beck disease is still controversial since it is poorly known about their selectivity in cartilage damage. We aimed to compare the cytotoxicity of T-2 toxin and DON on cell lines representative of cell types encountered in vivo, including human chondrocytes (C28/I2), human hepatic epithelial cells (L-02) and human tubular epithelial cells (HK-2). In addition, we determined the distribution of T-2 toxin and DON in Sprague-Dawley (SD) rats after a single dose exposure. T-2 toxin or DON decreased proliferation in a time- and concentration-dependent manner and their combination showed a similar antagonistic effect in C28/I2, L-02 and HK-2 cells. Moreover, we observed cell cycle arrest and apoptosis, associated with increased oxidative stress and decline in mitochondrial membrane potential induced by T-2 toxin and/or DON. In vivo study showed that T-2 toxin and DON did not accumulate preferentially in the knee joint compared to liver and kidney after an acute exposure in SD rats. These results suggest that T-2 toxin and/or DON inhibit proliferation and induce apoptosis through a possible mechanism involving reactive oxygen species-mediated mitochondrial pathway that is not specific for chondrocytes in vitro or joint tissues in vivo.

Inhibiting the aberrant activation of Wnt/β‐catenin signaling by selenium supplementation ameliorates deoxynivalenol‐induced toxicity and catabolism in chondrocytes

“…In the current study, we isolated human articular chondrocytes and corroborated that DON treatment suppressed cell proliferation and LDH release, a marker of necrosis degree. Analogously to previous research (Y. Lei et al, ), DON exposure induced cell apoptosis, concomitant with increased activities of caspase‐3 and caspase‐9. Accordingly, excessive chondrocyte apoptosis is extensively studied as a contributing factor to the pathology of KBD (Lin et al, ; H. J. Yang et al, ; L. Yang, ).…”

“…Excessive chondrocyte apoptosis is accepted as a primary pathological contributor to KBD. Recently, it was demonstrated that exposure to DON has been reported to induce cell apoptosis, oxidative stress, and cell cycle arrest in human C28/12 chondrocyte line (Y. Lei et al, ; Lin et al, ). However, the effects and underlying mechanism of DON in the development of KBD remain unclear.…”

T-2 mycotoxin induced apoptosis in broiler’s liver tissue

“…The induction of apoptosis of T-2 toxin through a possible mechanism involving reactive oxygen species-mediated mitochondrial pathway is also supported by other authors [13].…”

Individual and combined toxicity of T‐2 toxin and deoxynivalenol on human C‐28/I2 and rat primary chondrocytes

“…During yeast bioassay, the molar concentration combination ratio of DON + T‐2 between 787:1 and 6298:1 revealed antagonistic interactions (Koshinsky & Khachatourians, ). The antagonistic effects were also indicated by the mixture of DON and T‐2 toxin at the molar concentration combination ratio 40:1 on CHO‐K1 cells (Ruiz, Franzova, et al, ), 63:1 on C‐28/I2, HK‐2 and L‐02 cells (Lei et al, ), 160:1 on Vero cells (Ruiz, Macakova, et al, ) and 250:1 on the human lymphocyte (Thuvander et al, ). Details of the literature are listed in Supporting information Table S1.…”

“…Serial dilutions of DON interacted antagonistically with T‐2 toxin in a bioassay with yeast Kluyveromyces marxianus (Koshinsky & Khachatourians, ). The combination of DON and T‐2 toxin resulted in inhibition slightly lower than expected in the human lymphocyte proliferation test (Thuvander, Wikman, & Gadhasson, ), while the combination of DON and T‐2 toxin presented antagonistic effects in Vero and CHO‐K1 cells (Ruiz, Franzova, et al, , Ruiz, Macakova, et al, ), and in C28/I2, L‐02 and HK‐2 cells (Lei et al, ). The combination of DON and T‐2 toxin produced also additive or synergic myelotoxic effects on human granulo‐monocytic hematopoietic progenitors (Ficheux, Sibiril, & Parent‐Massin, ).…”