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

Abstract

Deoxynivalenol (DON) and T‐2 toxin are prevalent mycotoxin contaminants in the food and feed stuffs worldwide, with non‐negligible co‐contamination and co‐exposure conditions. Meanwhile, they are considerable risk factors for Kashin‐Beck disease, a chronic endemic osteochondropathy. The aim of this study was to investigate the individual and combined cytotoxicity of DON and T‐2 toxin on proliferating human C‐28/I2 and newborn rat primary costal chondrocytes by MTT assay. Four molar concentration combination ratios of DON and T‐2 toxin were used, 1:1 for R1 mixture, 10:1 for R10, 100:1 for R100 and 1000:1 for R1000. The toxicological interactions were quantified by the MixLow method. DON, T‐2 toxin, and their mixtures all showed a clear dose‐dependent toxicity for chondrocytes. The cytotoxicity of T‐2 toxin was 285‐fold higher than DON was in human chondrocytes, and 22‐fold higher in the rat chondrocytes. The combination of DON and T‐2 toxin was significantly synergistic at middle and high level concentrations of R10 mixtures in rat chondrocytes, but significantly antagonistic at the low concentrations of R100 mixtures in both cells and at the middle concentrations of R1000 mixtures in rat chondrocytes. These results indicated that the combined toxicity was influenced by the cell sensitivity for toxins, the difference between the combination ratio and equitoxic ratio, the concentrations and other factors.

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

“…The authors explained this interaction by the competition between the mycotoxins for the same target/receptor site [14,19]. Lin et al [92] suggested that the effect of DON and T-2 is additive/synergistic at middle and high concentrations but antagonistic at low concentrations in rat chondrocytes and C-28/I2 cells. Additionally, synergic effect was also detected when the individual levels were at nearly the same ratio and antagonistic effect when the concentration of DON was much higher (100-1000×) than T-2 [92].…”

Assessment of urinary biomarkers of mycotoxin exposure in adults from Cameroon

“…One urine sample contained only one mycotoxin, while 20 combinations of two or up to seven mycotoxin urinary biomarkers were observed; more than 70% of the urines contained ve or more different mycotoxins. Complex mixture toxicology remains poorly examined though several groups have recently examined combined effects in vitro [47,48,49,50,51,52,53,54,55,56,57,44,45], with animal studies being more limited [58,59]. These studies remain hard to interpret for public health decisions, but some suggest more than additive effects, thus the mixtures reported here and elsewhere highlight signi cant knowledge gaps.…”

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

“…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, ). Therefore, these findings highlight the adverse effects of DON on chondrocyte that may be involved in the development of KBD.…”

“…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.…”