Fusariotoxin-Induced Toxicity in Mesenchymal Stem Cells and Fibroblasts: A Comparison Between Differentiated and Undifferentiated Cells

Shikhaliyeva I., Kığ C., Gömeç Ö. Y., Albayrak G.

TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES, cilt.0, sa.0, 2023 (ESCI)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 0 Sayı: 0
  • Basım Tarihi: 2023
  • Doi Numarası: 10.4274/tjps.galenos.2023.76128
  • Dergi Adı: TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, TR DİZİN (ULAKBİM)
  • İstanbul Üniversitesi Adresli: Evet

Özet

Introduction: Humans are unknowingly exposed to mycotoxins through the consumption of plant-derived foods and processed products contaminated with these toxic compounds. In addition to agricultural losses, Fusarium toxins have been shown to pose a threat to human health as well. However, the effects of fusariotoxins on the viability and proliferation of stem cells have not been fully explored. We aimed to investigate the cytotoxic effects of deoxynivalenol and B-trichothecene mix on mesenchymal stem cells and L929 fibroblast cell line.

Methods: Mesenchymal stem cells were isolated from dental pulp tissue. Doubling time and viability of dental pulp stem cells (DPSCs) and L929 cells were determined by MTT assay. The following doses of Btrichothecenes (0.25-16 µg/mL; 24 h and 48 h) were used for evaluating cytotoxicity. Also, changes in the confluency-dependent response of DPSCs to deoxynivalenol toxicity were determined. Moreover, we investigated the effect of deoxynivalenol on cell death via AO/EB double staining.

Results: Deoxynivalenol and B-trichothecene mix, showed a dose- and time-dependent inhibitory effect on the proliferation of both cells. DPSCs exposed to DON for 48 h (IC50 =0.5 µg/mL) were found to be 16 folds more sensitive than the L929 cells (IC50 = 8 µg/mL). When compared to a culture with 80% confluency, DPSCs from a 50% confluent culture were more sensitive to varying doses of DON (0.25-4 µg/mL, 24-48 h). Moreover, AO/EB staining showed that treatment of DPSCs with DON led to a significant increase in cell death (17% for 2.4 µg/mL; 50% for 4.8 µg/mL).

Discussion and Conclusion: This study reveals that undifferentiated mesenchymal stem cells are significantly more sensitive to DON in comparison to differentiated somatic cells (L929). Given the fact that humans are frequently exposed to these mycotoxins, our findings imply that prolonged exposure to them may also have harmful effects on cellular differentiation and embryonic development.