Human myelotoxicity of two phycotoxins, okadaic acid and domoic acid. An in vitro study

Abstract

Okadaic acid (OA), a diarrheic shellfish toxin and domoic acid (DA), an amnesic shellfish toxin are phycotoxins produced by various species of microalgaes. The aim of this study was to explore the effects of OA and DA on hematopoietic progenitors. For this purpose, three lineages of human hematopoietic progenitors, CFU-GM, BFU-E and CFU-MK optimized for toxicological studies were used. The effects of OA and DA on cell precursor proliferation and differentiation were investigated at concentration from 0.5 to 25 ng mL⁻¹ and from 0.1 to 100 µg mL⁻¹, respectively. A study of concentration and effect relationship showed a cytotoxic effect of OA (25 ng mL⁻¹) for human hematopoietic progenitors. Moreover, this phycotoxin inhibited erythroid progenitors proliferation and disturbed differentiation at concentrations of 5 ng mL⁻¹ and higher. OA IC₅₀ were determined at 7.5 ng mL⁻¹, 7.54 ng mL⁻¹ and 1.19 ng mL⁻¹ for CFU-GM, BFU-E and CFU-MK, respectively. Cytotoxic effects of OA and DA were compared to those effect of trichothecenes (T-2 toxin and deoxynivalenol) described in previous studies. Results confirm that at low concentration (25 ng mL⁻¹), OA is a potent myelotoxin for human hematopoietic progenitors, although platelets progenitors (CFU-MK) are most sensitive. DA did not exhibit any effect in the range of concentration tested. Taken together, these findings suggest that OA induced hematological abnormalities after chronic consumption similar to other food contaminants as trichothecenes.

Keywords:

• Myelotoxicity
• phycotoxins
• okadaic acid
• domoic acid
• human hematopoietic progenitors