Structure-activity relationships among zearalenone and its derivatives based on bovine neutrophil chemiluminescence

We compared the effects of zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, and its derivatives--a- and b-zearalenols (Zel), zearalanone (ZAN), and a- and b-zearalanols (Zal)--on bovine neutrophils in vitro by using chemiluminescence, a bactericidal parameter. ZEN, a-Zel, and b-Zel suppressed luminol-dependent, phorbol 12-myristate 13-acetate-elicited chemiluminescence at a concentration of 10(-5) M, whereas ZAN, a-Zal and b-Zal did not. The suppressive zearalenols are derived from ZEN through reduction of the C6'-ketone into hydroxide, whereas the non-suppressive ZAN and Zal group possesses a hydrogenated C1'-2' bond in place of the double bond adopted in the macrolide ring or ZEN and the zearalenols. In consideration of these structure-activity relationships among ZEN and its derivatives, we conclude that possession of the C1'-2' double bond is essential for zearalenones to induce neutrophil suppression.