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.
Murata
H
H
Department of Safety Research, National Institute of Animal Health, Tsukuba, Ibaraki 305-0856, Japan.
Sultana
P
P
Shimada
N
N
Yoshioka
M
M
D000818:Animals; D002417:Cattle; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D013329:Structure-Activity Relationship; D015025:Zearalenone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
D004968:Estrogens, Non-Steroidal; D015025:Zearalenone