Effects Of Nivalenol Research Articles

Effects of nivalenol on hepatic drug-metabolizing activity in rats

Effects of nivalenol (NIV), a trichothecene mycotoxin, on hepatic drug-metabolizing activity and aflatoxin B 1 (AFB 1) metabolism were investigated in male rats. In rats fed the diets containing 6–12 ppm NIV for 2 or 4 wk, decreases in initial feed uptake, terminal weight gain and organ weights were evident. An increase in cytochrome P-450 activity was observed in the hepatic microsomes, and Western blot analysis revealed a transient increase in P4502B1/2, together with a slight induction of P4501A2. The activity of cytosolic glutathione S-transferase (GST) enzymes was also enhanced in the rats, and Western blot analysis demonstrated an elevation of GST 1–2. The formation of aflatoxin B 1-DNA adducts (AFB 1 DNA) was increased in experiments using hepatic microsomal preparations from rats fed the NIV diet, whereas supplementation with cytosol prepared from NIV-treated rats reduced the microsomal potential for adduct formation. In in vivo experiments, the AFB 1 DNA concentration in NIV-treated rats was lower than that in the controls. These results suggest that activities of cytochrome P − 450 and GST enzymes were increased in rats fed NIV for several weeks. Alteration of these phase 1 and phase 2 enzyme levels resulted in the modulation of AFB 1 adduction to DNA in vitro and in vivo.

Effects of nivalenol on pregnancy and fetal development of mice

Nivalenol (3,4,7,15-tetrahydroxy-12,13-epoxytrichothec-9-en-8-one) was injected intraperitoneally to pregnant mice at dose levels of 0, 0.1, 0.5 or 1.5 mg/kg b.w./day on days 7-15 of gestation. The highest dose caused stillbirths after vaginal hemorrhage in six of ten animals. High embryo lethality was recorded in the 2 highest dose groups (87.8 and 48.4%). No fetal malformations were observed in the test groups. A single administration of 3 mg/kg on day 7 affected the embryos within 10 hrs, damaged the placenta within 24 hrs, and revealed stillbirths at 48 hrs.