Effects of nivalenol on hepatic drug-metabolizing activity in rats

Abstract

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.