Toxicokinetics and tissue depletion of Fusarenon-X and its metabolite nivalenol in piglets

Abstract

Fusarenon-X (FX) is one of the trichothecene mycotoxins mainly produced by Fusarium crookwellense, which naturally occurs in agricultural commodities such as wheat and barley. To investigate the toxicokinetics of FX and its metabolite nivalenol (NIV), FX was then administered intravenously or orally to piglets at a dosage of 1mg/kg body weight. The concentrations of FX and NIV in the plasma and various tissues were measured using LC-MS/MS. The plasma concentrations of FX in the piglets were determined up to 24h and 48h after iv and po administration, respectively, and the concentration of NIV was detected up to 12h after both types of administration. The Cp0 of FX was 580.28±140.81ng/ml after iv administration. The values of t1/2β, Vss and Foral were 1.71±0.74h, 0.009±0.002ml and 74.40±18.96%, respectively. FX and NIV were detectable in the vital organs up to 24h after po administration. The peak level of FX in the liver, the kidney, and the spleen, respectively, were 165.95±9.68ng/g, 66.29±8.48 and 7.35±0.69ng/g at 3h following po administration. In vitro of liver postmitochondrial fractions with FX demonstrated that the liver and kidney are capable of FX-to-NIV metabolism.