Co-occurrence of Mycotoxin-Induced Hepatotoxicity in Mice Inhibited by Lycopene: Mitochondrial Impairment and Early Hepatic Fibrosis.

Abstract

Mycotoxins co-contamination of agricultural products poses a serious threat to human and animal health, especially hepatic dysfunction. Zearalenone (ZEN), deoxynivalenol (DON), and aflatoxin B1 (AFB1) are three commonly co-occurring mycotoxins. This study is to determine whether lycopene (LYC) can alleviate hepatic toxicity induced by the co-occurrence of ZEN, DON, and AFB1 in mice. Eighty 6-week-old male ICR mice are divided into four groups: CON group (solvent control), LYC group (10 mgkg-1 LYC), Co-M group (10 mgkg-1 ZEN + 1 mgkg-1 DON + 0.5 mgkg-1 AFB1), and LYC+Co-M group (10 mgkg-1 LYC + 10 mgkg-1 ZEN + 1 mgkg-1 DON + 0.5 mgkg-1 AFB1). The results show that LYC can suppress the co-occurrence of mycotoxin-induced mitochondrial swelling and vacuolization accompanied by dysregulation of indices of mitochondrial dynamics (Mitofusin 1 (Mfn1), Mfn2, Optic atrophy 1 (Opa1), Dynamin-related protein 1 (Drp1), Fission 1 (Fis1) at the mRNA level; DRP1 and FIS1 at the protein level). LYC effectively inhibits co-occurrence of mycotoxin-induced activation of Cytochrome P450 2E1, and early fibrosis, as determined by staining with Masson's trichrome and α-SMA protein. LYC successfully attenuates early hepatic fibrosis mainly through antioxidant activities and prevented mitochondrial injury.