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

SCOPE: 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. METHODS AND RESULTS: Eighty 6-week-old male ICR mice are divided into four groups: CON group (solvent control), LYC group (10 mg kg-1 LYC), Co-M group (10 mg kg-1 ZEN + 1 mg kg-1 DON + 0.5 mg kg-1 AFB1), and LYC+Co-M group (10 mg kg-1 LYC + 10 mg kg-1 ZEN + 1 mg kg-1 DON + 0.5 mg kg-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. CONCLUSION: LYC successfully attenuates early hepatic fibrosis mainly through antioxidant activities and prevented mitochondrial injury.

Lycopene alleviates multiple-mycotoxin-induced toxicity by inhibiting mitochondrial damage and ferroptosis in the mouse jejunum.

Multiple mycotoxins contamination in foods and feeds threatens human and animal health after they accumulate in the food chain, producing various toxic effects. The common mycotoxins contaimination in feeds are zearalenone (ZEN), deoxynivalenol (DON), and aflatoxin B1 (AFB1), but the effects of their co-exposure on the jejunum are not well understood. Lycopene (LYC) has been reported to have antioxidant activity that alleviates jejunal damage. In this study, we investigated the possible role of LYC as a treatment to mitigate the combined effects of ZEN, DON, and AFB1 on the jejunum of mice. Eighty male specific-pathogen-free ICR mice were randomly allocated to treatments with LYC (10 mg kg-1) and/or ZEN + DON + AFB1 (10 mg kg-1 ZEN, 1 mg kg-1 DON, and 0.5 mg kg-1 AFB1). The results indicated that LYC alleviated ZEN + DON + AFB1-induced jejunal injury by ameliorating the jejunal structural injury and increasing the villus height/crypt depth ratio and the levels of tight junction proteins (zonula occludens 1 [ZO1], occludin1 and claudin1) in the mouse jejunum. LYC also inhibited the oxidative stress induced by co-exposure to ZEN, DON, and AFB1 via reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and enhancing the total antioxidant capacity (T-AOC). LYC also alleviated jejunal mitochondrial damage in the ZEN + DON + AFB1-affected mice, evident as an increase in mitochondrial fission 1 (Fis1) transcription and a reduction in mitochondrial mitofusin 1 (Mfn1) and Mfn2 transcription. Co-exposure to ZEN, DON, and AFB1 also significantly increased the transcription of ferroptosis-related genes (transferrin receptor 1 (Tfr1), ferritin heavy chain 1 [Fth1], solute carrier family 3 member 2 [Slc3a2], and glutathione peroxidase 4 [Gpx4]), TFR1 and Fe2+ concentration. Notably, LYC potentially alleviated ZEN + DON + AFB1-induced jejunal ferroptosis. These results demonstrate that LYC alleviates ZEN + DON + AFB1-induced jejunal toxicity by inhibiting oxidative stress-mediated ferroptosis and mitochondrial damage in mice.