Lycopene Protects Intestinal Epithelium from Deoxynivalenol-Induced Oxidative Damage via Regulating Keap1/Nrf2 Signaling

Abstract

Deoxynivalenol (DON) is a threatening mycotoxin primarily present in the agricultural environment, especially in food commodities and animal forages, and exerts significant global health hazards. Lycopene (LYC) is a potent antioxidant carotenoid mainly present in tomatoes and other fruits with enormous health benefits. The present study was designed to ascertain whether LYC could protect DON-induced intestinal epithelium oxidative injury by regulating Keap1/Nrf2 signaling in the intestine of mice. A total of forty-eight mice were randomly distributed into four groups (n = 12), Control (CON), 10 mg/kg BW LYC, 3 mg/kg BW DON, and 3 mg/kg DON + 10 mg/kg LYC BW (DON + LYC). The experimental groups were treated by intragastric administration for 11 days. Our results showed that LYC significantly increased average daily feed intake (ADFI), average daily gain (ADG), and repaired intestinal injury and barrier dysfunction, as evident by increased trans-epithelial electrical resistance (TEER) and decreased diamine oxidase (DAO) activity, as well as up-regulated tight junction proteins (occludin, claudin-1) under DON exposure. Furthermore, LYC treatment stabilized the functions of intestinal epithelial cells (Lgr5, PCNA, MUC2, LYZ, and Villin) under DON exposure. Additionally, LYC alleviated DON-induced oxidative stress by reducing ROS and MDA accumulation and enhancing the activity of antioxidant enzymes (CAT, T-SOD, T-AOC, and GSH-Px), which was linked with the activation of Nrf2 signaling and degradation of Keap1 expression. Conclusively, our findings demonstrated that LYC protects intestinal epithelium from oxidative injury by modulating the Keap1/Nrf2 signaling pathway under DON exposure. These novel findings could lead to future research into the therapeutic use of LYC to protect the DON-induced harmful effects in humans and/or animals.

Dietary Vitamin A Improved the Flesh Quality of Grass Carp (Ctenopharyngodon idella) in Relation to the Enhanced Antioxidant Capacity through Nrf2/Keap 1a Signaling Pathway

“…The higher expression of GSTr in muscle might lead to the more sensitive response to VA; however, this needs further characterization. In mammal, the expression of antioxidative enzymes genes (such as CAT and CuZnSOD ) can be modulated by Nrf2 signaling [ 43 ]. The present study observed that dietary VA deficiency decreased mRNA levels of Nrf2 , protein levels of total Nrf2, and nuclear Nrf2, while enhancing the mRNA levels of Keap1a in grass carp muscle.…”

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

“…38 However, LYC alleviated DON-induced oxidative stress by reducing ROS and MDA accumulation and enhancing the activity of antioxidant enzymes (SOD and GSH-Px) and T-AOC, which are linked to the activation of NRF2 signaling and a decline in KEAP1 expression. 39 Our results showed that co-exposure to ZEN, DON, and AFB1 caused oxidative damage (reduced T-AOC level and increased MDA and ROS contents) in the jejunum of mice. The protective effects of LYC against ZEN + DON + AFB1-induced oxidative damage have been demonstrated in this study.…”

Crucial Function of Caveolin-1 in Deoxynivalenol-Induced Enterotoxicity by Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis

“…Furthermore, the depth of the crypts in the small intestine of the mice was increased. Studies have shown that DON exposure caused oxidative stress in the intestine, including changes in the mRNA expressions of CAT, GSH-PX, and the serum MDA content, which led to a cascade of intestinal damage. , HO-1 is a well-known antioxidant factor, and several studies have shown that HO-1 plays an anti-inflammatory and antioxidant role, protecting the body from external damage. − In the present study, the protein and mRNA levels of HO-1 were found to decrease significantly in the DON-exposed group, which is consistent with previous studies. , Likewise, DON exposure reduced the mRNA levels of CAT and SOD-2 in mouse jejunum. In vitro, the results showed that 0.5–2 μM DON significantly reduced the protein and mRNA expressions of HO-1 and increased ROS generation.…”

“…29−31 In the present study, the protein and mRNA levels of HO-1 were found to decrease significantly in the DON-exposed group, which is consistent with previous studies. 11,32 Likewise, DON exposure reduced the mRNA levels of CAT and SOD-2 in mouse jejunum. In vitro, the results showed that 0.5−2 μM DON significantly reduced the protein and mRNA expressions of HO-1 and increased ROS generation.…”