Fumonisin B 1 ( FB 1 ) is a common mycotoxin contamination in agricultural commodities being considered as a significant risk to human and livestock health, while the mechanism of FB 1 immunotoxicity are less understood, especially in chicken. Given that extracellular traps as a novel defense mechanism of leukocytes play an important role against foreign matters, in this study we aimed to investigate the effects of FB 1 on chicken heterophil extracellular traps ( HETs ) formation. Our result showed that FB 1 induced HETs release in chicken heterophils observed via immunostaining, and it was concentration-dependent during 10 to 40 μM. Moreover, in 40 μM FB 1 -exposed chicken heterophils, reactive oxygen species ( ROS ) level was increased, while catalase ( CAT ), superoxide dismutase ( SOD ), and glutathione peroxidase ( GSH-Px ) activity and glutathione ( GSH ) content were decreased. Simultaneously, FB 1 (40 μM) activated ERK and p38 MAPK signaling pathways via increasing the phosphorylation level of ERK and p38 proteins. However, pretreatment of SB202190, U0126, and diphenyleneiodonium chloride ( DPI ) did not change FB 1 -triggered ROS production and HETs formation, suggesting FB 1 -induced HETs was a nicotinamide adenine dinucleotide phosphate ( NADPH ) oxidase, p38, and extracellular regulated protein kinases ( ERK ) signaling pathways-independent process. Inhibition of peptidyl arginine deiminase 4 ( PAD4 ) enzyme and P2 × 1 receptor showed their vital role in 40 μM FB 1 -triggered HETs. This study reported for the first time that 40 μM FB 1 induced the release of HETs in heterophils, and it was related to ROS production, PAD4, and P2 × 1, but was independent of NADPH oxidase, p38 and ERK signaling pathways, which might provide a whole novel perspective of perceiving and understanding the role of FB 1 in immunotoxicity.

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Deoxynivalenol (DON), one of the most prevalent mycotoxins found in food and feed, can cause gastrointestinal inflammation and systemic immunosuppression, presenting a serious hazard to human and animal health. Quercetin (QUE) is a plant polyphenol with anti-inflammatory and antioxidant properties. In this research, we investigated the potential function of QUE as a treatment for DON-induced intestinal damage. Thirty male specific-pathogen-free BALB/c mice were randomly allocated to treatment with QUE (50 mg/kg) and/or DON (0, 0.5, 1, and 2 mg/kg). We found that QUE attenuated DON-induced intestinal damage in mice by improving jejunal structural injury and changing tight junction proteins (claudin-1, claudin-3, ZO-1, and occludin) levels. QUE also suppressed DON-triggered intestinal inflammation by inhibiting the TLR4/NF-κB signaling pathway. Meanwhile, QUE decreased the oxidative stress caused by DON by enhancing the concentrations of SOD and GSH, while diminishing the contents of MDA. In particular, QUE reduced DON-induced intestinal ferroptosis. DON-induced intestinal damage elevated TfR and 4HNE levels, along with transcription levels of ferroptosis-related genes (PTGS2, ACSL4, and HAMP1) while diminishing mRNA levels of FTH1, SLC7A11, GPX4, FPN1, and FSP1, all of which were reversed by QUE treatment. Our findings imply that QUE alleviates DON-induced intestinal injury in mice by inhibiting the TLR4/NF-κB signaling pathway and ferroptosis. In this study, we elucidate the toxicological mechanism of DON, provide a basic foundation or theory for future DON prevention and treatment, and explore strategies to prevent and alleviate DON's hazardous effects.

This study aimed to investigate the protective effects and mechanisms of myricetin on acute liver failure in mice induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal). Our results showed myricetin (25, 50 and 100 mg/kg) pretreatment significantly improved the pathological changes of liver tissues, decreased serum ALT and AST (p < 0.001) induced by LPS/D-GalN. Moreover, MDA and MPO levels were reduced (p < 0.001), CAT and SOD activities were increased (p < 0.001) with myricetin (50 and 100 mg/kg) pretreatment. Likewise, inflammatory cytokines TNF-α and IL-6 mRNA in liver tissues were markedly decreased (p < 0.001) by myricetin.Besides, Nrf2 protein expression was drastically elevated (p < 0.001) by myricetin (25, 50 and 100 mg/kg). All these findings imply that myricetin may protect against acute liver failure by suppressing inflammation and regulating oxidative stress via Nrf2 signaling, and that it may be a possible strategy to avoid liver damage.