Quercetin Alleviates Deoxynivalenol-Induced Intestinal Damage by Suppressing Inflammation and Ferroptosis in Mice

Abstract

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.

Ferritinophagy Is Critical for Deoxynivalenol-Induced Liver Injury in Mice

“…Transmission electron microscopy (TEM) revealed structurally incomplete mitochondria with deficient cristae in cells from the DON-treated groups (Figure G,H and Table S5). Oxidative stress constitutes a significant aspect of cellular damage induced by DON . In the groups treated with DON, there was an elevation in H 2 O 2 levels, accompanied by a reduction in the levels of CAT, T-AOC, and T-SOD (Figure I–L).…”

“…The oral median lethal dosage of DON was 46 mg/kg. The dose of DON used was based on the recent report, at doses of 150 μg/kg (1/300 LD50) and 2300 μg/kg (1/20 LD50). Mice (eight per group) were separated into three groups as follows: Con (control), DON150 (150 μg/kg b.w.…”

Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis—A Systematic Review

“…Numerous studies have substantiated their positive impact on human health, underscoring their potent antioxidant, anti-inflammatory, and anticancer properties. Consequently, it is unsurprising that researchers have shown considerable interest in these compounds, as they demonstrate substantial potential in inhibiting ferroptosis [ 95 , 118 , 197 , 306 ].…”

Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway

“…On the other hand, ferroptosis, a unique form of non-apoptotic cell death, can be initiated by the accumulation of iron and production of reactive oxygen species (ROS) from lipid peroxidation 31 . Several studies have identified ferroptosis as an important contributor to the occurrence and progression of various diseases and inhibiting ferroptosis may lessen inflammatory response and intestinal epithelial cells (IECs) injury in IBD 32 - 34 . However, it remains unclear whether the intestinal cGAS-STING pathway is involved in IEC ferroptosis during colitis and how SP/NK1R signaling affects it in maintaining epithelial homeostasis.…”