ArticleCellular & molecular biology letters2021
TBHQ attenuates ferroptosis against 5-fluorouracil-induced intestinal epithelial cell injury and intestinal mucositis via activation of Nrf2.
Article in Cellular & molecular biology letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 93 citations in OpenAlex.
- Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026Review
- PARK7-Nrf2 axis mitigates NLRP3-driven inflammation to rescue neurovascular unit from hypoxia/reoxygenation-induced necroptosis.Journal of translational medicine · 2026Article
- Food preservative tBHQ modulates Th17/TCurrent research in toxicology · 2026Article
- HNRNPC reprograms cancer metabolism to drive acquired chemoresistance in colorectal cancer by repressing of Nrf2/SLC7A11-dependent ferroptosis.Cell communication and signaling : CCS · 2025Article
- 6-gingerol alleviates chemotherapy-induced nausea and vomiting by inhibiting ferroptosis via the regulation of iron homeostasis.Cancer chemotherapy and pharmacology · 2025Article
- Pediococcus pentosaceus PP34 Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis via Inhibiting Oxidative Stress and Restoring the Gut Microbiota.Probiotics and antimicrobial proteins · 2025Article
- The emerging role of ferroptosis in the pathological development and progression of sepsis.Military Medical Research · 2025Review
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.Acta pharmaceutica Sinica. B · 2025Review
- Tertiary butylhydroquinone regulates oxidative stress in spleen injury induced by gas explosion via the Nrf2/HO-1 signaling pathway.Scientific reports · 2025Article
- Intravenous immunoglobulin ameliorates doxorubicin-induced intestinal mucositis by inhibiting the Syk/PI3K/Akt axis and ferroptosis.Apoptosis : an international journal on programmed cell death · 2025Article
- Exploring the Mechanisms of the Antioxidants BHA, BHT, and TBHQ in Hepatotoxicity, Nephrotoxicity, and Neurotoxicity from the Perspective of Network Toxicology.Foods (Basel, Switzerland) · 2025Article
- Restore intestinal steady-state: new advances in the clinical management of chemotherapy-associated diarrhea and constipation.Journal of molecular histology · 2025Review
- Camellia Tea Saponin Ameliorates 5-Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation.Nutrients · 2025Article
- Farrerol inhibits ferroptosis and protects against LPS-induced acute lung injury by targeting the RUNX1/SLC7A11 axis.Frontiers in immunology · 2025Article
- Ferroptosis: a double-edged sword that enhances radiation sensitivity and facilitates radiation-induced injury in tumors.Frontiers in immunology · 2025Review
- Bletilla oligosaccharides improved 5-fluorouracil-induced intestinal mucositis in mice by activating NF-κB signalling pathway and regulating intestinal microbiota.Frontiers in pharmacology · 2025Article
- The USP11/Nrf2 positive feedback loop promotes colorectal cancer progression by inhibiting mitochondrial apoptosis.Cell death & disease · 2024Article
- Iota-Carrageenan from Marine AlgaBiomedicines · 2024Article
- FGFR2-triggered autophagy and activation of Nrf-2 reduce breast cancer cell response to anti-ER drugs.Cellular & molecular biology letters · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIntestinal mucositis is a common side effect of chemotherapy and radiotherapy. Very few drugs can efficiently ameliorate it. Tertiary butylhydroquinone (TBHQ) is a widely used food preservative with known immunomodulatory activity. Whether it has an effect on intestinal mucositis remains unknown. In this study, we investigated the role and mechanism of action of TBHQ on 5-fluorouracil-induced (5-FU-induced) human intestinal epithelial cell (HIEC) injury and intestinal mucositis in mice.
methodsWe established a cell model of HIEC injury and a mouse model of intestinal mucositis via treatment with 5-FU. Cell death, Cell Counting Kit-8, and lactate dehydrogenase (LDH) release were assessed for the HIECs. Diarrhea, body weight, intestinal length, mucosal damage, and the levels of IL-6, TNF-α, IL-1β, glutathione, reactive oxygen species, and malondialdehyde were determined for the mice. Additionally, we performed immunohistochemical analysis, immunofluorescence, western blotting, quantitative real-time PCR, and ELISA to examine the effects of TBHQ. Finally, HIECs were transfected with an Nrf2 gene silencer to verify its role in ferroptosis. All data were analyzed using one-way analysis of variance or paired t-tests.
resultsTBHQ markedly decreased LDH release and cell death and improved the proliferative ability of 5-FU-treated HIECs. The TBHQ-treated mice showed reduced weight loss, a lower diarrhea score, and longer colons than the 5-FU-treated mice. The in vivo expressions of IL-1β, IL-6, and TNF-α were suppressed by TBHQ treatment. Ferroptosis was shown to be involved in 5-FU-induced intestinal mucositis, and TBHQ markedly hampered its activation. Mechanistically, TBHQ activated Nrf2 effectively and selective Nrf2 knockdown significantly reduced the anti-ferroptotic functions of TBHQ in 5-FU-treated HIECs.
conclusionsTBHQ attenuates ferroptosis in 5-FU-induced intestinal mucositis, making it a potential novel protective agent against intestinal mucositis.
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