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| Tertiary Butylhydroquinone (TBHQ) Mitigates T-2 Toxin-induced Nephrotoxicity in Male Rats (Rattus norvegicus) via Anti-oxidative Stress and Anti-apoptotic Effects |
| CHEN Shu-Yan1,*, LI Yuan1,*, LIU Yu-Qing1, CHEN Li-Yuan1, CHEN Qing-Hua1, TANG Sheng-Qiu1,2, CHEN Yun1,2,** |
1 College of Biology and Agriculture, Shaoguan University, Shaoguan 512005, China;
2 Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, Shaoguan 512005, China |
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Abstract T-2 toxin is a highly toxic Fusarium toxin commonly found in grains and feed. It can activate apoptosis pathways by inducing oxidative stress and mitochondrial dysfunction, and damage important organs. The kidney, as a key organ for toxin metabolism and excretion, is more vulnerable to attack. However, effective protective strategies against its nephrotoxicity are still limited. As a phenolic antioxidant, tertiary butylhydroquinone (TBHQ) can activate the Nrf2/HO-1 pathway and counteract oxidative stress and apoptosis. Therefore,this study aims to investigate the protective effect of TBHQ against T-2 toxin-induced nephrotoxicity in male rats and to explore its molecular mechanisms. 40 male SD rats (Rattus norvegicus) were divided into Control group, T-2 group (T-2 toxin only), TBHQ+T-2 group (TBHQ i.p. for 14 d, followed by T-2 gavage for 7 d), and M group (simultaneous TBHQ and T-2 for 7 d). End-point analysis included serum markers (SCR, Cys-C, β2-MG), renal oxidative stress (SOD, CAT, GSH-PX, TAC, MDA), antioxidant gene expression (Sod,Cat,Gpx), histopathology (HE, Masson, PAS staining), and the cell apoptosis rate (TUNEL). The results showed that compared with Control group, serum levels of SCR and Cys-C were significantly elevated in rats of the T-2 group (P<0.05); renal SOD and MDA contents as well as the renal cell apoptosis rate were significantly increased (P<0.05), accompanied by damage to renal structure. However, TBHQ pretreatment significantly reversed these pathological changes: It reduced serum renal markers and MDA content (P<0.05), markedly reduced cell apoptosis (P<0.01), significantly improved histopathological lesions, and upregulated the mRNA expression of antioxidant genes Gpx (P<0.05) compared with the T-2 group. Furthermore, the protective effect of the TBHQ pretreatment regimen was superior to the M group. In conclusion, TBHQ mitigated T-2 toxin-induced renal injury in male rats by enhancing its anti-oxidative stress and anti-apoptotic effects, with pretreatment offering a more effective strategy. This study provides experimental evidence for elucidating the oxidative stress apoptosis mechanism of T-2 toxin nephrotoxicity as well as theoretical references for preventive protective measures against feed mycotoxin related kidney injury.
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Received: 03 October 2025
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Corresponding Authors:
** luxixiworld@163.com
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| About author:: * These authors contributed equally to this work |
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[1] 陈云, 陈丽圆, 宋文静, 等. 2025. T-2毒素对雄性动物生殖系统毒害机制的研究进展[J]. 畜牧兽医学报, 56(05): 2038-2046.
(Chen Y, Chen L Y, Song W J, et al.2025. Research progress on the mechanism of T-2 toxin's impact on male animal reproduction[J]. Acta Veterinaria et Zootechnica Sinica, 56(05): 2038-2046.)
[2] 吕道远, 俞娅芬, 储腊萍, 等. 2024. tBHQ对膜性肾病大鼠肾组织损伤、氧化应激抑制及肾皮质和细胞核Nrf2/NF-κB信号通路调控作用[J]. 山东医药, 64(27): 21-25.
(Lv D Y, Yu Y F, Chu L P, et al.2024. Inhibitory effects of tBHQ on renal injury and oxidative stress and its regulatory effect on Nrf2/NF-κB signaling pathway in renal cortex and nucleus of rats with membranous nephropathy[J]. Shandong Medical Journal, 64(27): 21-25.)
[3] 叶永丽, 高露, 纪剑, 等. 2024. 基于转录组学分析T-2毒素诱导细胞凋亡作用机制[J]. 食品与生物技术学报, 43(07): 56-66.
(Ye Y L, Gao L, Ji J, et al.2024. Mechanism of T-2 toxin induction in promoting cell apoptosis based on transcriptomics[J]. Journal of Food and Biotechnology, 43(07): 56-66.)
[4] 赵伟, 厉学武, Lamesgen DESSALEGN, 等. 2024. 我国饲料原料和配合饲料中T-2毒素、赭曲霉毒素A和伏马毒素的污染研究[J]. 动物营养学报, 36(04): 2690-2698.
(Zhao W, Li X W, Lamesgen DESSALEGN, et al.2024. A study of contamination of T-2 toxin, ochratoxin A and fumonisin in feed ingredients and compound feed in China[J]. Chinese Journal of Animal Nutrition, 36(04): 2690-2698.)
[5] Chen Y, Li B, Li K, et al.2024a. Superoxide dismutase nanozymes: Current status and future perspectives on brain disease treatment and diagnosis[J]. Chemical Communications (Cambrige England), 60(31): 4140-4147.
[6] An K, Shi B, Lv X, et al.2024. T-2 toxin triggers lipid metabolism disorder and oxidative stress in liver of ducks[J]. Ecotoxicology and Environmental Safety, 286: 117169.
[7] Chen Y, Zhang X, Lan S, et al.2024b. Tert-Butylhydroquinone mitigates T-2-Toxin-induced testicular dysfunction by targeting oxidative stress, inflammation, and apoptosis in rats[J]. Toxics, 12(5): 335.
[8] Deng S, Wu D, Li L, et al.2021. TBHQ attenuates ferroptosis against 5-fluorouracil-induced intestinal epithelial cell injury and intestinal mucositis via activation of Nrf2[J]. Cellular & Molecular Biology Letters, 26(1): 48.
[9] Hung Y, Hanson A, Urriola P, et al.2019. Addition of tert-butylhydroquinone (TBHQ) to maize oil reduces lipid oxidation but does not prevent reductions in serum vitamin E in nursery pigs[J]. Journal of Animal Science and Biotechnology, 10: 51.
[10] Li X, Wang X, Liu S, et al.2021. Betulinic acid attenuates T-2 toxin-induced cytotoxicity in porcine kidney cells by blocking oxidative stress and endoplasmic reticulum stress[J]. Comparative Biochemistry Physiology Part C: Toxicol & Pharmacol, 249: 109124.
[11] Liu Y, Dong R, Yang Y, et al.2021. Protective effect of organic selenium on oxidative damage and inflammatory reaction of rabbit kidney induced by T-2 toxin[J]. Biological Trace Element Research, 199(5): 1833-1842.
[12] Meneely J, Greer B, Kolawole O, et al.2023. T-2 and HT-2 toxins: Toxicity, occurrence and analysis: A review[J]. Toxins (Basel), 15(8): 481.
[13] Meng X, Zhang C, Guo Y, et al.2020. TBHQ attenuates neurotoxicity induced by methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT signaling pathways[J]. Oxidative Medicine and Cellular Longevity, 2020: 8787156.
[14] Wang Y, Liu P, Fan J, et al.2025. T-2 toxin nephrotoxicity: toxic effects, mechanisms, mitigations, and future perspectives[J]. Journal of Agriculture and Food Chemistry,73(5): 2732-2744.
[15] Xi M, Shen D, Dai P, et al.2022. TBHQ alleviates pyroptosis and necroptosis in chicken alveolar epithelial cells induced by fine particulate matter from broiler houses[J]. Poultry Science, 101(2): 101593.
[16] Yang D, He S, Tian X, et al.2026. Pinobanksin alleviates 4 ℃ semen preservation-induced oxidative damage and apoptosis in Wenchang Pig spermatozoa via the CaMKKβ/AMPK/Nrf2 pathway[J]. Veterinary Journal (London, England : 1997), 316: 106599.
[17] Zhang H, Li J, Xiang X, et al.2021. Tert-butylhydroquinone attenuates osteoarthritis by protecting chondrocytes and inhibiting macrophage polarization[J]. Bone &Joint research, 10(11): 704-713.
[18] Zhang X, Li B, Huo S, et al.2022. T-2 toxin induces kidney fibrosis via the mtROS-NLRP3-Wnt/beta-catenin axis[J]. Journal of Agriculture and Food Chemistry, 70(42): 13765-13777. |
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