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
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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