Al-Zahrani Maryam H, Balgoon Maha J, El-Sawi Nagwa M, Alshubaily Fawzia A, Jambi Ebtihaj J, Khojah Sohair M, Baljoon Raghad S, Alkhattabi Nuha A, Baz Lina A, Alharbi Asmaa A, Ahmed Amira M, Abo Elkhair Ayat M, Ismael Mohamed, Gebril Sahar M
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Chemistry, Faculty of Science, Sohag University, Sohag, Egypt.
Front Mol Biosci. 2023 May 4;10:1172403. doi: 10.3389/fmolb.2023.1172403. eCollection 2023.
Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity. Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done. Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin's therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin's higher binding affinity than taurine. Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.
食源性单端孢霉烯族毒素T-2毒素是污染动物和人类食物的镰刀菌属产生的一种剧毒代谢产物，可导致多器官衰竭和健康危害。T-2毒素通过氧化应激诱导肝毒性，导致肝细胞毒性和基因毒性。在本研究中，对姜黄素和牛磺酸作为抗氧化剂对抗T-2诱导的肝毒性进行了研究和比较。给Wistar大鼠口服亚致死剂量（0.1mg/kg）的T-2毒素，持续2个月，随后给予姜黄素（80mg/kg）和牛磺酸（50mg/kg），持续3周。对肝酶、血脂谱、硫代巴比妥酸反应性物质（TBARs）、α-L-岩藻糖苷酶（AFU）、肿瘤坏死因子-α（TNF-α）、总谷胱甘肽进行生化评估，进行分子对接、组织学和免疫组化检测抗转化生长因子-β1（TGFβ1）、双链DNA损伤（H2AX）、再生（KI67）和凋亡（活化半胱天冬酶3）标记物。与T-2毒素相比，姜黄素和牛磺酸治疗显著改善了肝毒性，血红蛋白、血细胞比容和谷胱甘肽、肝糖原以及KI-67免疫反应性肝细胞显著增加。尽管肝酶、炎症、纤维化、TGFβ1免疫表达以及H2AX和活化半胱天冬酶3阳性肝细胞显著减少。值得注意的是，通过组织形态计量学参数，姜黄素的治疗效果优于牛磺酸。此外，姜黄素和牛磺酸对DNA序列结构影响的分子对接显示，姜黄素的结合亲和力高于牛磺酸。姜黄素和牛磺酸均作为强抗氧化剂改善了T-2诱导的肝毒性，姜黄素的效果更佳。
