Rashdan Huda R M, Hassan Sarah, Maher Sara, Okasha Hend
Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Buhouth St, Dokki, Giza, 12622, Egypt.
Electron Microscopy Department, Theodor Bilharz Research Institute, Giza, Egypt.
Sci Rep. 2025 May 20;15(1):17546. doi: 10.1038/s41598-025-02483-0.
Liver necrosis is the irreversible loss of hepatocytes through toxin-induced injury, ischemia, or infection to produce organ dysfunction. It is a significant pathological marker in many liver disorders, including cirrhosis, and hepatitis, and contributes to organ failure and general systemic effects. This research aims to evaluate the protective effects of a newly synthesized compound named 1-(5-((1-(1-(4-((4-(4-(1-((5-acetyl-3-phenyl-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)ethyl)-5-methyl-1H-1,2,3-triazol-1-yl)phenyl)sulfonyl)phenyl)-5-methyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-4-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one (TTTE) sulfone-bis chalcone derivative on liver necrosis caused by TAA therapy using murine model. The research investigates optimal cellular pathways which demonstrate the therapeutic properties of TTTE as a potential treatment for liver injuries. The newly prepared compound TTTE was successfully characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR) spectroscopy, carbon-13 nuclear magnetic resonance (13C-NMR), The safety of the as-prepared compound TTTE was determined based on weight changes and the behaviors in all the groups were monitored for 21 days. The effect of treatment of TTTE at different doses (300, 200, and 100 mg/kg B.W.) was studied. High-dose TTTE revealed a 62.5% survival rate compared to the untreated TAA group (40%). Molecular analysis exhibited that high-dose TTTE downregulated Cas-3, TIMP-1, and proinflammatory cytokines (TNF-α, NF-κB, and IL-6) compared to untreated TAA. Results of histopathological and IHC examinations exhibited high TTTE dose have no signs of liver injury with suppression in TGF-β expression as a result of anti-inflammatory response. Our study concluded that the synthesized compound, TTTE has a potential therapeutic strategy in mitigating liver necrosis.
肝坏死是指肝细胞通过毒素诱导的损伤、缺血或感染而发生不可逆性丧失，进而导致器官功能障碍。它是许多肝脏疾病（包括肝硬化和肝炎）中的一个重要病理标志，并会导致器官衰竭和全身影响。本研究旨在评估一种新合成的名为1-(5-((1-(1-(4-((4-(4-(1-((5-乙酰基-3-苯基-1,3,4-噻二唑-2(3H)-亚基)肼基)乙基)-5-甲基-1H-1,2,3-三唑-1-基)phenyl)sulfonyl)phenyl)-5-甲基-1H-1,2,3-三唑-4-基)乙叉基)肼基)-4-苯基-4,5-二氢-1,3,4-噻二唑-2-基)乙-1-酮（TTTE）的砜-双查尔酮衍生物对使用小鼠模型的TAA疗法引起的肝坏死的保护作用。该研究调查了最佳细胞途径，这些途径证明了TTTE作为肝损伤潜在治疗方法的治疗特性。新制备的化合物TTTE通过傅里叶变换红外光谱（FT-IR）、质子核磁共振（1H-NMR）光谱、碳-13核磁共振（13C-NMR）成功表征，基于体重变化确定了所制备化合物TTTE的安全性，并对所有组的行为进行了21天的监测。研究了不同剂量（300、200和100mg/kg体重）的TTTE治疗效果。与未治疗的TAA组（40%）相比，高剂量TTTE显示出62.5%的存活率。分子分析表明，与未治疗的TAA相比，高剂量TTTE下调了Cas-3、TIMP-1和促炎细胞因子（TNF-α、NF-κB和IL-6）。组织病理学和免疫组化检查结果显示，高剂量TTTE没有肝损伤迹象，由于抗炎反应，TGF-β表达受到抑制。我们的研究得出结论，合成化合物TTTE在减轻肝坏死方面具有潜在的治疗策略。
