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<p>Schistosomiasis drastically affects human health, where <i>S. mansoni</i>-induced hepatic fibrosis remains a serious problem with no available drug yet. The current study aimed to evaluate the hepatoprotective effects of Vildagliptin (Vilda), Diaminodiphenyl Sulfone (DDS), and their combination (Vilda/DDS) against <i>S. mansoni</i>-induced hepatic fibrosis and elucidate their underlying molecular mechanisms. <i>S.mansoni</i>-infected mice were administered praziquantel (PZQ) for two consecutive days, or Vilda, DDS, and Vilda/DDS for 14 consecutive days. Schistosomiasis-induced hepatic fibrosis was assessed parasitologically, biochemically, and pathologically. Results revealed that Vilda, DDS, and Vida/DDS treatments significantly reduced worm count, oogram stages, ova count, and ameliorated the granulomatous inflammatory reactions and hepatotoxicity indices. Moreover, they enhanced hepatic Nrf2/HO-1 pathway with significant increasing SOD and reducing MDA levels. Furthermore, they significantly downregulated the hepatic TLR4/NF-κB and NLRP3 inflammasome pathways leading to a significant reduction in TNF-α and caspase-1 levels which is important in the activation of IL-1β and caspase-3. Notably, significant downregulation in hepatic TGF-β1, α-SMA, and MMP-9 expressions were also recorded. In conclusion, Vilda/DDS showed antioxidant, anti-inflammatory and antifibrotic activities in comparison to either Vilda or DDS alone against <i>S. mansoni</i>-induced hepatic fibrosis. Therefore, Vilda/DDS is a promising approach for managing <i>S. mansoni</i> infection, liver fibrosis, and associated disease morbidity.</p>

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The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月24日

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  • Amira S. Hendawy,
  • Abdel-Nasser A. Sabra,
  • Mina Y. George,
  • Eman Rashad,
  • Ebtehal El-Demerdash,
  • Sanaa S. Botros

摘要

Schistosomiasis drastically affects human health, where S. mansoni-induced hepatic fibrosis remains a serious problem with no available drug yet. The current study aimed to evaluate the hepatoprotective effects of Vildagliptin (Vilda), Diaminodiphenyl Sulfone (DDS), and their combination (Vilda/DDS) against S. mansoni-induced hepatic fibrosis and elucidate their underlying molecular mechanisms. S.mansoni-infected mice were administered praziquantel (PZQ) for two consecutive days, or Vilda, DDS, and Vilda/DDS for 14 consecutive days. Schistosomiasis-induced hepatic fibrosis was assessed parasitologically, biochemically, and pathologically. Results revealed that Vilda, DDS, and Vida/DDS treatments significantly reduced worm count, oogram stages, ova count, and ameliorated the granulomatous inflammatory reactions and hepatotoxicity indices. Moreover, they enhanced hepatic Nrf2/HO-1 pathway with significant increasing SOD and reducing MDA levels. Furthermore, they significantly downregulated the hepatic TLR4/NF-κB and NLRP3 inflammasome pathways leading to a significant reduction in TNF-α and caspase-1 levels which is important in the activation of IL-1β and caspase-3. Notably, significant downregulation in hepatic TGF-β1, α-SMA, and MMP-9 expressions were also recorded. In conclusion, Vilda/DDS showed antioxidant, anti-inflammatory and antifibrotic activities in comparison to either Vilda or DDS alone against S. mansoni-induced hepatic fibrosis. Therefore, Vilda/DDS is a promising approach for managing S. mansoni infection, liver fibrosis, and associated disease morbidity.