Hikmat Suhair, Hasan Aya, Hamadneh Lama, Alwahsh Mohammad, Al-Kouz Sameer, Al-Hiari Yusuf, Al-Jammal Basmah, Al-Qirim Tariq, Hussein Buthaina
Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, 11733, Jordan.
Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, 19117, Jordan.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 26. doi: 10.1007/s00210-025-04174-z.
Hyperlipidemia is a heterogeneous disorder that refers to increased lipid levels in the blood. The purpose of this study was to investigate the molecular effects of novel carboxamide derivatives on a hyperlipidemic male rat model induced by Triton WR-1339 in comparison to fenofibrate using liver, endothelial, and adipose tissue samples. Nitrofuran-2-carboxamide derivatives were compared to fenofibrate to evaluate their molecular hypolipidemic actions. The gene expression profiles of pathways related to triglycerides including PPAR-alpha and beta-oxidation pathways were evaluated in an acute hyperlipidemia rat model using RT-PCR followed by protein-protein interaction networks that were produced using the STRING database. The three novel compounds showed a significant effect on the lipid profile. Several genes were reported to be overexpressed by Triton WR-1339, including CPT1 A in liver tissue and APOE in adipose tissue. Most of the overexpressed genes were downregulated by carboxamide derivatives, with significant decreases in CPT1 A and APOE gene expression levels. On the other hand, several genes were reported to be downregulated by Triton WR-1339, including ACOX1 in liver tissue, LPL, ACADM and ACAA2 in endothelial tissue, and LPL and ACADM in adipose tissue. Most of the downregulated genes were significantly upregulated by carboxamide derivatives. In summary, the three novel compounds were found to improve hypertriglyceridemia with significant changes in gene expression of key enzymes in lipids metabolism, mainly LPL.
高脂血症是一种异质性疾病，指血液中脂质水平升高。本研究的目的是，与非诺贝特相比，使用肝脏、内皮和脂肪组织样本，研究新型羧酰胺衍生物对Triton WR - 1339诱导的高脂血症雄性大鼠模型的分子效应。将硝基呋喃 - 2 - 羧酰胺衍生物与非诺贝特进行比较，以评估它们的分子降血脂作用。在急性高脂血症大鼠模型中，使用逆转录 - 聚合酶链反应（RT - PCR）评估与甘油三酯相关途径（包括过氧化物酶体增殖物激活受体α（PPAR - alpha）和β - 氧化途径）的基因表达谱，随后使用STRING数据库生成蛋白质 - 蛋白质相互作用网络。这三种新型化合物对血脂谱有显著影响。据报道，Triton WR - 1339使几个基因过度表达，包括肝脏组织中的肉碱棕榈酰转移酶1A（CPT1 A）和脂肪组织中的载脂蛋白E（APOE）。大多数过度表达的基因被羧酰胺衍生物下调，CPT1 A和APOE基因表达水平显著降低。另一方面，据报道，Triton WR - 1339使几个基因下调，包括肝脏组织中的酰基辅酶A氧化酶1（ACOX1）、内皮组织中的脂蛋白脂肪酶（LPL）、酰基辅酶A脱氢酶中链（ACADM）和乙酰辅酶A酰基转移酶2（ACAA2），以及脂肪组织中的LPL和ACADM。大多数下调的基因被羧酰胺衍生物显著上调。总之，发现这三种新型化合物可改善高甘油三酯血症，脂质代谢关键酶的基因表达有显著变化，主要是LPL。
