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N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide decreases triglyceride levels by downregulation of Apoc3 gene expression in acute hyperlipidemic rat model.

Abstract
Hyperlipidemia is a known cause of coronary vascular diseases, which is a major cause of death in many parts of the world. Targeting several pathways that lead to increase in lipid profiles is of great potential to control diseases. 1H-indole-2-carboxamide derivatives were tested for their hypolipidemic activity at the molecular level in comparison with bezafibrate. The gene expression profiles of lipoprotein signaling and cholesterol metabolism and fatty acid metabolism PCR arrays were determined in rats with acute hyperlipidemia induced by Triton WR1339. Lipid profiles of serum from treated rats showed significant hypolipidemic effect by the compounds. Several genes of potential interest were reported to be overexpressed by Triton WR1339 including Apoc3, Apob, Hmgcs2, Apoa1, Apoe, Apof, acsl1, and Decr1. Most of the overexpressed genes were downregulated by N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide with significant decreases in Apoc3, Apob, Acaa2, Acsl1, and Slc247a5 gene expression levels. N-(4-Benzoylphenyl)-1H-Indole-2-Carboxamide and bezafibrate did not significantly affect the gene expression levels which were increased with acute hyperlipidemia induced by Triton WR1339. In conclusion, gene expression profiling identified the possible mechanism in which Triton WR1339 induces its acute hyperlipidemic effect which was reversed by the use of N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide.
AuthorsLama Hamadneh, Luay Al-Essa, Suhair Hikmat, Tariq Al-Qirim, Ghassan Abu Sheikha, Yusuf Al-Hiari, Nisrin Azmy, Ghassan Shattat
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 431 Issue 1-2 Pg. 133-138 (Jul 2017) ISSN: 1573-4919 [Electronic] Netherlands
PMID28255847 (Publication Type: Journal Article)
Chemical References
  • Apolipoprotein C-III
  • Imidazoles
  • Triglycerides
  • Polyethylene Glycols
  • tyloxapol
Topics
  • Animals
  • Apolipoprotein C-III (biosynthesis)
  • Disease Models, Animal
  • Down-Regulation (drug effects)
  • Hyperlipidemias (blood, chemically induced, drug therapy)
  • Imidazoles (pharmacology)
  • Male
  • Polyethylene Glycols (toxicity)
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides (blood)

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