title: Modulatory effects of new curcumin analogues on gamma-irradiation - Induced nephrotoxicity in rats.
abstract: In the present study, a new series of 2-amino-pyran-3-carbonitrile derivatives of curcumin 2-7 have been synthesized via one-pot simple and efficient protocol, involving the reaction of curcumin 1 with substituted-benzylidene-malononitrile to modify the 1,3-diketone moiety. The structures of the synthesized compounds 2-7 were elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. The nephroprotective mechanism of these new curcumin analogues was evaluated on the post-gamma-irradiation (7 Gy) - induced nephrotoxicity in rats. Activation of Nrf2 by these curcumin analogues is responsible for the amendment of the antioxidant status, impairment of NF-κB signal, thus attenuate the nephrotoxicity induced post-γ-irradiation exposure. 4-Chloro-phenyl curcumin analogue 7 showed the most potent activity. In conclusion, the results of the present study demonstrate a promising role of these new curcumin analogues to attenuate the early symptoms of nephrotoxicity induced by γ-irradiation in rats via activation of Nrf2 gene expression. These new curcumin analogues need further toxicological investigations to assess their therapeutic index.
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box: 29, Nasr City, Cairo, Egypt. Electronic address: afmismail@gmail.com.
authors.forename: Amel F M
authors.initials: AF
authors.lastname: Ismail
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box: 29, Nasr City, Cairo, Egypt.
authors.forename: Nashwa H
authors.initials: NH
authors.lastname: Zaher
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box: 29, Nasr City, Cairo, Egypt.
authors.forename: Ebaa M
authors.initials: EM
authors.lastname: El-Hossary
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), P.O. Box: 29, Nasr City, Cairo, Egypt.
authors.forename: Marwa G
authors.initials: MG
authors.lastname: El-Gazzar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000150:complications / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D014131:Trace Elements / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D051267:NF-E2-Related Factor 2; D014131:Trace Elements; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D003474:Curcumin
keywords: Antioxidant; Curcumin analogues; Gamma-radiation; Nephrotoxicity; Nuclear Factor Erythroid-related Factor-2