title: Downregulation of HIF1-α, Smad-2, AKT, and Bax gene expression in sodium nitrite-induced lung injury via some antioxidants.
abstract: The aim of the current study is to evaluate the efficacy of pretreatment with either l-arginine (L-arg) or Carnosine (Car) and their combination in ameliorating some of the biochemical indices induced in the lung of sodium nitrite (NaNO2)-intoxicated rats. The results revealed that NaNO2significantly increased serum tumor necrosis factor-α, C-reactive protein, heat shock proteins-70, vascular endothelial growth factor, and Interleukin 6. Moreover, transforming growth factor-β, hypoxia-inducible factor, Smad-2, Protein Kinase B (AKT), and Bax were overexpressed, whereas Bcl2 protein was downregulated compared with the normoxic group. The administration of the fore mentioned antioxidants, either alone or in combination, markedly downregulated the previously mentioned inflammatory, apoptotic, as well as the fibrotic markers in lung tissue compared with the NaNO2-intoxicated rats. The histopathological examination reinforced the previous results. In conclusion, the current data revealed the efficacy of l-arg and Car in ameliorating the pulmonary damage via suppression of the inflammatory markers in response to NaNO2-intoxication. Interestingly the combination regimen showed the most significant effect.
authors.affiliation: Department of Therapeutic Chemistry, National Research Center, Giza, Egypt.
authors.forename: Mai O
authors.initials: MO
authors.lastname: Kadry
authors.affiliation: Department of Genetics and Cytology, National Research Center, Dokki, Egypt.
authors.forename: Hanaa Mahmoud
authors.initials: HM
authors.lastname: Ali
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D051899:Smad2 Protein / Q000096:biosynthesis*; D012977:Sodium Nitrite / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051028:bcl-2-Associated X Protein; D002336:Carnosine; D001120:Arginine; D051057:Proto-Oncogene Proteins c-akt; D012977:Sodium Nitrite
keywords: AKT; Bax; HIF1-α; Smad-2; carnosine; hypoxia; l-arginine; sodium nitrite