Downregulation of HIF1-α, Smad-2, AKT, and Bax gene expression in sodium nitrite-induced lung injury via some antioxidants

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 NaNO₂ significantly 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.