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Abstract: Proximal tubule protein take‐up is interceded by 2 receptors, megalin and cubilin. These receptors rescue an assortment of filtered ligands including fundamental vitamins and hormones. The objective of this study was to investigate the potential relation of megalin receptor injury with nuclear factor‐kappa B (NF‐κB) upregulation in acute kidney injury rat model. Twenty four rats were allocated into two groups: control group received saline, while the second group was intoxicated with cadmium chloride (2.4 mg Cd/kg/day i.p) for 30 days. Blood urea nitrogen, serum creatinine, tissue oxidant–antioxidant parameters (malondialdehyde [MDA] and reduced glutathione [GSH]) and expression levels for NF‐κB, toll like receptor‐2 (TLR2), toll like receptor‐4 (TLR4), and megalin receptor were estimated. Noticeable downregulation of megalin receptor versus upregulation of NF‐κB, TLR2, and TLR4 were observed in AKI rat model together with significant elevation in MDA as well as significant reduction in GSH. The study concluded that the oxidative stress in kidney tissue leads to megalin receptor damage, which indeed motivates upregulation of NF‐κB through TLRs 2 and 4 pathways. [ABSTRACT FROM AUTHOR]

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