Relevance of megalin receptor injury with nuclear factor-kappa B upregulation in acute kidney injury induced in rats.

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.

• Authors: Shereen Saeid Elshaer, Hend Mohamed Anwar
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 32 Issue 1 (Jan 2018) ISSN: 1099-0461 [Electronic] United States
• PMID: 29286200 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Biomarkers
• Low Density Lipoprotein Receptor-Related Protein-2
• NF-kappa B
• Tlr2 protein, rat
• Tlr4 protein, rat
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Malondialdehyde
• Glutathione
• Cadmium Chloride

Topics

• Acute Kidney Injury (etiology, metabolism, physiopathology)
• Animals
• Biomarkers (blood, metabolism)
• Cadmium Chloride (toxicity)
• Cadmium Poisoning (physiopathology)
• Gene Expression Regulation (drug effects)
• Glutathione (antagonists & inhibitors, chemistry, metabolism)
• Kidney (drug effects, metabolism, physiopathology)
• Lipid Peroxidation (drug effects)
• Low Density Lipoprotein Receptor-Related Protein-2 (antagonists & inhibitors, genetics, metabolism)
• Male
• Malondialdehyde (agonists, metabolism)
• NF-kappa B (agonists, genetics, metabolism)
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Random Allocation
• Rats, Sprague-Dawley
• Toll-Like Receptor 2 (agonists, genetics, metabolism)
• Toll-Like Receptor 4 (agonists, genetics, metabolism)