Journal Article

The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice

Puri, Sanjeev, Singla, Surinder K., Kumar, Dev, Puri, Veena

2015

Overview

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / Acids / Acute kidney failure / Acute Kidney Injury - chemically induced / Acute Kidney Injury - genetics / Acute Kidney Injury - metabolism / Ammonium / Animals / Antioxidants - pharmacology / Apoptosis / Biochemistry / Biology and Life Sciences / Cell cycle / Cellular structure / Creatinine / Deregulation / Folic Acid / Gangrene / Gene Expression / Genetic aspects / Health aspects / Health risks / Immunohistochemistry / Immunology / Inflammation / Injuries / Kidney - drug effects / Kidney - metabolism / Kidney - pathology / Kidney Cortex - metabolism / Kidney Cortex - pathology / Kidney Cortex - ultrastructure / Kidney Function Tests / Kidneys / Lymphocytes B / Male / Medicine and Health Sciences / Mice, Inbred BALB C / Microscopy, Electron, Transmission / Mitochondria / Morbidity / Mortality / Necrosis / NF-kappa B - antagonists & inhibitors / NF-kappa B - genetics / NF-kappa B - metabolism / NF-kappa B p52 Subunit - antagonists & inhibitors / NF-kappa B p52 Subunit - genetics / NF-kappa B p52 Subunit - metabolism / NF-κB protein / p53 Protein / Proteins / Pyrrolidine / Pyrrolidines - pharmacology / RelA protein / Renal function / Research and Analysis Methods / Reverse Transcriptase Polymerase Chain Reaction / Risk factors / Rodents / Senescence / Thiocarbamates - pharmacology / Transcription Factor RelA - antagonists & inhibitors / Transcription Factor RelA - genetics / Transcription Factor RelA - metabolism / Transcription factors / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - metabolism / Urea