Protective impact of against γ-irradiation and thioacetamide-induced nephrotoxicity in rats mediated by regulation of micro-RNA 1 and micro-RNA 146a.

Chronic kidney disease develops popular and medical health problems, especially in developing countries. The objective of this study is to investigate the protective mechanism of against γ-irradiation (R) and/or thioacetamide (TAA)-induced nephrotoxicity in rats. Rats intoxicated with R or TAA showed alterations in kidney function markers (urea, creatinine, albumin, and total protein contents), oxidative stress markers (malondialdehyde, reduced glutathione), antioxidant enzymes (superoxide dismutase, catalase), and several inflammatory markers (including, the high-sensitivity C-reactive protein, hypoxia-inducible factor-1 alpha, tumor necrosis factor-alpha, interferon-gamma, some interleukins, and nuclear factor-kappa B). Rats also acquired apoptosis, evinced by high caspase-3 efficacy. This nephrotoxicity mediated by upregulation of the messenger RNA (mRNA) gene expression of the autophagy markers: Beclin-1, microtubule-associated protein LC3, p62 binding protein, immunoglobulin G receptor Fcγ receptor (FcγR), micro-RNA-1 (miR-1), protein expression of phospho-adenosine monophosphate-activated protein kinase, and phospho-mammalian target of rapamycin, along with downregulation of miR-146a mRNA gene expression and alteration of calcium and iron levels. The combined treatment R/TAA enhanced the observed oxidative stress, inflammation, apoptosis, and autophagy that mediated by higher upregulation of miR-1 and downregulation of miR-146a mRNA gene expression. administration exhibited a nephroprotective impact on R, TAA, and R/TAA toxicities via regulating miR-1 and miR-146a mRNA gene expression that monitored adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling.