Dysregulation of kidney structural polysaccharides and miRNA-21/SIRT1/NF-κB axis of injury and fibrosis in thioacetamide-induced nephrotoxicity is protected by resveratrol.
Mohammed Alshehri, Ibrahim Tawhari, Faris Almasabi, Hind Zafrah, Alia Albawardi, Nervana M Bayoumy, Mohamed Abd Ellatif, Bahjat Al-Ani, Norah M Alzamil, Samaa S Kamar
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引用次数: 0
Abstract
MicroRNA-21 (miRNA-21) expression is increased in patients with kidney disease, and polysaccharides provide the structural scaffolding of the glomerular and tubular basement membranes.We investigated whether the induction of renal injury by the industrial toxic chemical thioacetamide (TAA) can dysregulate the kidney miRNA-21/SIRT1/NF-κB axis as well as the structural polysaccharide content of the kidney tissue, and whether treatment with the polyphenolic compound resveratrol can inhibit these adverse effects.Kidney injury was induced in rats by TAA (200 mg/kg) injections. The protective group of rats was pre-treated with resveratrol (20 mg/kg) prior to kidney injury and subsequently kept on resveratrol until culled.TAA intoxication caused a significant (p < 0.0001) modulation in kidney and blood levels of miRNA-21, the tissue renoprotective molecule SIRT1, NF-κB p65, kidney structural polysaccharides, the macrophage biomarker cluster of differentiation 68 (CD68), tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, hypernatremia, urea, and creatinine, as well as albuminuria that were significantly (p ≤ 0.0187) protected by resveratrol. Furthermore, a significant correlation between the miRNA-21/SIRT1/NF-κB axis, structural polysaccharides, renal fibrosis, and renal injury biomarkers were observed.These findings demonstrate an association between renal injury induced by TAA intoxication and the dysregulation of the kidney miRNA-21/SIRT1/NF-κB axis and polysaccharide levels while being protected by resveratrol.
期刊介绍：
Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology
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