Se deficiency induces renal pathological changes by regulating selenoprotein expression, disrupting redox balance, and activating inflammation.

Abstract

Selenium (Se) is closely associated with kidney disease, and renal injury often occurs together with hyposelenemia. This study was designed to reveal the mechanism underlying renal injury induced by Se deficiency in pigs. Twenty-four castrated male Yorkshire pigs were divided into two groups fed either a Se-deficient diet (0.007 mg Se per kg) or a Se-adequate diet (0.3 mg Se per kg). Serum and kidney samples were collected at the 16th week of the trial, processed, and analyzed for serum biochemistry, Se concentration, kidney index markers, histology, selenoprotein mRNA expression, redox status, and inflammatory cytokines. Dietary Se deficiency induced kidney injury, decreased (P < 0.05) Se concentrations, and increased (P < 0.05) kidney index and serum blood urea nitrogen, creatinine, and carbon dioxide values. Histological analysis indicated that Se deficiency induced inflammatory lesions and renal tubular atrophy in the renal medulla. Se deficiency downregulated (P < 0.05) nine selenoprotein genes (GPX1, SELENOW, SELENOH, SELENOP, GPX3, TXNRD2, SELENOI, SELENON, and SELENOM) and upregulated (P < 0.05) SEPHS2 in the kidneys. Se deficiency decreased (P < 0.05) the activity of glutathione peroxidase, thioredoxin reductase, and catalase, as well as the hydroxyl radical inhibition capacity, and increased (P < 0.05) the content of malondialdehyde and nitric oxide. Se deficiency increased (P < 0.05) the expression of the transcription factors NF-κB and HIF-1α, and regulated inflammatory cytokines. Se deficiency increased (P < 0.05) the expression of IL-6, IL-8, IL-12, IL-17, and cyclooxygenase-2, and decreased (P < 0.05) the expression of IL-10, IL-13, and TGF-β. These results indicated that Se deficiency induces kidney injury through the regulation of selenoproteins, oxidative stress, and inflammation.