Selenite and ebselen supplementation attenuates d-galactose-induced oxidative stress and increases expression of SELR and SEP15 in rat lens

Abstract

Selenite and ebselen supplementation has been shown to possess anti-cataract potential in some experimental animal models of cataract, however, the underlying mechanisms remain unclear. The present study was designed to evaluate the anti-cataract effects and the underlying mechanisms of selenite and ebselen supplementation on galactose induced cataract in rats, a common animal model of sugar cataract. Transmission electron microscopy images of lens fiber cells (LFC) and lens epithelial cells (LEC) were observed in D-galactose-induced experimental cataractous rats treated with or without selenite and ebselen, also redox homeostasis and expression of proteins such as selenoprotein R (SELR), 15kD selenoprotein (SEP15), superoxide dismutase 1 (SOD1), catalase (CAT), β-crystallin protein, aldose reductase (AR) and glucose-regulated protein 78 (GRP78) were estimated in the lenses. The results showed that D-galactose injection injured rat lens and resulted in cataract formation; however, selenite and ebselen supplementation markedly alleviated ultrastructural injury of LFC and LEC. Moreover, selenite and ebselen supplementation could mitigate the oxidative damage in rat lens and increase the protein expressions of SELR, SEP15, SOD1, CAT and β-crystallin, as well as decrease the protein expressions of AR and GRP78. Taken together, these findings for the first time reveal the anti-cataract potential of selenite and ebselen in galactosemic cataract, and provide important new insights into the anti-cataract mechanisms of selenite and ebselen in sugar cataract.

Transcriptional Regulation of Selenoprotein F by Heat Shock Factor 1 during Selenium Supplementation and Stress Response

“…Several selenium compounds have been reported to be able to up-regulate SELENOF expression, including selenate, selenite, methylseleninic acid, and selenomethionine [28,29]. These selenium compounds, except selenate, are redox-reactive.…”

Emerging roles of ER-resident selenoproteins in brain physiology and physiopathology

“…On the basis of their previous studies demonstrating an interaction between SELENOF and UGGT, the authors suggested that the phenotype observed is due to an improper folding of lens proteins caused by SELENOF deficiency. Dai and collaborators (2016) showed the protective effect of selenite supplementation against d -galactose-induced cataract in rats, an effect which was linked to an increase in SELENOF expression [ 77 ]. More recently, a yeast two-hybrid system which was used to identify SELENOF partners in a human fetal brain cDNA library revealed an interaction between SELENOF and retinol dehydrogenase 11 (RDH11), an enzyme involved in vitamin A metabolism.…”

Role of Selenoprotein F in Protein Folding and Secretion: Potential Involvement in Human Disease

“…In the liver of selenium-supplemented growing lambs, SELENOF mRNA was found to be upregulated [ 28 ]. Furthermore, selenium can prevent the downregulation of SELENOF mRNA which is caused by toxicants or oxidative stress [ 29 , 30 , 31 ].…”