Toxicity of organochalcogens in human leukocytes is associated, but not directly related with reactive species production, apoptosis and changes in antioxidant gene expression

Abstract

Selenium (Se) containing organic compounds, such as ebselen (Ebs) and diphenyl diselenide [(PhSe)2], have been used as pharmacological agents due to their antioxidant properties. Tellurium (Te) does not have any biological function in mammals, but Te-containing organic compounds, such as diphenyl ditelluride [(PhTe)2], has been used both as an antioxidant or neurotoxic agent. At high concentrations, these compounds cause toxicity by oxidising thiol and selenol groups of proteins. Here, we analysed whether these compounds could modulate reactive species (RS) production, apoptosis and antioxidant gene expression profile of some selenoproteins and antioxidant enzymes or transcription factors in leukocytes isolated from human blood. Since no data is available about their accumulation in isolated leukocytes, we determine their concentration in the cells by CG-MS. Apoptosis (propidium iodide) and RS production (dichloro fluorescein) were determined by flow cytometry. The expression of CAT, SOD1, GPX3, GPX4, TRXR1, and NFLE2L2 genes were analysed by RT-PCR. (PhTe)2 was the only compound able to increase apoptosis rate. (PhSe)2 altered the expression of CAT and SOD1, and this was associated with a high RS production. All compounds decreased the expression of GPX3 but did not alter GPX4 and TRXR1 expression. All compounds decreased NFE2L2 expression (Ebs > (PhTe)2> (PhSe)2). We hypothesise that the toxicity induced by these organochalcogens is not directly related to their ability of inducing RS production.