Sub-acute administration of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate induces toxicity and oxidative stress in mice: unexpected effects of N-acetylcysteine

Abstract

The organic tellurium compound (S)-dimethyl 2-(3-(phenyltellanyl) propanamide) succinate (TeAsp) exhibits thiol-peroxidase activity that could potentially offer protection against oxidative stress. However, data from the literature show that tellurium is a toxic agent to rodents. In order to mitigate such toxicity, N-acetylcysteine (NAC) was administered in parallel with TeAsp during 10 days. Mice were separated into four groups receiving daily injections of (A) vehicle (PBS 2.5 ml/kg, i.p. and DMSO 1 ml/kg, s.c.), (B) NAC (100 mg/kg, i.p. and DMSO s.c.), (C) PBS i.p. and TeAsp (92.5 μmol/kg, s.c), or (D) NAC plus TeAsp. TeAsp treatment started on the fourth day. Vehicle or NAC-treated animals showed an increase in body weight whereas TeAsp caused a significant reduction. Contrary to expected, NAC co-administration potentiated the toxic effect of TeAsp, causing a decrease in body weight. Vehicle, NAC or TeAsp did not affect the exploratory and motor activity in the open-field test at the end of the treatment, while the combination of NAC and TeAsp produced a significant decrease in these parameters. No DNA damage or alterations in cell viability were observed in leukocytes of treated animals. Treatments produced no or minor effects on the activities of antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase, whereas the activity of the thioredoxin reductase was decreased in the brain and increased the liver of the animals in the groups receiving TeAsp or TeAsp plus NAC. In conclusion, the toxicity of TeAsp was potentiated by NAC and oxidative stress appears to play a central role in this process.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-182) contains supplementary material, which is available to authorized users.

Organotellurium scaffolds for mass cytometry reagent development

“…Microorganisms have been found to methylate inorganic tellurium to volatile or ionic species for excretion. 17,18 Here we describe the synthesis, aqueous/aerobic stability, and in vitro toxicity of a series of alkyl telluroethers and tellurophene functional groups. 7 However the number reports of cellular studies involving aryl, vinylic, alkynyl and alkyl telluroethers in biological systems are increasing.…”

“…15,16 Recent murine studies have shown diverse effects from the expected toxicity of an amino acid-based aryl telluroether to increased memory in mice treated with an alkyl telluroether. 17,18 Here we describe the synthesis, aqueous/aerobic stability, and in vitro toxicity of a series of alkyl telluroethers and tellurophene functional groups. We hypothesized that the organotellurium exhibiting the most favourable properties with respect to these three criteria would be an improved mass tag component for the next generation of MC probes.…”