Study of Antioxidant Activity and Potential Toxicity of 1-Buthyltelurenyl-2-methylthioheptene

The aim of the present study was to evaluate pharmacological and toxicological properties of 1-buthyltelurenyl-2-methylthioheptene (compound 1). The level of lipid peroxides in the reaction was measured by the method of Ohkawa et al. (1979) using MDA (malondialdehyde) as an external standard. The reactive species (RS) measurement were determined by a spectrofluorimetric method, using 2’,7’- dichlorofluorescein diacetate (DCHF-DA) assay.  Free-SH groups were determined according to Ellman (1959). δ-ALA-D (aminolevulinate dehydratase) activity was assayed by the method of Sassa (1982) by measuring the rate of product (porphobilinogen, PBG) formation. Data were analyzed statistically by one-way ANOVA, followed by Duncan’s Multiple Range Test when appropriate. In vitro, compound 1 at 1 mM was effective in reducing lipid peroxidation induced by FeSO₄ and EDTA. Furthermore, compound 1 at 100 mM decreased reactive species (RS) in the fluorimetric assay. Compound 1 demonstrated neither thiol peroxidase nor thiol oxidase activity and did not change δ-ALA-D (δ- aminolevulinate dehydratase) activity (10 - 400 mM). In vivo, rats were treated with a single oral dose of compound 1 (0.5, 5, 50, 75, 100 and 200 mmol/Kg) or vehicle (1mL/Kg, canola oil) and were observed up to 72 h to determine LD₅₀ of compound 1 which was 65.1 μmol/Kg. The rats treated with compound 1 did not reveal any motor impairment in the open field task. After 72h, rats were killed and the liver, kidney, brain and spleen were removed for ex vivo assays. Hepatic, renal and cerebral lipid peroxidation in treated rats did not differ from that of in control rats. Conversely, 0.5 mmol/Kg of compound 1 decreased lipid peroxidation in spleen. δ-ALA-D activity in liver and spleen was inhibited in rats treated with the higher dose of compound 1 but no significant differences were detected in renal δ-ALA-D activity. The high doses of compound 1 (50-75 μmol/Kg) caused an increase in plasma AST (aspartate aminotransferase)  and ALT (alanine aminotransferase) activities, as well as, urea and creatinine levels. Conversely, this compound produced a significant decrease in plasma triglycerides levels and none of the doses tested changed cholesterol level. In conclusion, this is a promising compound for more detailed pharmacological studies involving organotellurium compounds.