Pharmacological and Toxicological Effects of Diphenyl Ditelluride Administered by Oral Route

Based on pharmacological and toxicological properties of organotellurium compounds, the present study investigated the effect of diphenyl ditelluride on pharmacological and toxicological assays. Mice (25 – 35 g) and rats (180 – 250 g) received a single oral dose of diphenyl ditelluride (75-500 mmol /Kg; 0.25-3 mmol /Kg, respectively) or vehicle (canola oil) and were observed up to 72 h to determine the lethal potential of diphenyl ditelluride (LD₅₀). After 72 h of exposure, animals were slightly anesthetized for blood collection and plasma was obtained and used for biochemical assays. In addition, all groups were killed and the liver and kidney were removed for assay of thiobarbituric acid-reactive species (TBARS) and d-ALA-D (aminolevulinate dehydratase) activity.  Data were analyzed statistically by one-way ANOVA, followed by Duncan’s Multiple Range Test when appropriate. In the present study, we found that LD₅₀ for diphenyl ditelluride administered by oral route in rats and mice were estimated to be 0.9 and 354 mmol /Kg, respectively. Rats and mice treated with LD₅₀ for diphenyl ditelluride presented hepatic δ- ALA-D activity inhibited. Renal δ- ALA-D of rats treated with LD₅₀ for diphenyl ditelluride was inhibited, whereas in mice the activity was not changed. Hepatic and renal TBARS levels of mice did not differ when compared to the levels found in control animals at all doses tested. Conversely, renal and hepatic TBARS levels in rats increased with 0.75 and 0.9 μmol/Kg of diphenyl ditelluride, respectively. Mice treated (p.o) with 300 μmol/Kg demonstrated an increase in plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities, as well as creatinine levels, whereas in rats none difference was observed. Diphenyl ditelluride also produced a significant decrease in plasma cholesterol levels when administered (150 μmol/Kg) in mice. In addition, none of diphenyl ditelluride tested doses changed plasma triglycerides and urea levels in mice. Rats treated (p.o) with 0.75 μmol/Kg produced a significant increase in urea levels, whereas plasma triglycerides, creatinine and cholesterol levels did not differ at all doses tested. In conclusion, this is a promising compound for more detailed pharmacological studies involving organotellurium compounds.