Dietil-2-fenil-2-telurofenil vinilfosfonato: um composto orgânico de telúrio com atividade antioxidante in vitro e com baixa toxicidade in vivo em camundongos

Abstract

Despite the growing use of organotellurium compounds in chemical and biochemical fields, there is no great concern about their toxicity until now. Diethyl-2-phenyl-2-tellurophenyl vinylphospnonate is a β-organochalcogenyl vinylphosphonate that is a usefull tool for organic synthesis, but no toxicological and pharmacological studies about it are described in the literature. In this study, we investigated, in vitro, the possible antioxidant activity and toxic properties of this compound, and evaluated its putative toxicological effects through biochemical parameters, ex vivo, after subchronic administration by the subcutaneous and intraperitoneal vias. As other organotellurium compounds, the diethyl-2-phenyl-2-tellurophenyl vinylphosphonate also was able to oxidize SH groups from DTT, as well as to inhibit hepatic, renal and cerebral δ- ALA-D in vitro, however, at relatively high concentrations. The antioxidant activity was also observed in brain, liver and kidney, at very low concentrations, and its ability to reduce the lipid peroxidation- induced by Fe+2 was comparable to the antioxidant organotellurium compound diphenyl ditelluride. In vivo, diethyl-2-phenyl-2-tellurophenyl vinylphosphonate was very low toxic to mice that received twelve daily injections through subcutaneous and intraperitoneal via, different from the animals that received diphenyl ditelluride s.c, which died after the fourth day of treatment. Ex vivo, the δ- ALA-D activity in liver, kidney and brain were not affected by these treatments with diethyl-2-phenyl-2-tellurophenyl vinylphosphonate, In addition, the i.p. treatment did not affect the survival of the treated mice. The body weight of treated mice did not change; however, the liver weight was increased in the animals that received the major doses, probably due to the increase in the metabolization; in fact, no tissue damage was detected, since plasmatic activities of AST and ALT were not altered. The biochemical parameters of oxidative stress that were evaluated, TBARS formation, Vitamin E levels, GSH/GSSG ratio, SOD and catalase activities, were not changed in liver and kidney, nevertheless, in brain, SOD activity significantly increase, whereas catalase activity tended to increase, at the intermediary doses, indicating that this tissue would be suffering some alteration due to the administration of the organotellurium compound. Taken together, these data suggest that this organotellurium compound is promising for further pharmacological studies, once that it does not has pronounced toxic effects, but has antioxidant properties.