A biochemical and toxicological study with diethyl 2-phenyl-2-tellurophenyl vinylphosphonate in a sub-chronic intraperitoneal treatment in mice

Life Sci. 2007 Apr 24;80(20):1865-72. doi: 10.1016/j.lfs.2007.02.033. Epub 2007 Mar 1.

Abstract

Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with low toxicity after subcutaneous administration in mice. This study evaluated possible in vivo and ex vivo toxicological effects of daily injections of DPTVP for 12 days in mice, using the intraperitoneal administration. This route potentially increases the pharmacokinetics of absorption, distribution, metabolism and toxicity of DPTVP. Treatment with DPTVP (0, 30, 50, 75, 100, 250, 350 or 500 micromol/kg) were not associated with mortality or body weight loss. Nevertheless, the liver and liver-to-body weight ratio increased in groups treated with 350 and 500 micromol/kg of DPTVP. However, plasmatic aspartate and alanine aminotransferase activities (classical markers of hepatotoxicity) were not increased after diethyl-2-phenyl-2-tellurophenyl vinylphosphonate administration. Hepatic, renal and cerebral thiobarbituric acid reactive substances (TBARS), delta-ALA-D activity and Vitamin C levels were not modified after DPTVP treatment. Renal and hepatic superoxide dismutase (SOD) and catalase (CAT) were unchanged after DPTVP treatment. Conversely, SOD activity significantly increased in brain in groups treated with 50, 75, 100 and 500 micromol/kg of DPTVP treated groups. Our findings corroborates that brain is a potential target for organochalcogen action. The absence of severe overt signs of toxicity after sub-chronic exposure to DPTVP reinforces the necessity for more detailed pharmacological studies concerning this new organotellurium compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism
  • Body Weight / drug effects
  • Brain / metabolism*
  • Catalase / metabolism
  • Drug Administration Routes
  • Glutathione / metabolism
  • Infusions, Parenteral
  • Kidney / metabolism*
  • Liver / metabolism*
  • Mice
  • Organ Size / drug effects
  • Organ Size / physiology
  • Organometallic Compounds / pharmacokinetics*
  • Organophosphonates / pharmacokinetics*
  • Porphobilinogen Synthase / metabolism
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism*
  • Tissue Distribution
  • Transaminases / metabolism

Substances

  • Organometallic Compounds
  • Organophosphonates
  • Thiobarbituric Acid Reactive Substances
  • diethyl 2-phenyl-2 tellurophenyl vinylphosphonate
  • Catalase
  • Superoxide Dismutase
  • Transaminases
  • Porphobilinogen Synthase
  • Glutathione
  • Ascorbic Acid