Effects of antimony on mitochondrial function and protein thiol and adenine nucleotide status in cultured cardiac myocytes.
Tirmenstein-MA; Wey-HE; Mathias-PI; Toraason-M
Toxicologist 1995 Mar; 15(1):310-311
Antimony and antimony containing compounds are used in the manufacture of paints, pigments, ceramics, pyrotechnics, fire retardants and glass. Exposure to antimony containing compounds has been associated with cardiac toxicity in man and experimental animals. In a previous study in our laboratory, we demonstrated that potassium antimonyl tartrate (PAT) depletes cellular glutathione and induces oxidative stress and toxicity in rat cardiac myocytes. In the present study, cardiac myocytes isolated from neonatal rats and cultured for two days were used to further examine the mechanism of PAT-induced toxicity. Exposure to 100 uM PAT for 4 hrs reduced the mitochondrial membrane potential by about 30% as measured by rhodamine 123 retention. The effects of PAT on cellular ATP levels were assessed by measuring total adenine nucleotides by HPLC with uv detection. PAT produced a concentrationdependent reduction in ATP levels. Concentrations of 50 and 100 uM PAT reduced cellular ATP levels by 20% and 70% respectively after 4 hrs. However, ATP was not depleted after a 2 hr exposure to these concentrations of PAT. PAT-induced losses of ATP could not be accounted for by reciprocal increases in either ADP or AMP concentrations. The effects of PAT on protein thiol levels were examined by reacting cellular proteins with the fluorescent thiol labeling probe monobromobimane. At a concentration of 100 ILM, PAT produced a 40% reduction in protein thiols after 4 hrs. A significant reduction (15%) in protein thiols was also seen following a 4 hr exposure to 50 uM PAT. These results suggest that PAT has deleterious effects on mitochondrial integrity, cellular thiol status and the energy status of the cell.
Exposure-assessment; Exposure-limits; Cellular-reactions; Animal-studies; Laboratory-animals; Calcium-compounds; Antimony-compounds; Myocardial-disorders; Cardiovascular-disease; Cardiovascular-system-disorders; Cardiopulmonary-system-disorders
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland