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Paper Information

Title: 

MOLECULAR MECHANISMS RESPONSIBLE FOR ARSENITE INDUCED CYTOTOXICITY

Type: SPEECH
Author(s): POURAHMAD J.,RABIEI M.,O BRIEN P.J.
 
 
 
Name of Seminar: IRANIAN CONGRESS OF TOXICOLOGY
Type of Seminar:  CONGRESS
Sponsor:  SOCIETY OF TOXICOLOGY
Date:  2004Volume 8
 
 
Abstract: 

In the following we have investigated the cytotoxic mechanisms of the arsenite AsO2-. Arsenite cytotoxicity was associated with little oxidative stress and lysosomal damage did not occur. However arsenite cytotoxicity was associated with a loss of mitochondrial membrane potential which was inhibited by the ATP generators fructose, xylitol and glutamine. Arsenite induced cytotoxicity, mitochondrial membrane potential decline and also ROS formation were significantly increased by inactivating hepatocyte methionine synthase or hepatocyte methyl transferase but were prevented by methyl donors such as betaine, methionine, folic acid and methylcobalamine and this suggests that arsenite is detoxified by reductive methylation. In conclusion arsenite induced cytotoxicity could be attributed to mitochondrial toxicity and ATP depletion.

 
Keyword(s): HEPATOCYTE, ARSENITE, CYTOTOXICITY, METHYLATION, MITOCHONDRIA
 
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