Click for new scientific resources and news about Corona[COVID-19]

Paper Information

Title: 

A SEARCH FOR MOLECULAR MECHANISMS RESPONSIBLE FOR PHENYLENEDIAMINE COMPOUNDS INDUCED CYTOTOXICITY

Type: SPEECH
Author(s): POURAHMAD J.,SHAKOORI A.
 
 
 
Name of Seminar: IRANIAN CONGRESS OF TOXICOLOGY
Type of Seminar:  CONGRESS
Sponsor:  SOCIETY OF TOXICOLOGY
Date:  2004Volume 8
 
 
Abstract: 

Muscle necrosis induced by various phenylenediamine derivatives has been correlated with their autoxidation vate. In the following we performed a more detailed investigation of the cytotoxic mechanisms using a model system of isolated hepatocyts and 2, 3, 5, 6-tetramethylparaphenylenediamine.
The agents or enzymes responsible for the metabolic activation of phenylenediamine compounds are not know. We have now shown that under aerobic conditions, phenylenediamine induced cytotoxicity and ROS formation were markedly increased by inactivating DT diaphorase but were prevented by a subtoxic concentration of mitochondrial respiratory inhibitor cyanide. This suggest that the H2O2 generation attributed to futile two electron redox cycle involving oxidation of phenylenediamine to the corresponding diimine by the mitochondrial electron transfer chain and re-reduction by the DT diaphorase. The subcellular organelle oxidative stress effects leading to cytotoxicity are not known. Hepatocyte mitochondrial membrane potential was only slightly decreased by phenylenediamine before cytotoxicity ensued. However phenylenediamine induced lysosomal damage and hepatocyte protease activation. Endocytosis inhibitors, lysosomotropic agents or lysosomal protease inhibitors also prevented phenylenediamine induced cytotoxicity. GSH oxidation and mixed protein disulphide formation also preceded cytotoxicity. Furthermore desferoxamine (a ferric chelator), antioxidants or ROS scavengers (catalase, mannitol, TEMPOL or dimethylsulfoxide) prevented paraphenylenediamine cytotoxicity. It is concluded that H2O2 reacts with lysosomal Fe2+ to from ‘ROS’ which causes lysosomal lipid peroxidation, membrance disruption, protease release and cell death.

 
Keyword(s): 
 
 
Yearly Visit 55   tarjomyar
 
Latest on Blog
Enter SID Blog