Hepatic and extra hepatic glutathione depletion and glutathione-S-transferase inhibition by monocrotophos and its two thiol analogues.
Effect of monocrotophos (MCP) and its thiol analogues (coded as RPR-2 and RPR-5) on hepatic and extra-hepatic glutathione (GSH) depletion and glutathione-S-transferase (GST) inhibition was studied at 0.96, 1.23 and 3.0 mg/kg respectively 24 h after medication in rats. All the three compounds caused tissue specific depletion of GSH from hepatic and extra-hepatic tissues. Cytosolic GST activity was significantly inhibited in all the tissues, MCP being the most potent inhibitor. Both in vitro and in vivo data indicate that hepatic GST inhibiting potential of the three compounds lies in the order MCP greater than RPR-5 greater than RPR-2. In vitro effect of 3 compounds on GSH activation kinetics of GST demonstrate competitive inhibition by MCP and non-competitive inhibition by the two analogues. However, CDNB activation kinetics of the enzymes revealed mixed inhibition by all 3 compounds. The present study suggests that monocrotophos and its thiol analogues may bring about physiological upsets by altering GSH and GST dependent events in different tissues of exposed organisms.
Siddiqui
M K
MK
Toxicology Unit, Indian Institute of Chemical Technology, Hyderabad.
Mahboob
M
M
Mustafa
M
M
D000284:Administration, Oral; D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008999:Monocrotophos / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014018:Tissue Distribution
D007306:Insecticides; D013438:Sulfhydryl Compounds; C066790:RPR 5; C066789:RPR 2; D008999:Monocrotophos; D005982:Glutathione Transferase; D005978:Glutathione