title: Interaction of monocrotophos and its novel thion analogues with microsomal cytochrome P-450: in vivo and in vitro studies in rat.
abstract: The binding of monocrotophos (MCP) and its two thion analogues (coded as RPR-II and RPR-V) to rat hepatic microsomal cytochrome P-450 (HMC) were investigated in vitro by difference spectroscopy. These three organophosphorus insecticides were found to bind stoichiometrically to HMC with very high affinity (Ks 34-50 microM). RPR-V showed the highest binding affinity followed by RPR-II and MCP. Association of these compounds with HMC occurred within 2 min of addition in the cuvette and therefore, appeared to be tight binding ligands of cytochrome P-450. In vivo studies at equitoxic doses of the three compounds 24 h after oral treatment in rats revealed that they all caused reduction in MC content in liver, lung, kidney and brain, as against induction in cardiac and splenic cytochrome P-450. These in vivo results suggest organ specificity in modulating the microsomal cytochrome P-450 (MC) content of hepatic and extra-hepatic tissues by the three compounds. Apparently, their binding affinity with HMC is strongly correlated with their LD50 value and has a substantial co-relationship with the cytochrome P-450 level in the liver.
authors.affiliation: Toxicology Division, Indian Institute of Chemical Technology, Hyderabad.
authors.forename: M K
authors.initials: MK
authors.lastname: Siddiqui
authors.forename: M
authors.initials: M
authors.lastname: Mahboob
authors.forename: M
authors.initials: M
authors.lastname: Mustafa
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D007928:Lethal Dose 50; D008024:Ligands; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008999:Monocrotophos / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013154:Spleen / Q000201:enzymology
chemical_list: D008024:Ligands; D008999:Monocrotophos; D003577:Cytochrome P-450 Enzyme System