Effects of arsenite pretreatment on the acute toxicity of parathion.
Parathion (PA) is a phosphorotioate pesticide requiring P-450-mediated oxidations to become activated to paraoxon, or to be metabolised to its less toxic metabolites. On the other hand, sodium arsenite [As(III)] markedly decreases total hepatic P-450 content and dependent monoxygenase activities. Our aim was to determine the effects of As(III) pretreatment on the acute toxicity of PA and its possible relationship with the effects of As(III) on P-450-dependent monooxygenase activities. Adult male Wistar rats were pretreated with As(III) (5.6 mg As(III)/kg, s.c.), and 24 h later given PA (5 to 20 mg/kg, per os). As(III) pretreatment increased the acute toxicity of PA, reducing 38% its median lethal dose (LD50) from 11.68 to 7.21 mg PA/kg. In addition, As(III) pretreatment further decreased the inhibitory effect of PA on brain acetylcholinesterase activity, reducing 33% the median inhibitory dose (ID50) from 3.44 to 2.31 mg PA/kg. whereas As(III) alone had no significant effects. As(III) decreased the P-450 content to 87% of control values, reduced EROD activity to 74% and BROD activity to 41%; PA produced no significant effects on these parameters, whereas the joint administration of As(III)+ PA produced effects similar to those of As(III). PROD activity was reduced to 36% of control value by PA, whereas As(III) alone produced no significant effects. However, As(III) pretreatment apparently protected against the inhibition of CYP2B1-mediated PROD activity produced by PA, since PROD values were similar to those of control animals. Our results also indicated that the increase in PA toxicity caused by As(III) pretreatment, could also be related to the CYP2B2 isoform, since decreases in CYP2B2-dependent BROD activity were observed in both As(III) and As(III) + PA groups, but not in PA-treated animals, suggesting that CYP2B2 is involved in PA detoxification.
Siller
F R
FR
Departamento de Farmacologia y Toxicología, Centro de Investigación yde Estudios Avanzados del I.P.N., México.
Quintanilla-Vega
B
B
Cebrián
M E
ME
Albores
A
A
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001711:Biotransformation; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010278:Parathion / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D018053:Arsenites; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D007527:Isoenzymes; D010278:Parathion; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1