Phosphotriesterase decreases paraoxon toxicity in mice.
The effect of phosphotriesterase (PTE) on the ip toxicity of paraoxon was studied in mice. The PTE preparation (0.1 ml; paraoxon-hydrolyzing activity, 1.5 mumol/min) was given iv. Cholinesterase activities were measured 2 hr after paraoxon administration. The PTE treatment, given 10 min before paraoxon, did not protect serum cholinesterase (ChE) against the inhibiting effect of paraoxon, but it clearly prevented the decrease of the brain ChE activity. In PTE-nontreated animals ChE was reduced by 60% at the paraoxon dose of 0.5 mg/kg, whereas in PTE-treated mice a significant reduction was not seen until a paraoxon dose of 2.0 mg/kg. The iv injection of PTE did prevent the decrease in brain ChE activity by paraoxon, when it was administered before or immediately after the paraoxon. PTE, injected 15 min after paraoxon, resulted in a minor protection in the brain ChE activities. The iv injection of PTE increased the serum paraoxon-hydrolyzing activity up to 5.1-fold. When the same amounts of PTE were administered ip, im, or sc, the increases in the hydrolyzing activities were 4.7-, 2.5-, and 1.8-fold, respectively. The activities returned to the normal level within 24 hr after the PTE. The elimination half-life of the activity of PTE administered iv was approximately 5.5 hr. In conclusion, PTE substantially prevents the toxicity of paraoxon in mice by hydrolyzing paraoxon in circulation.
Kaliste-Korhonen
E
E
National Laboratory Animal Center, University of Kuopio, Finland.
Ylitalo
P
P
Hänninen
O
O
Raushel
F M
FM
D000818:Animals; D043303:Aryldialkylphosphatase; D001769:Blood / Q000187:drug effects; D004333:Drug Administration Routes; D004347:Drug Interactions; D006868:Hydrolysis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010261:Paraoxon / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010744:Phosphoric Monoester Hydrolases / Q000008:administration & dosage / Q000494:pharmacology*; D013379:Substrate Specificity
D010744:Phosphoric Monoester Hydrolases; D043303:Aryldialkylphosphatase; D010261:Paraoxon