Effect of PON1 on dichlorvos toxicokinetics.
OBJECTIVE
To provide toxicokinetic and clinical evidence of the hydrolytic effect of paraoxonase-1 (PON1) on acute organophosphate poisoning in rats.


METHODS
40 male Wistar rats were randomised into four equal groups. Dichlorvos administration group (A group) underwent dichlorvos injection (dissolved in corn oil) using intraperitoneal (ip) dose of 10 mg/kg. PON1 pretreatment group (B group) was injected with PON1 in the tail vein (intravenous), dose 9600 U/kg, 30 min prior to dichlorvos administration. In the treatment group (C group), atropine 0.05 mg/kg and pyraloxime chloride (PAM-CI) 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Finally, in the co-treatment group (D group), PON1 was injected intravenously with a dose of 9000 U/kg 30 min prior to dichlorvos administration; atropine 0.05 mg/kg and PAM-CI 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Blood was collected after administration. Plasma dichlorvos concentration was detected by liquid chromatography-mass spectra (LC-MS) method and clinical signs were observed. Toxicokinetic parameters were calculated in a statistical moment model.


RESULTS
AUC (0→∞) in group B was statistically different from that in groups A and C (p<0.05), while it was not different from group D (p>0.05); there was no statistical difference between group A and group C (p>0.05). The statistical results of Cmax were the same as those of AUC (0→∞). There were no differences of MRT between four groups (p>0.05). Clinical signs can be improved by PON1 and atropine + PAM-CI, and co-treatment can relieve signs more effectively.


CONCLUSIONS
PON1 can decrease the amount of dichlorvos that entered the blood, lowered the peak concentration and relieved clinical signs.
Wang
Na-Na
NN
Emergency Department, Shengjing Hospital of China Medical University, Shenyang, China.
Yuan
Li
L
Dai
Heng
H
Han
Zhen-Kun
ZK
Zhao
Min
M
D000818:Animals; D019540:Area Under Curve; D043303:Aryldialkylphosphatase / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D002851:Chromatography, High Pressure Liquid; D004006:Dichlorvos / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D008297:Male; D013058:Mass Spectrometry; D011041:Poisoning / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D004006:Dichlorvos; D043303:Aryldialkylphosphatase