Effect of PON1 on dichlorvos toxicokinetics.

Abstract

OBJECTIVES:

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.

CONCLUSION:

PON1 can decrease the amount of dichlorvos that entered the blood, lowered the peak concentration and relieved clinical signs.

• Authors: Na-Na Wang, Li Yuan, Heng Dai, Zhen-Kun Han, Min Zhao
• Journal: Emergency medicine journal : EMJ (Emerg Med J) Vol. 28 Issue 4 Pg. 313-5 (Apr 2011) ISSN: 1472-0213 [Electronic] England
• PMID: 20581384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholinesterase Inhibitors
• Dichlorvos
• Aryldialkylphosphatase

Topics

• Animals
• Area Under Curve
• Aryldialkylphosphatase (administration & dosage, pharmacology)
• Cholinesterase Inhibitors (blood, pharmacokinetics, poisoning)
• Chromatography, High Pressure Liquid
• Dichlorvos (blood, pharmacokinetics, poisoning)
• Male
• Mass Spectrometry
• Poisoning (drug therapy)
• Random Allocation
• Rats
• Rats, Wistar