Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

• Authors: Radosław Świercz , Piotr Lutz , Sławomir Gralewicz , Zofia Grzelińska , Joanna Piasecka-Zelga , Wojciech Wąsowicz

Abstracts

EN

Background: Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentraion (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steoid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. Material and Methods: The purose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. Conclusion: The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

Keywords

EN

chlorfenvinphos; metyrapone; cholinesterase; corticosterone

• Publisher: Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
• Journal: International Journal of Occupational Medicine and Environmental Health
• Year: 2013
• Volume: 26
• Issue: 4
• Pages: 636-646

Dates

published

2013

Contributors

author

Radosław Świercz

• Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland

author

Piotr Lutz

• Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland

author

Sławomir Gralewicz

• Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland

author

Zofia Grzelińska

• Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland

author

Joanna Piasecka-Zelga

• Laboratory for Testing Pharmaceuticals and Veterinary Products, GMP Quality System, Nofer Institute of Occupational Medicine, Łódź, Poland

author

Wojciech Wąsowicz

• Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland

Identifiers

DOI

10.2478/s13382-013-0131-1

Biblioteka Nauki

2179137