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The Influence of Acetylcholinesterase Reactivators on Selected Hepatic Functions in Rats
Author(s) -
Pejchal Jaroslav,
Osterreicher Jan,
Kuca Kamil,
Jun Daniel,
Bajgar Jiri,
Kassa Jiri
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00249.x
Subject(s) - multidrug resistance associated protein 2 , pyridinium , acetylcholinesterase , chemistry , pharmacology , in vivo , endocrinology , medicine , transporter , biochemistry , enzyme , biology , medicinal chemistry , gene , atp binding cassette transporter , microbiology and biotechnology
The aim of our study was to evaluate the impact of acetylcholinesterase reactivators – K027 [1‐(4‐carbamoyl pyridinium)‐3‐(4‐hydroxyiminomethyl pyridinium) propane dibromide], HI‐6 [1‐(4‐carbamoylpyridinium)‐3‐(2‐hydroxyimino methylpyridinium) oxapropane dichloride] and obidoxime [1,3‐bis(4‐hydroxyiminomethyl pyridinium)oxapropane dichloride] on hepatic functions in vivo . Male Wistar rats were randomly divided to seven groups and intramuscularly administered with saline and acetylcholinesterase reactivators (K027, HI‐6 and obidoxime) at doses of 5% LD 50 and 50% LD 50 . Liver tissue samples were taken 24 hr after administration. Histochemical detection of lipid droplets and immunohistochemical detection of multidrug resistance protein 2 (Mrp2) were provided. Lipid droplet count in rat liver did not show any significant differences in animals administered with K027, HI‐6 and obidoxime in comparison with the control group. Mrp2 protein expression significantly decreased when animals were administered with K027 at a dose of 50% LD 50 and HI‐6 and obidoxime at doses of 5% LD 50 and 50% LD 50 , when compared to the controls. No statistical differences of Mrp2 expression were measured when animals were administered with K027 at a dose of 5% LD 50 in comparison with control animals. We found impaired hepatic transporter function after administration of HI‐6, obidoxime and higher concentration of K027, which might be the underlying mechanism of acetylcholinesterase reactivators’ hepatotoxicity.