The influence of acetylcholinesterase reactivators on selected hepatic functions in rats

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.