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.
Pejchal
Jaroslav
J
Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
Osterreicher
Jan
J
Kuca
Kamil
K
Jun
Daniel
D
Bajgar
Jiri
J
Kassa
Jiri
J
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism; D007928:Lethal Dose 50; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009768:Obidoxime Chloride / Q000737:chemistry / Q000633:toxicity*; D010091:Oximes / Q000737:chemistry / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
C481758:1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide; D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; C022870:asoxime chloride