Effect of combined fenthion and cimetidine use in rats on lethality, blood cholinesterase activities, and serum cholinesterase isoenzymes.
H2-receptor antagonists inhibit cholinesterase (ChE) activity. We examined perturbations in ChE isoenzyme patterns and ChE activities of rats from the combined effects of fenthion (FEN) and cimetidine (CIM). Sixty-four female Sprague-Dawley rats were divided into 8 groups. Four rat groups were given FEN or gum arabic solution and each group divided into 2 small groups according to the CIM or gum arabic administration. FEN was administered po at 12.3 mg/kg (1/20 LD50) or 24.5 mg/kg (1/10 LD50) for 14 days or 49 mg/kg (1/5 LD50) every 4 days. CIM was given po at 1,500 mg/kg from days 7 to 13. Samples were collected 3 h after CIM administration on days 8 and 13. CIM did not influence ChE isoenzyme patterns or ChE activity. FEN inhibited both the ChE isoenzyme patterns and ChE activities without producing clinical signs. Although 1 rat in the 12.5 mg FEN/kg + CIM group died on day 10, all rats in other FEN (24.5 mg/kg or 49 mg/kg) + CIM groups died on days 8-10. Differences in suppression of ChE isoenzyme patterns were detectable between the FEN-dosed and FEN + CIM-dosed groups. There were no differences in ChE activities between the FEN-dosed and FEN + CIM-dosed groups. The i.p. administration of 500 mg CIM/kg (LD50) did not suppress ChE activities.
Sakaguchi
K
K
College of Environmental Health, Azabu University, Kanagawa, Japan.
Akahori
F
F
Shirai
M
M
Masaoka
T
T
Arishima
K
K
Kounenis
G
G
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood*; D002927:Cimetidine / Q000633:toxicity*; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005284:Fenthion / Q000633:toxicity*; D006170:Gum Arabic; D006635:Histamine H2 Antagonists / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D007527:Isoenzymes / Q000097:blood*; D007928:Lethal Dose 50; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D006635:Histamine H2 Antagonists; D007306:Insecticides; D007527:Isoenzymes; D002927:Cimetidine; D006170:Gum Arabic; D005284:Fenthion; D002802:Cholinesterases