Relationship between cholinesterase inhibition and thermoregulation following exposure to diisopropyl fluorophosphate in the rat.
This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents.
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Fogelson
L
L
Richards
J
J
Highfill
J
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D007279:Injections, Subcutaneous; D007531:Isoflurophate / Q000633:toxicity*; D008297:Male; D051381:Rats; D012881:Skin Temperature / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; D002802:Cholinesterases