The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.
The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.
Veronesi
B
B
Padilla
S
S
Lyerly
D
D
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D007531:Isoflurophate / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology; D013118:Spinal Cord Diseases / Q000139:chemically induced* / Q000473:pathology
D007531:Isoflurophate; C005238:mipafox; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase