Decrease of phosphofructokinase activity in relation to the pathogenesis of triorthocresyl-phosphate-induced delayed neuropathy.
The in vivo effect of a single dose of the neuropathic compound triorthocresyl-phosphate (TOCP) on phosphofructokinase (PFC, E.C. 2.7.1.11) and its relation with the initiation step (inhibition and aging of neuropathy target esterase, NTE) in the TOCP-induced delayed neuropathy have been studied. Hens were treated with a neurotoxic dose of TOCP (500 mg/kg, p.o.) and with a protective compound (Phenylmethanesulfonyl fluoride, PMSF, 30 mg/kg s.c.) in different combinations: TOCP, TOCP + PMSF, PMSF + TOCP and PMSF. PFK activity was determined in brain and sciatic nerve 1, 3, 7 and 15 days after treatment. PFK activity decreased in sciatic nerve 15 days after dosing with TOCP or TOCP + PMSF. When animals were dosed with the protective agent (PMSF) alone or before administering the neurotoxic compound, PFK activity was unaltered and clinical signs of neuropathy were absent. The data presented here suggest that phosphofructokinase is involved in the pathogenesis of the neuropathy induced by TOCP.
Hernández
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AF
Departamento de Medicina Legal, Facultad de Medicina, Universidad de Granada, Spain.
Pla
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Villanueva
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D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001921:Brain / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000032:analysis; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002645:Chickens; D005260:Female; D008214:Lymphocytes / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000502:physiology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010732:Phosphofructokinase-1 / Q000172:deficiency* / Q000502:physiology; D012584:Sciatic Nerve / Q000201:enzymology; D013997:Time Factors; D014317:Tritolyl Phosphates / Q000037:antagonists & inhibitors / Q000633:toxicity*
D009419:Nerve Tissue Proteins; D014317:Tritolyl Phosphates; D010664:Phenylmethylsulfonyl Fluoride; D010732:Phosphofructokinase-1; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C025541:tri-o-cresyl phosphate