Age-related differences in the inhibition of neuropathy target esterase and susceptibility to triphenyl phosphite-induced delayed neurotoxicity in chickens.
Triphenyl phosphite (TPP)-induced delayed neurotoxicity, which is thought to resemble but somewhat differ from classical organophosphate-induced delayed neurotoxicity (OPIDN), is known to be age-dependent. The relationship between clinical appearance and histopathological lesions, and the inhibition of neurotoxicity target esterase (NTE) in nervous tissues were compared in young and adult chickens after i.v. administration of TPP. NTE inhibition by TPP in vitro was also compared between the two age groups. Fourteen days after i.v. administration of TPP (50 mg/kg), adult chickens (24 months old) showed obvious histopathological lesions as well as obvious clinical neurological signs. On the other hand, young chickens (65 days old) showed few histopathological lesions and only marginal neurological signs. NTE activity in brain, spinal cord, and sciatic nerves was inhibited in a dose-dependent manner in both age groups. While inhibition tended to be mild in the younger chickens, the level of activity was less than 30% of the normal value in all three tissues at 24 hours after administration of 50mg/kg of TPP (14% vs. 8% in brain, 15% vs. 9% in spinal cord and 13% vs. 14% in sciatic nerves). Recovery of NTE activity in the sciatic nerves was faster in the younger chickens. The IC50 of TPP on brain (6.67 vs. 6.76 x 10(-8)M) and spinal cord NTE (1.05 vs. 1.53 x 10(-7)M) was almost the same in the two age groups. These results confirmed age-specific susceptibility to TPP, not only clinically but also histopathologically, and, suggested that the differences in both TPP metabolism and NTE recovery are related to and/or contribute to this age specificity. Judging from the age specificity and the figure of NTE inhibition, the delayed neurotoxicity produced by an i.v. administration of TPP is virtually identical to classical organophosphate-induced delayed neurotoxicity. Hydrolytic products may produce additional effects characteristic of TPP-induced neurotoxicity observed after an s.c. dose.
Katoh
K
K
Department of Public Health, Fukushima Medical College.
D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D002645:Chickens; D004950:Esterases / Q000037:antagonists & inhibitors*; D005260:Female; D009420:Nervous System / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009943:Organophosphorus Compounds / Q000633:toxicity*; D017905:Phosphites
D009943:Organophosphorus Compounds; D017905:Phosphites; C013318:triphenyl phosphite; D004950:Esterases