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Titolo:
TRIPHENYLPHOSPHITE NEUROPATHY IN HENS
Autore:
FIORONI F; MORETTO A; LOTTI M;
Indirizzi:
UNIV PADUA,IST MED LAVORO,VIA FACCIOLATI 71 I-35127 PADUA ITALY UNIV PADUA,IST MED LAVORO I-35127 PADUA ITALY
Titolo Testata:
Archives of toxicology
fascicolo: 10, volume: 69, anno: 1995,
pagine: 705 - 711
SICI:
0340-5761(1995)69:10<705:TNIH>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED DELAYED NEUROTOXICITY; PHENYLMETHANESULFONYL FLUORIDE; TARGET ESTERASE; PHENYLMETHYLSULFONYL FLUORIDE; PHOSPHITE NEUROTOXICITY; NERVOUS-SYSTEM; POLYNEUROPATHY; PATHOGENESIS; INVIVO; TOCP;
Keywords:
ORGANOPHOSPHATE DELAYED POLYNEUROPATHY; HENS; NEUROPATHY TARGET ESTERASE; PROMOTION; PROTECTION; TRIPHENYL PHOSPHITE; RETROGRADE AXONAL TRANSPORT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
F. Fioroni et al., "TRIPHENYLPHOSPHITE NEUROPATHY IN HENS", Archives of toxicology, 69(10), 1995, pp. 705-711

Abstract

Single doses of triphenyl phosphite (TPP), a triester of trivalent phosphorus, cause ataxia and paralysis in hens. Characteristics of neurotoxicity were described as somewhat different from organophosphate induced delayed polyneuropathy (OPIDP), which is caused by triesters of pentavalent phosphorus. The onset of TPP neuropathy was reported to occur earlier than that of OPIDP (5-10 versus 7-14 days after dosing, respectively), and chromatolysis, neuronal necrosis and lesions in certain areas of the brain were found in TPP neuropathy only. Pretreatment with phenylmethanesulfonyl fluoride (PMSF) protects from OPIDP, but it either partially protected from effects of low doses or exacerbated those of higher doses of TPP. In order to account for these differences with OPIDP, it was suggested that TPP neuropathy results from the combination of two independent mechanisms of toxicity: typical OPIDP due to inhibition of neuropathy target esterase (NTE) plus a second neurotoxicity related with other target(s). We explored TPP neuropathy in thehen with attention to the phenomena of promotion and protection whichare both caused by PMSF when given in combination with typical neuropathic OPs. When PMSF is given before neuropathic OPs it protects from OPIDP; when given afterwards it exaggerates OPIDP. The former effect is due to interactions with NTE, the latter to interactions with an unknown site. The time course of NTE reappearance after TPP (60 or 90 mg/kg i.v.) inhibition showed a longer half-life when compared to that after PMSF (30 mg/kg s.c. ) (10-15 versus 4-6 days, respectively). The clinical signs of TPP neuropathy (60 or 90 mg/kg i.v.) were similar to those observed in OPIDP, appeared 7-12 days after treatment, correlatedwith more than 70% NTE inhibition/aging and were preceded by a reduction of retrograde axonal transport in sciatic nerve of hens. TPP (60 mg/kg i.v.) neuropathy was promoted by PMSF (120 mg/kg s.c.) given up to 12 days afterwards and was partially protected by PMSF (10-120 mg/kgs.c.) when given 24 h before TPP (60 or 90 mg/kg i.v.). The previously reported early onset of TPP neuropathy might be related to the higher dose used in those experiments and to the resulting more severe neuropathy. The lack of full protection might be explained by the slow kinetics of TPP, which would cause substantial NTE inhibition when PMSF effects on NTE had subsided. Since PMSF also affects the promotion sitewhen given before initiation of neuropathy, the resulting neuropathy would then be due to both protection from and promotion of TPP effectsby PMSF. No promotion by PMSF (120 mg/kg s.c.) was observed in TPP neuropathy (90 mg/kg i.v.) partially protected by PMSF (10-30 mg/kg s.c.). This might also be explained by the concurrent effects on NTE and on the promotion site obtained with PMSF pretreatment. We conclude thatTPP neuropathy in the hen is likely to be the same as typical OPIDP. The unusual effects of combined treatment to hens with TPP and PMSF are explained by the prolonged pharmacokinetics of TPP and by the dual effect of PMSF i.e. protection from and promotion of OPIDP.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 16:23:20