title: Phenylmethanesulfonyl fluoride delays the recovery from crush of peripheral nerves in hens.
abstract: Several esterase inhibitors (carbamates, phosphinates and sulfonyl halides) have been shown to promote organophosphate-induced delayed polyneuropathy (OPIDP). The mechanism of promotion is not understood, but indirect evidence suggests impairments of peripheral nerve repair. Also, other toxic neuropathies, such as those caused by 2,5-hexanedione in hens and bromophenylacetylurea in rats, have been reported to be promoted by phenylmethanesulfonyl fluoride (PMSF). Hen sciatic nerve was crushed at the bifurcation. Either mild or heavy pressure was applied by forceps obtaining a mild and rapidly recovering lesion (possibly myelinic) or a more severe, long-lasting lesion (possibly axonal), respectively. Hens were then treated with PMSF (120 mg/kg s.c. or 200 mg/kg s.c. x 2, 24 h apart) either before (5-48 h) crush or afterwards (5-48 h). Controls received vehicle only. Animals were observed for reappearance of digit movements, and standing and walking ability. PMSF treatment did not change the clinical outcome when animals received a mild crush. In hens receiving the more severe crush the reappearance of digit movements and the complete clinical recovery were observed after 43 +/- 14 and 63 +/- 9 days, respectively. In animals treated with PMSF there was a significant delay in both reappearance of digit movements (56 +/- 11 days when PMSF was given 24 and 48 h before crush, and 55 +/- 10 days, when given 24 and 48 h after crush) and in clinical recovery (75 +/- 15 and 80 +/- 18 days, respectively). It is concluded that traumatic axonopathy as well as toxic neuropathies can be promoted by PMSF. Moreover, it appears that PMSF promotion involves a target and a mechanism which are present in healthy axons and do not need to be activated by the insult to the axon.
authors.affiliation: Istituto di Medicina del Lavoro, Università di Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Moretto
authors.forename: E
authors.initials: E
authors.lastname: Capodicasa
authors.forename: M
authors.initials: M
authors.lastname: Peraica
authors.forename: M
authors.initials: M
authors.lastname: Lotti
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D002645:Chickens; D005260:Female; D009409:Nerve Crush; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D010664:Phenylmethylsulfonyl Fluoride / Q000633:toxicity*
chemical_list: D010664:Phenylmethylsulfonyl Fluoride