Neuropathologic Effects of Phenylmethylsulfonyl Fluoride (PMSF)-Induced Promotion and Protection inn Organophosphorus Ester-Induced Delayed Neuropathy(Opidn) in Hens

The serine/cysteine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) has been used both to promote and to protect against neuropathic events of organophosphorus-induced delayed neuropathy (OPIDN) in hens (Lotti et al., 1991; Veronesi et al., 1985; Pope and Padilla, 1990; Pope et al., 1993). This study expands upon this work by correlating clinical and neuropathological findings in these modifications of OPIDN. To provide appropriate models of OPIDN, single phenyl saligenin phosphate (PSP) dosages of 0.5, 1.0, or 2.5 mg/kg were administered to adult hens. PMSF (90 mg/kg) was given either 4 hours after or 12 hours prior to PSP administration. Clinical signs and pathologic changes in the biventer cervicis nerve (El-Fawal et al., 1988) were monitored. PSP alone, 2.5 mg/kg, ellicitated severe OPIDN (terminal clinical score 7.5 & ± 1.0 [0-8 scale]; neuropathology score 2.7 ± 0.3 [0-4 scale, based on myelinated fiber degeneration]). PMSF given 12 hours prior to PSP gave complete protection (clinical and neuropathology scores of 0; p<0.0001). Signs and lesions of OPIDN were absent following 0.5 mg/kg PSP alone, but PMSF given 4 hours after PSP potentiated its neurotoxic effects (clinical score 4.0 ± 0.0; neuropathology score 3.5 ± 0.3; p<0.0001). At the time of sacrifice, there was a correlation (r = 0.61) between the clinical score on the last day of observation and the neuropathology scores (p<0.0001). This study demonstrates that the intensity of peripheral nerve myelinated fiber degeneration correlates with clinical deficits in PMSF-induced potentiation and protection in OPIDN.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Small Animal Clinical Sciences

Department dc:contributor.department

Small Animal Clinical Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2000

Author dc:creator

• Massicotte, Christiane II

Chair dc:contributor.committeechair

• Jortner, Bernard S.

Committee members dc:contributor.committeemember

• Ehrich, Marion F.
• Inzana, Karen D.
• Jortner, Bernard S.

• Toxicology
• Organophosphate
• Neuropathy
• Promotion

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-3798-154753

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/10100