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Comparative evolution of mipafox-induced delayed neuropathy in rats and hens
1Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061.
Abstract:
Adult male Long-Evans rats and White Leghorn hens were given 30 mg/kg mipafox ip. Administration of this organophosphorus ester resulted in > or = 89% inhibition of brain and spinal cord neurotoxic esterase activity in both species 4 hr after dosing. Our sequential, comparative study of the bilateral mipafox-induced neuropathy in the medulla and cervical spinal cord in hens and rats demonstrated that the rats had well-developed, vacuolar axonopathic lesions in the fasciculus gracilis by post-dosing day 7. Severely affected rats with such lesions were noted through day 21, but not subsequently (days 28 and 35). The hen had a slower developing, but more severe, consistent and longer lasting neuropathy than the rat. In these birds, lesions in the medulla and rostral cervical spinal cord levels were more extensive, involving large regions of both the spinocerebellar tracts and fasciculus gracilis. Neuropathic changes, including myelinated fiber axonopathy and Wallerian-like degeneration, were prominent from days 14 - 35 in hens, and were associated with prominent gliosis in the later stages.
Insights
Organophosphorus ester mipafox caused neurotoxicity in rats and hens. Hens developed a more severe and persistent neuropathy than rats, showing significant axonopathic lesions.
Area of Science:
- Neuroscience
- Toxicology
- Veterinary Medicine
Background:
- Organophosphorus esters are known neurotoxicants.
- Neurotoxic esterase (NTE) is a key enzyme in neuronal function.
- Understanding species-specific responses to neurotoxins is crucial for risk assessment.
Purpose of the Study:
- To comparatively investigate the neuropathological effects of mipafox in rats and hens.
- To characterize the temporal development and severity of mipafox-induced neuropathy in two species.
Main Methods:
- Adult male Long-Evans rats and White Leghorn hens were administered 30 mg/kg mipafox.
- Brain and spinal cord neurotoxic esterase (NTE) activity was assessed.
- Neuropathological examination of the medulla and cervical spinal cord was performed at various time points post-dosing.
Main Results:
- Mipafox induced significant NTE inhibition (>89%) in both species within 4 hours.
- Rats exhibited vacuolar axonopathic lesions in the fasciculus gracilis by day 7, resolving by day 21.
- Hens displayed a slower-onset, more severe, and prolonged neuropathy with extensive lesions in multiple tracts, persisting through day 35.
Conclusions:
- Hens are more susceptible to mipafox-induced neuropathy than rats, exhibiting greater severity and duration.
- The study highlights species-specific differences in the neuropathological response to organophosphorus esters.
- Findings contribute to understanding the mechanisms of organophosphate-induced neurotoxicity and interspecies variability.