The Progression and Recovery of Neurotoxicity Induced by A Single Oral Dose of Aniline in Rats.

Okazaki, Yoshimasa; Yamashita, Kotaro; Sudo, Masato; Tsuchitani, Minoru; Narama, Isao; Yamaguchi, Ryoji; Tateyama, Susumu

doi:10.1293/tox.14.19

Cited by 7 publications

(14 citation statements)

References 15 publications

(16 reference statements)

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“…The physiopathology of the separation of myelin layers is not known (Van der Lugt & Venter 2007). However, some authors report that oligodendrocyte death may play a role in the separation of myelin after administration of aniline in mice (Okazaki et al 2001).…”

Section: Ultrastructural Studymentioning

confidence: 99%

Accidental and experimental Closantel intoxication in Uruguayan sheep

et al. 2015

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An outbreak of Closantel intoxication in sheep in Uruguay is described. The outbreak occurred in a group of 1300 weaning lambs treated orally with a 10% solution of Closantel. One hundred forty eight lambs showed clinical signs of intoxication and 14 died. The clinical signs included mydriasis, nystagmus, and negative pupillary reflex, bilateral blindness, bump into objects, and lateral movement of the head. No macroscopic lesions were observed. The histological lesions of the retina were cytoplasmic vacuolization in ganglion cells and in cells of the inner and outer nuclear layers with different degrees of atrophy. Vacuolization and axonal degeneration were observed in the optic nerve, with multifocal areas of fibrosis and infiltration by lymphocytes and Gitter cells. To reproduce the intoxication, four sheep were given two, four and 10 times the therapeutic dose of Closantel (0.1g/kg of BW). Only the animals receiving 10 times the recommended dose showed clinical signs. The histological examination of the lesions in experimental sheep showed similar results to those described in the accidental outbreak, except for the absence of optic nerve fibrosis and inflammation, characterizing an acute phase. Axonal myelin sheaths loss, fibroblasts and collagen fibers were observed in the ultrastructural study of the optic nerve of accidental intoxicated animals. The optic nerve of experimentally intoxicated animals had vacuoles that separated the myelin sheaths of axons. To prevent outbreaks it is suggested to weigh the animals before Closantel administration to avoid errors in dose calculation.

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Section: Ultrastructural Studymentioning

confidence: 99%

Accidental and experimental Closantel intoxication in Uruguayan sheep

et al. 2015

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“…These changes were considered to be the early stage of the spongy change induced by aniline. Although the nature of MA in the cytoplasm of the oligodendroglia is unknown, MA is observed in the cases of abnormal utilization of lipid components Okazaki et al 2001b). It is also observed in the cytoplasm of the oligodendroglia in black tremor hamsters (Kim et al 2003) and quaking mice (Watanabe and Bingle 1972) with impaired myelinogenesis in the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Activity of 2′, 3′-Cyclic Nucleotide 3′-Phosphodiesterase (CNPase) in Spinal Cord with Spongy Change Induced by a Single Oral Dose of Aniline in Rats

et al. 2010

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A spongy change in the spinal cord white matter was observed in four-week-old rats treated with aniline. Although this change was found to be a result of the myelin sheath splitting at the ultrastructural level, the mechanism is unknown. This study was conducted to identify the mechanism of the spongy change in aniline-treated rats. The spongy change in the spinal cord white matter was first detected on day 5 in the histopathologic examination. The incidence and severity of the lesions, especially in the lateral and ventral funiculi of the thoracic spinal cord white matter, increased prominently from day 8 to day 10. In all rats, immunohistochemical staining by anti-2 0 , 3 0 -cyclic nucleotide 3 0 -phosphodiesterase (CNPase) occurred along the cytoplasmic boundaries of the normal oligodendroglia. However, mild to moderate anti-CNPase staining extended to the swollen cytoplasm of the oligodendroglia in the aniline-treated rats from day 2 to day 4. In the electron microscopic examination, free ribosomes and rough endoplasmic reticula in the cytoplasm of the oligodendroglia increased on days 3 and 4. These changes were considered to be related to CNPase expression. However, CNPase expression decreased, whereas the spongy changes were detected from day 5. The reduction in CNPase expression may contribute to the changes in the myelin morphology observed in aniline intoxication.

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“…10,16 However, the role of methaemoglobinaemia in this neurotoxicity remains to be established, and there was no damage to neuronal cells in any rats receiving 4-haloanilines or in any rats receiving aniline. 17,18 Further study is required to define the relation between methaemoglobinaemia and neurotoxicity, or to determine the mechanism by which a bolus of 4-haloaniline or aniline induces neurotoxicity in rats.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies we demonstrated that a bolus dose of aniline induced neuro-toxicity in rats. 17,18 The affected rats showed hindlimb paralysis, resulting from a spongy change in the white matter of the spinal cord. Such results bear out the possibility of neurotoxicity of aniline derivatives, including halogenated anilines.…”

Section: Introductionmentioning

confidence: 99%

Potential of neurotoxicity after a single oral dose of 4‐bromo‐, 4‐chloro‐, 4‐fluoro‐ or 4‐iodoaniline in rats

Okazaki

Yamashita

Ishii

et al. 2003

J of Applied Toxicology

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The potential for neurotoxicity after a single oral dose of four halogenated aniline derivatives--4-bromoaniline (4-BA), 4-chloroaniline (4-CA), 4- fluoroaniline (4-FA) and 4-iodoaniline (4-IA)--was given to rats was investigated at or near the lethal dosage level. Hindlimb paralysis was found in the 4-BA, 4-CA and 4-FA groups on clinical observation, with the maximum incidence of 100% in the 4-BA and 4-FA groups and 66.7% in the 4-CA group. Detailed clinical observations with functional tests identified the following effects: reduced response of hindlimb extensor thrust, gait abnormality in the open field and decreased grip strength in the fore- or hindlimbs in the 4-BA, 4-CA and 4-FA groups; decreased number of supported rearing episodes in the open field in the 4-BA and 4-CA groups; abnormal landing in the aerial righting reflex in the 4-BA and 4-FA groups; and prolonged surface righting reflex in the 4-BA group. Spongy change in the white matter of the spinal cord and brainstem and nerve fibre degeneration in the peripheral nerves were found in all haloaniline-treated groups. The central and peripheral nervous systems were most severely affected in the 4-BA group and the lesions in the 4-IA group were limited in grade. This study demonstrates that a bolus dose of 4-haloanilines to rats induces a neurotoxicity similar in character to that evoked by the parent aniline. The decreasing order of neurotoxic potential appears to be 4-BA >> 4-FA > or = 4-CA >> 4-IA when comparing at or near the lethal dosage level.

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The Progression and Recovery of Neurotoxicity Induced by A Single Oral Dose of Aniline in Rats.

Cited by 7 publications

References 15 publications

Accidental and experimental Closantel intoxication in Uruguayan sheep

Accidental and experimental Closantel intoxication in Uruguayan sheep

Activity of 2′, 3′-Cyclic Nucleotide 3′-Phosphodiesterase (CNPase) in Spinal Cord with Spongy Change Induced by a Single Oral Dose of Aniline in Rats

Potential of neurotoxicity after a single oral dose of 4‐bromo‐, 4‐chloro‐, 4‐fluoro‐ or 4‐iodoaniline in rats

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