Neurotoxicity of Fatty Acid Anilides in Rabbits

Rodrigo, José; Robles, Mercedes; Mayo, I.; Pestaña, Ángel; Marquet, Anne; Larraga, Vicente; Munoz, Erik

doi:10.1016/s0140-6736(83)91527-1

Cited by 15 publications

(5 citation statements)

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“…Rodrigo et al reported that repeated doses of anilides to rabbits induced ataxia and paralysis, and the vacuolation of the white matter of the cerebellum and spinal cords, necrosis of Purkinje's cells in the cerebellum, as well as muscular degeneration and eosinophilic interstitial pneumonitis [24]. Autoimmune toxicity or eosinophil related allergic response has been suggested as the mechanisms of the neurotoxicity [24]. However, no inflammatory responses were found in either nervous tissues nor skeletal muscles in this study, and the number of white blood cells was within the normal range in rats treated with aniline (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Okazaki

Yamashita

Sudo

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. The neurotoxicity of aniline and its age-dependent responses were investigated in male rats. Groups of 6 rats, 4-week-old, were treated once with aniline (500, 750 or 1,000 mg/kg) or olive oil by gavage. Additional groups of 6 rats, 7-or 10-week-old, were treated once with 800 mg/kg of aniline or olive oil. Paralytic gait or hindlimb paralysis was observed between post-treatment days 8 and 15 in two out of six rats receiving 1,000 mg/kg of aniline at 4 weeks of age. On post-treatment day 15, spongy change in the white matter of the spinal cord was observed in all rats receiving 750 or 1,000 mg/kg of aniline at 4 weeks of age. The lateral and ventral columns of the thoracic spinal cord were the most severely affected. Spongy change in the facial nerve and spinal trigeminal tracts of pons and medulla oblongata, and mild degeneration of the peripheral nerves was found in 3 out of 6 rats receiving 1,000 mg/kg of aniline. At the ultrastructural level, the spongy change was due to distention of the myelin sheath and splitting of the intraperiod line. Axons were well preserved in the affected nerve fibers. No abnormalities were seen in the neuronal cell bodies. Although transient cyanosis was observed in all rats receiving 800 mg/kg of aniline at 7-or 10-week-old, as well as in rats receiving 750 or 1,000 mg/kg of aniline at 4-week-old, no treatment-related neurobehavioral or morphologic abnormalities were found in the former. These findings demonstrate the neurotoxicity of orally administered aniline for rats, depending upon the age of the animal at the time of administration. KEY WORDS: aniline, hindlimb paralysis, neurotoxicity, rat, spongy change with myelin vacuolation.

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Section: Discussionmentioning

confidence: 99%

“…The anilides, aniline-derivatives, also induced paralysis and vacuolation of the white matter of the cerebellum and spinal cord in rabbits [24]. However, the influence of aniline itself to the nervous system has not been fully examined in animals.…”

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confidence: 99%

Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Okazaki

Yamashita

Sudo

et al. 2001

The Journal of Veterinary Medical Science

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“…The severity of lesions has been also decreased in recovering animals [ 114 ]. In another study, vacuolation of the spinal cord and cerebellum in the white matter, paralysis, ataxia, necrosis of Purkinje’s cells, as well as eosinophilic interstitial pneumonitis and muscular degeneration also observed in rabbits after exposure to anilides and aniline-derivatives [ 115 ]. The mechanisms of the neurotoxicity were shown to be related to eosinophil related allergic response or autoimmune toxicity [ 115 ].…”

Section: Neurotoxicity Of Anilinementioning

confidence: 99%

“…In another study, vacuolation of the spinal cord and cerebellum in the white matter, paralysis, ataxia, necrosis of Purkinje’s cells, as well as eosinophilic interstitial pneumonitis and muscular degeneration also observed in rabbits after exposure to anilides and aniline-derivatives [ 115 ]. The mechanisms of the neurotoxicity were shown to be related to eosinophil related allergic response or autoimmune toxicity [ 115 ]. However, the results showed no inflammatory responses in either skeletal muscles or nervous tissues in this study, and the normal range of white blood cells number was detected in rats after treatment with aniline.…”

Section: Neurotoxicity Of Anilinementioning

confidence: 99%

Molecular Mechanism of Aniline Induced Spleen Toxicity and Neuron Toxicity in Experimental Rat Exposure: A Review

Makhdoumi

Hossini

Ashraf

et al. 2019

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Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors formation at the end. However, the molecular mechanism(s) of aniline-induced spleen toxicity is not understood well, previous studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and DNA subsequently, in the spleen.. Elevated expression of cyclins, cyclin-dependent kinases (CDKs) and phosphorylation of pRB protein along with increases in A, B and CDK1 as a cell cycle regulatory proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cell cycle regulation, which contributes to tumorigenic response after aniline exposure. Aniline-induced splenic toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expression (OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions in rat. Oxidative stress causes transcriptional up-regulation of fibrogenic/inflammatory factors (cytokines, IL-1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redox-sensitive transcription factors, in aniline treated-rats. The upstream signalling events as phosphorylation of IκB kinases (IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) could potentially be the causes of activation of NF-κB and AP-1. All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. The spleen toxicity of aniline is studied more and the different mechanisms are suggested. This review summarizes those events following aniline exposure that induce spleen toxicity and neurotoxicity.

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“…Neurotoxic effects of anilides have been reported in rabbits (Rodrigo et al 1983) although no other suitable animal model for the toxic syndrome has been found. In particular, administration of anilides and of oils containing anilides to rats, mice, and hamsters in this and other laboratories have failed to produce a toxic response (Beaubernard et al 1982;Aldridge and Connors 1983).…”

Section: Introductionmentioning

confidence: 99%

Hydrolysis of oleylanilide in the rat

1983

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The fate of oleylanilide, administered as a single intragastric dose in rape oil, has been studied in Porton Wistar rats. Following a dose of oleyl[U-14C]anilide approximately 60% of the label was recovered in the faeces over a 3 day period, and identified principally as unchanged anilide. Most of the remainder of the dose was recovered in urine as hydrophilic metabolites. p-hydroxyacetanilide, which is a major metabolite of aniline in the rat was identified in the hydrolysed samples of urine from anilide treated rats. Following administration of [9,10(n)-3H]oleyl[U-14C]-anilide to rats which had been fitted with a cannula in the thoracic lymph duct the [3H] label which was absorbed was recovered principally in triglycerides showing that extensive hydrolysis of the anilide occurs prior to or during uptake from the gut. Oleylanilide was identified in lymph by gas chromatography but amounted to less than 6% of the dose.

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Neurotoxicity of Fatty Acid Anilides in Rabbits

Cited by 15 publications

References 0 publications

Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Molecular Mechanism of Aniline Induced Spleen Toxicity and Neuron Toxicity in Experimental Rat Exposure: A Review

Hydrolysis of oleylanilide in the rat

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