Production of the Features of Reye's Syndrome in Rats with 4-Pentenoic Acid

Glasgow, Allen M.; Chase, H. Peter

doi:10.1203/00006450-197503000-00005

Cited by 102 publications

(30 citation statements)

References 14 publications

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“…But there is an increasing number of reports about acute hepatic disease, presenting as Reye syndrome, in association with the use of VPA-Na [3,6,11,12,13]. VPA-Na (2nd-propylpentaenoic acid Na) shows a structural similarity to 4-pentenoic acid, which is known to induce the characteristic features of Reye syndrome in an animal model [4]. 4-pentenoic acid acts as a potent inhibitor of fatty acid oxidation [2].…”

Section: Introductionmentioning

confidence: 99%

Decreased serum carnitine in valproate induced Reye syndrome

et al. 1982

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A 3-year-old girl developed acute liver disease after treatment with valproate for 6 months. She developed the typical features of Reye syndrome. Serum free carnitine was decreased as well as 3-keto-valproic acid, the main metabolite of beta-oxidation of valproate. The serum valproate concentration was at the upper limit of the therapeutic range. The possible importance of carnitine in the pathogenesis of valproate induced liver disease is discussed.

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Section: Introductionmentioning

confidence: 99%

Decreased serum carnitine in valproate induced Reye syndrome

et al. 1982

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“…However, from the neurological point of view, only minimal, nonprogressive changes or, alternatively, collapse and death have been reported. In some instances, the infusion of glucose reversed or prevented these neurological abnormalities (7). Such features are in contrast to the progression of the encephalopathy of Reye syndrome through four (14) or five (3) distinguishable levels of deepening coma that cannot be reversed by the infusion of glucose alone.…”

mentioning

confidence: 56%

“…The latter could well be due to the brevity of **Arcinue, E. L., Reye's III Symposium, Nov. [6][7]1980. Detroit, MI (abstr.…”

Section: Discussionmentioning

confidence: 99%

Development of encephalopathic features similar to Reye syndrome in rabbits.

Kang¹,

Olson²,

Jabbour³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The progression of neurological abnormalities through four or five clinically distinguishable levels of deepening coma and the development of a fatty liver are the hallmarks of Reye syndrome. A number of animal models have been described that result in fatty liver formation with minimal, static, or catastrophic neurological changes. In this study, we attempted to produce neurological features in rabbits that reflected a rostral-caudal progression of abnormalities that could be categorized into clinically distinguishable levels reminiscent of Reye syndrome. This was accomplished by the intracisternal administration of 0.5-25 mg of 11,14-icosadienoic acid (20:2wo6) suspended in a mixture of rabbit serum and isotonic saline solution. A reproducible, dose-titratable spectrum of at least four levels of deepening coma could be produced at will. Increases in serum glutamate-oxaloacetate transaminase and creatine kinase and changes in serum glucose resulted 1-2 hr after the neurological abnormalities were evoked. Other unsaturated fatty acids produced similar responses. Those tested included 18:1w9, 18:2w6, 18:3a3, 20:3w6, 20:4o6, and 22:4w6 fatty acids. Saturated fatty acids, including 6:0, 8:0, 16:0, 18:0, and 20:0, failed to elicit these effects. The abnormalities were sustained for 30-120 min after a single dose. Full recovery was observed in some animals that had not reached the fourth level of our grading system for coma. Pretreatment of the rabbits with aspirin modulated the neurological abnormalities. Twenty micrograms of bee venom melittin, which activates endogenous phospholipase A2, administered intracisternally into rabbits also produced signs of level 3 (our grading system) coma for several hours. These findings suggest a possible role for polyunsaturated fatty acids in the development of Reye syndrome and offer a means of producing the neurological components of that syndrome in a laboratory animal.Reye syndrome is a rare but clinically important childhood encephalopathy of unknown origin associated with fatty visceral changes and complex metabolic abnormalities (1, 2). The encephalopathy is a progressive one with four or five stages "each correlating with progressive rostral-caudal central nervous system involvement" as first recognized by Several animal models have been proposed, including the use of a specific inhibitor of fatty acid oxidation (7), the infusion of those metabolites that are found in increased concentrations in the blood of affected patients (8, 9), and the inoculation of animals with viruses, either alone or in conjunction with special diets or prior exposure of the animals to chemicals (10-13). Fatty liver formation and biochemical evidence of liver dysfunction have been observed in each of these models. However, from the neurological point of view, only minimal, nonprogressive changes or, alternatively, collapse and death have been reported. In some instances, the infusion of glucose reversed or prevented these neurological abnormalities (7). Such features are in contrast to t...

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“…The authors suggest that it is unlikely that exposure to pentenoic acid or related compounds causes Reye's syndrome, but rather the two conditions share similar biochemical defects. One effect of pentenoic acid is to block fatty acid oxidation (5). Although specific short-chain fatty acid concentrations have not been measured after pentenoic acid injection, it is possible that this block in fatty acid oxidation leads to accumulation of fatty acids such as octanoate, which in turn produce the clinicopathologic syndrome observed in the rats.…”

Section: Discussionmentioning

confidence: 99%

“…Several other animal models for Reye's syndrome have been proposed (2)(3)(4)(5). The One most closely related to the octanoate model is produced by injection of 4-pentenoic acid into rats (5).…”

Section: Discussionmentioning

confidence: 99%

Pathologic Changes in a Rabbit Model of Reye's Syndrome

Trauner

1982

Pediatr Res

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Production of the Features of Reye's Syndrome in Rats with 4-Pentenoic Acid

Cited by 102 publications

References 14 publications

Decreased serum carnitine in valproate induced Reye syndrome

Decreased serum carnitine in valproate induced Reye syndrome

Development of encephalopathic features similar to Reye syndrome in rabbits.

Pathologic Changes in a Rabbit Model of Reye's Syndrome

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