Abstract
4-Pentenoic acid (P.A.) an analog of hypoglycin, the compound that causes Jamaican vomiting sickness, was given to rats in an attempt to reproduce Reye's syndrome. Twelve rats given a single dose of 200 mg/kg of P.A. intraperitoneally developed hyperventilation, prostration and finally seizures and death. These animals had elevated ammonia (P.A.=162.4 ± 32.9 [S.E.M.] vs control [C]=44.6 ± 3.7 μg/100 ml; p <.01)and, in fasted rats, hypoglycemia (serum glucose P.A.=95.3 ± 14.6 vs C=146.9 ± 6.1 mg/100 ml; p <.01). In long-term experiments 15 rats were given 50 mg/kg of P.A. every 4 hours for 10 doses followed by a single dose of 200 mg/kg. Treated rats had enlarged livers (P.A.=7.49 ± .35 vs C=5.87 ± .16 gm; p <.001) that showed extensive small vacuole fatty degeneration, an elevated SGOT (P.A.=136.1 ± 22.6 vs C=66.4 ± 7.1 IU; p <.02), an elevated BUN (P.A.=29.7 ± 1.0 vs C=16.8 ± .8; p <-001) and normal bilirubin levels. P.A. (1mM) inhibited palmitate oxidation in rat liver slices 47 ± 10%. Evidence indicates the impairment of fatty acid oxidation results in the other metabolic abnormalities caused by P.A. The similarity in clinical and laboratory findings in this animal model, in Jamaican vomiting sickness, and in Reye's syndrome suggests that the pathophysiology, most likely secondary to impaired fatty acid oxidation, may be similar in all three. This model may prove useful for further studies of the pathophysiology and treatment of Reye's syndrome.
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Glasgow, A., Chase, H. REYE'S SYNDROME: A MODEL AND A HYPOTHESIS. Pediatr Res 8, 432 (1974). https://doi.org/10.1203/00006450-197404000-00555
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DOI: https://doi.org/10.1203/00006450-197404000-00555
