Following reports of a
Reye-like syndrome in children resulting from
Margosa oil (MO) ingestion, we administered MO to laboratory rats in an attempt to produce an animal model of
Reye's syndrome. Male rats were injected intraperitoneally with either MO or
corn oil and observed for clinical signs of a toxic response. After 15 h the animals were administered a second dose and the MO-treated animals developed florid neurological symptoms. The animals were then sacrificed and blood samples were analyzed for
glucose,
ammonia,
aspartate aminotransferase, and
alanine aminotransferase. Sections of liver, kidney, and brain were examined by light microscopy after
Sudan black B,
hematoxylin and
eosin, and
periodic acid-Schiff staining. Liver was additionally examined by electron microscopy. Liver samples were analyzed for hepatic
enzyme levels and brain samples were analyzed for water content. There were greatly increased levels of
ammonia,
aspartate aminotransferase, and
alanine aminotransferase and decreased
glucose levels in the blood of MO-treated animals. Light microscopy of MO-treated livers revealed fatty infiltration, granularity of the cytoplasm with normal nuclei, and
glycogen depletion; electron microscopy revealed mitochondrial pathology in the livers of MO-treated animals. There were no significant morphological changes in brain or kidney specimens although the kidneys did show some fatty infiltration. Hepatic mitochondrial
enzyme levels were unchanged and there was no increase in brain water content in the MO-treated animals. Thus, many of the abnormalities seen in
Reye's syndrome were seen in this model; however, there were no hepatic
enzyme changes despite altered mitochondrial morphology and no evidence of
cerebral edema despite a florid
encephalopathy. Nonetheless, this model may have important implications for the understanding of the pathogenetic mechanisms of this
Reye-like syndrome and, perhaps,
Reye's syndrome.