Investigation of an Animal Model of a Reye-Like Syndrome Caused by Margosa Oil

Abstract

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.

Inhibition of Mitochondrial Functions by Margosa Oil: Possible Implications in the Pathogenesis of Reye's Syndrome

“…It is, therefore, possible for mitochondrial toxins to induce RS. It has recently been reported that MO can trigger RS in infants (I) and that it can mimic symptoms similar to those in RS in animal model in vivo (2). Therefore, we designed this study to investigate the effects of MO on some mitochondrial functions.…”

“…This oil is known to cause RS in infants (I) and can induce symptoms similar to those of RS in rats (2) …”

Mitochondria in Pathogenesis

“…Nuclei were normal, suggestive of microvesicular steatosis (Sinniah et al, 1985). The cause was determined to be severe cerebral edema, probably secondary to hyperammonemia.…”

Evaluation of Methanolic and Ethanolic Extracts of Azadirachta Indica Seed Oil for Hypoglycaemic Properties and Effects on Some Biochemical Parameters in Diabetic Mice

“…The bioactive components of the oil derived from crushing the seed has a very wide spectrum of action in medicine, and they aid in the treatment of diabetes by opposing autoimmune response, helping the beta cells to produce insulin (12). According (13), administration of the leaf extracts to laboratory rats caused decreasing of blood glucose levels. (14) also reported that leaf extracts produced an approximately 35% reduction in blood glucose levels in normal and streptozocin diabetic induced rats.…”