Animal model of margosa oil ingestion with Reye-like syndrome. Pathogenesis of microvesicular fatty liver.
The aetiology and pathogenesis of Reye's syndrome (RS) are incompletely understood. A number of environmental toxins and biological agents, including viruses, have been postulated to cause RS, either acting alone or synergistically. Most investigations have suggested that the primary insult is in the liver mitochondria, leading to a complex biochemical catastrophe, with death from encephalopathy. Margosa oil (MO), a long-chain fatty acid compound, has been shown to cause a Reye-like syndrome with death from hepatoencephalopathy, in children in Malaysia and India. The present time-course study performed in MO-administered mice showed the development of hepatic lesions with many features of RS. MO acts rapidly, within 30 min, on the nuclei of hepatocytes inducing mitoses and binucleated cells. This is followed by mitochondrial injury, with swelling, rarefaction of matrix, loss of dense bodies, pleomorphism, and loss of ribosomes starting at 60 min. There is loss of liver glycogen, and proliferation and hypertrophy of the endoplasmic reticulum (ER), followed by the presence of lipid droplets in the hyaloplasm, and globules within dilated cisterns of the ER. Additional fatty acids from lipolysis of body adipocytes, and fat globules from intestinal MO ingestion further aggravate the liver fatty change. There is evidence of fat globule ingestion by endocytosis into hepatocytes at the level of the sinusoids. The development of microvesicular liver steatosis and glycogen depletion due to involvement of liver cell organelles occur rapidly as in RS.
Sinniah
R
R
Department of Pathology, National University of Singapore.
Sinniah
D
D
Chia
L S
LS
Baskaran
G
G
D000818:Animals; D004195:Disease Models, Animal; D005989:Glycerides / Q000633:toxicity*; D008099:Liver / Q000648:ultrastructure; D051379:Mice; D010938:Plant Oils / Q000633:toxicity*; D012202:Reye Syndrome / Q000139:chemically induced* / Q000473:pathology; D013729:Terpenes / Q000633:toxicity*
D005989:Glycerides; D010938:Plant Oils; D013729:Terpenes; C002443:neem oil