Acute hepatic failure with swollen mitochondria and microvesicular fatty degeneration of hepatocytes triggered by free radical initiator.
BACKGROUND
Reye syndrome and acute fatty liver of pregnancy are characterized by acute hepatic failure associated with characteristic pathologic changes of hepatocytes, i.e., microvesicular fatty degeneration with severe mitochondrial swelling. Several animal models of these conditions have been proposed, although none has demonstrated sufficiently similar laboratory and pathologic features.


METHODS
A single dose of 2,2'-azobis-(2-amidinopropane) dihydrochloride, a free radical initiator, 100 mg/kg of body weight, injected intraperitoneally to BALB/c mice induced a transient decrease in hepatic energy charge, liver mitochondrial respiratory activity, and succinate dehydrogenase activity and a transient increase in blood ammonia level, suggesting hepatic failure.


RESULTS
The hepatocytes displayed microvesicular fatty degeneration with severely swollen mitochondria.


CONCLUSIONS
This is the first model of acute hepatic failure with microvesicular fatty degeneration of hepatocytes. It suggests a role of free radicals in the pathogenesis of certain types of acute hepatic failure.
Saibara
T
T
First Department of Medicine, Kochi Medical School, Nankoku, Japan.
Himeno
H
H
Ueda
H
H
Onishi
S
S
Yamamoto
Y
Y
Enzan
H
H
Hara
H
H
Takehara
Y
Y
Utsumi
K
K
D000227:Adenine Nucleotides / Q000378:metabolism; D000578:Amidines; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005609:Free Radicals; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008933:Mitochondrial Swelling; D014280:Triglycerides / Q000378:metabolism
D000227:Adenine Nucleotides; D000578:Amidines; D005609:Free Radicals; D014280:Triglycerides; C046728:2,2'-azobis(2-amidinopropane); D002784:Cholesterol