Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice.
OBJECTIVE
Several liver diseases that are characterized by chronic steatosis lead to steatohepatitis lesions in some susceptible subjects. We tested the hypothesis that acute or chronic steatosis may lead to lipid peroxidation.


METHODS
Diverse steatogenic treatments were administered to mice, and lipid peroxidation was assessed by measuring thiobarbituric acid reactants in the liver and the exhalation of ethane in breath.


RESULTS
Administration of ethanol (5 g/kg), tetracycline, chlortetracycline, demeclocycline (0.25 mmol/kg each), amineptine (1 mmol/kg), amiodarone (1 mmol/kg), pirprofen (2 mmol/kg), or valproate (2 mmol/kg) led to microvesicular steatosis of the liver and lipid peroxidation. After tetracycline administration, hepatic triglycerides reached a maximum at 24 h and then declined; ethane exhalation followed a similar time course. Microvesicular steatosis and lipid peroxidation were also observed after 4 days of treatment with either ethionine (0.02 mmol/kg daily) or dexamethasone (0.25 mmol/kg daily) or after 7 days of tetracycline (0.25 mmol/kg daily) administration. Administration of ethanol in the drinking water for 5.5 months led to macrovacuolar and microvesicular steatosis, lipid peroxidation, and a few necrotic hepatocytes.


CONCLUSIONS
We conclude that acute or chronic fat deposition due to a variety of compounds was associated with lipid peroxidation in mice. We suggest that the presence of oxidizable fat in the liver leads to peroxidation, and that chronic lipid peroxidation might represent the common (but not exclusive) mechanism for the possible development of steatohepatitis lesions in conditions characterized by chronic steatosis.
Unite de Recherche de Physiopathologie Hepatique, Hopital Beaujon, Clichy, France.
P
P
Letteron
B
B
Fromenty
B
B
Terris
C
C
Degott
D
D
Pessayre
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D004980:Ethane / Q000378:metabolism; D000431:Ethanol / Q000097:blood; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D013752:Tetracycline / Q000097:blood; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D000431:Ethanol; D013752:Tetracycline; D004980:Ethane