Oxidative stress in experimental liver microvesicular steatosis: role of mitochondria and peroxisomes.
BACKGROUND
Hepatic microvesicular steatosis is a clinical manifestation seen in a number of liver diseases. Although the role of mitochondrial beta-oxidation in the development of the disease has been well studied, information on lipid peroxidative damage in liver subcellular organelles is scarce. The present study looked at oxidative stress in hepatic peroxisomes and microsomes in microvesicular steatosis, using an animal model of the disease.


METHODS
Rats were given i.p. injections of sodium valproate (700 mg/kg bodyweight) to induce microvesicular steatosis, which was confirmed by histology.


RESULTS
Oxidative stress was evident in liver in steatosis, accompanied by structural and functional alterations in hepatic mitochondria. Alterations in lipid composition, with decreased phosphatidyl choline and ethanolamine and increased lysophosphatidyl choline and ethanolamine, were seen. An increase in triglyceride content was also seen. In addition, increased lipid peroxidation was also evident in peroxisomes and microsomes from steatotic rats. Pretreatment with clofibrate results in partial reversal of changes produced by valproate.


CONCLUSIONS
These results suggest that in addition to impaired mitochondrial beta-oxidation, oxidative stress is also seen in the hepatic peroxisomes and microsomes during microvesicular steatosis.
Natarajan
Sathish Kumar
SK
Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Eapen
Chundamannil E
CE
Pullimood
Anna B
AB
Balasubramanian
Kunissery A
KA
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D002994:Clofibrate / Q000008:administration & dosage; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008930:Mitochondria, Liver / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D020675:Peroxisomes / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D010743:Phospholipids; D014635:Valproic Acid; D002994:Clofibrate