Rosiglitazone, a peroxisome proliferator activated receptor (PPAR)-γ agonist and originally developed as an anti-diabetic agent, have been known to have a protective effect against alcoholic toxicity in patients with non-alcoholic fatty liver. To inv...
Rosiglitazone, a peroxisome proliferator activated receptor (PPAR)-γ agonist and originally developed as an anti-diabetic agent, have been known to have a protective effect against alcoholic toxicity in patients with non-alcoholic fatty liver. To investigate the underlying mechanisms of this protective effects of rosiglitazone, several in vitro experiments including the measurement of cell viability, mitochondrial aldehyde dehydrogenase (ALD2) expression, anti-oxidant enzymes activities, the mitochondrial apoptotic cascades and in vivo experiments including histopathologic examinations of liver by hematoxylin & eosin and TUNEL staining and blood chemistry were performed. We found that ALD2 and anti-oxidant enzymes expressions were inhibited in HepG2 cells under hyperlipidemic condition, and rosiglitazone reversed the expression of these genes. Sole acetaldehyde and acetaldehyde-free fatty acids (FFAs) impaired both ALD2 and anti-oxidant enzymes expressions. However, these conditions were reversed by rosiglitazone treatment indicating that rosiglitazone may regulate ALD2 and anti-oxidant enzymes in HepG2 cells. It also prevented apoptotic cascades including Bax and Bcl-2 ratio, cytochrome c release, and caspase-3 activation. In in vivo experiment, we found that high fat diet and alcohol-induced aspartate aminotransferase, alanine aminotransferase, triglycerides, free fatty acids, and total bilirubin were significantly decreased and hepatic apoptosis was prevented by rosiglitazone treatment. Finally, we propose that rosiglitazone treatment may provide therapeutic strategy for the prevention of alcohol toxicity in non-alcoholic fatty liver via recovery of ALD2 and anti-oxidant enzymes.