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- Title
Rosiglitazone Protects Against Alcohol Toxicity In Non-Alcoholic Fatty Liver.
- Authors
Tae Woo Jung; Ji Young Lee; Eun Mi Park; Se Eun Park; Jae Hyuk Lee; Eun Seok Kang; Chul Woo Ahn; Hyun Chul Lee; Bong Soo Cha
- Abstract
Rosiglitazone, a peroxisome proliferator activated receptor (PPAR)-γagonist 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, antioxidant 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 by 72 and 40% compared with control 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 (81 and 51% compared with control) and anti-oxidant enzymes (50 and 30% compared with control) 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.
- Subjects
HYPOGLYCEMIC agents; TOXICOLOGY of alcohol; FATTY liver; ALDEHYDE dehydrogenase; ANTIOXIDANTS
- Publication
Diabetes, 2007, Vol 56, pA680
- ISSN
0012-1797
- Publication type
Article