Mitochondrial Abnormality and Oxidative Stress in Nonalcoholic Steatohepatitis
Article first published online: 27 FEB 2007
Alcoholism: Clinical and Experimental Research
Volume 31, Issue Supplement s1, pages S61–S66, January 2007
How to Cite
Kojima, H., Sakurai, S., Uemura, M., Fukui, H., Morimoto, H. and Tamagawa, Y. (2007), Mitochondrial Abnormality and Oxidative Stress in Nonalcoholic Steatohepatitis. Alcoholism: Clinical and Experimental Research, 31: S61–S66. doi: 10.1111/j.1530-0277.2006.00288.x
- Issue published online: 27 FEB 2007
- Article first published online: 27 FEB 2007
- Received for publication August 24, 2005; accepted October 17, 2005.
- Nonalcoholic Steatohepatitis;
- Oxidative Stress;
- Reactive Oxygen Species;
- Mitochondrial Abnormality
Background: Oxidative stress plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Mitochondrial abnormality may be associated with the onset and progression of NASH via excessive formation of mitochondrial reactive oxygen species. This study aimed to investigate the role of mitochondrial abnormality in NASH in relation to oxidative stress.
Methods: Twenty-six patients with NASH, 11 with simple steatosis, and 10 healthy volunteers underwent clinico-pathological analysis. The liver/spleen ratio, an index of the hepatic fat content, was evaluated with computed tomography. Plasma glutathione levels were measured as an antioxidative marker, and the urinary 8-isoprostane levels and 3-nitrotyrosine staining in the liver as an oxidative stress marker. Mitochondrial abnormality was estimated by serum levels of mitochondria aspartate transaminase (mAST) and the mitochondrial staining in the liver.
Results: Urinary 8-isoprostane levels were higher in NASH than in the healthy volunteers, whereas plasma glutathione levels were similar in the 2 groups. In NASH, urinary 8-isoprostane levels positively correlated with alanine transaminase levels and negatively with the liver/spleen ratio. The 3-nitrotyrosine staining was more advanced in simple steatosis and NASH than in the normal liver, but was similar in simple steatosis and NASH. In contrast to the normal mAST levels in the healthy volunteers and simple steatosis, serum mAST levels were elevated in one-fourth of the NASH patients and positively correlated with urinary 8-isoprostane levels in NASH. Most cases of NASH showed diffuse or focal but intense mitochondrial staining in the liver in contrast to scattered staining in simple steatosis.
Conclusions: Our present study demonstrated that in NASH, the enhanced oxidative stress may be associated with hepatic inflammation and the degree of fat infiltration in the liver. However, simple steatosis and NASH were both exposed to oxidative stress, while NASH alone was associated with mitochondrial abnormality. These findings indicate that mitochondrial abnormality may play a role in the onset and progression of NASH in correlation with oxidative stress.