Int. J. Mol. Sci. 2013, 14(10), 20704-20728; doi:10.3390/ijms141020704
Review

Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama 700-8558, Japan
* Author to whom correspondence should be addressed.
Received: 30 August 2013; in revised form: 18 September 2013 / Accepted: 29 September 2013 / Published: 15 October 2013
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
PDF Full-text Download PDF Full-Text [590 KB, uploaded 15 October 2013 14:04 CEST]
Abstract: Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.
Keywords: molecular hydrogen; non-alcoholic steatohepatitis; oxidative stress

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Takaki, A.; Kawai, D.; Yamamoto, K. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH). Int. J. Mol. Sci. 2013, 14, 20704-20728.

AMA Style

Takaki A, Kawai D, Yamamoto K. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH). International Journal of Molecular Sciences. 2013; 14(10):20704-20728.

Chicago/Turabian Style

Takaki, Akinobu; Kawai, Daisuke; Yamamoto, Kazuhide. 2013. "Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)." Int. J. Mol. Sci. 14, no. 10: 20704-20728.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert