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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
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Int. J. Mol. Sci. 2013, 14(10), 20704-20728; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141020704
Received: 30 August 2013 / Revised: 18 September 2013 / Accepted: 29 September 2013 / Published: 15 October 2013
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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. View Full-Text
Keywords: molecular hydrogen; non-alcoholic steatohepatitis; oxidative stress molecular hydrogen; non-alcoholic steatohepatitis; oxidative stress
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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. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141020704

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. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141020704

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. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141020704

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