Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease

Abstract

Liver steatosis without alcohol consumption, namely, nonalcoholic fatty liver disease (NAFLD), is a common hepatic condition that encompasses a wide spectrum of presentations, ranging from simple accumulation of triglycerides in the hepatocytes without any liver damage to inflammation, necrosis, ballooning, and fibrosis (namely, nonalcoholic steatohepatitis) up to severe liver disease and eventually cirrhosis and/or hepatocellular carcinoma. The pathophysiology of fatty liver and its progression is influenced by multiple factors (environmental and genetics), in a “multiple parallel-hit model,” in which oxidative stress plays a very likely primary role as the starting point of the hepatic and extrahepatic damage. The aim of this review is to give a comprehensive insight on the present researches and findings on the role of oxidative stress mechanisms in the pathogenesis and pathophysiology of NAFLD. With this aim, we evaluated the available data in basic science and clinical studies in this field, reviewing the most recent works published on this topic.

Docosahexaenoic acid and hydroxytyrosol co‐administration fully prevents liver steatosis and related parameters in mice subjected to high‐fat diet: A molecular approach

“…The latter finding is principally associated with the abolishment of HFD‐induced activation of the redox‐sensitive factor NF‐κB, as a consequence of the normalization of the oxidative status of the liver, in addition to the increased availability of resolvins avoiding inflammatory development. Collectively, these findings point toward oxidative stress as an important acting factor in the development in HFD‐dependent liver steatosis and establishment of a pro‐inflammatory state, which can further increase in NASH to progress into fibrosis and cirrhosis . Hence, abrogation of hepatic steatosis by combined DHA and HT would represent a crucial therapeutic strategy eluding disease progression into stages lacking efficacious handling at present time …”

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

“…The overproduced reactive oxygen species (ROS) will make the antioxidant system incapable of clearing and oxidative stress. Meanwhile, abnormal oxidation of fat deposition is aggravated by the massively generated peroxidation, resulting in more serious lipid degeneration (Masarone et al, ; Spahis et al, ; Videla, Rodrigo, Araya, & Poniachik, ). In addition, previous studies have shown that the level of ROS was elevated in T2DM mice, in which the antioxidant capacity was reduced (Lu et al, ; Lu et al, ; Lu et al, ; X. Zhu, Cheng, et al, ).…”

Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

“…Mitochondrial β‐oxidation breaks down FFAs but produces ROS, which causes liver damage. FFAs also induce endoplasmic reticulum (ER) stress, which is caused by accumulation of unfolded and misfolded proteins, and ER stress is another potent source of ROS . Melatonin has strong antioxidant effects and can be utilized to protect the liver from NAFLD or fatty acid‐induced liver damage.…”