Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.

Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells

“…These conditions also led to an insulin resistance state, which was observed by the increased levels of fasting serum glucose and insulin, and was confirmed by HOMA-IR and QUICKI. The current results are consistent with previous studies and further support the ability of HFD to induce accumulation of fat in the liver with marked increases in insulin resistance conditions [ 23 ], which in turn increases oxidative stress in the liver causing hepatic lipid peroxidation and triggers inflammatory responses [ 24 ]. Moreover, an insulin resistance condition is usually associated with adipose tissue dysfunction and ectopic lipid deposition [ 2 , 25 ].…”

The Azadirachta indica (Neem) Seed Oil Reduced Chronic Redox-Homeostasis Imbalance in a Mice Experimental Model on Ochratoxine A-Induced Hepatotoxicity

“…In addition, the generation of secondary active forms stimulates radical development [ 19 ]. Free radical production is part of normal cellular function but increased redox-homeostatic imbalance damages all types of macromolecules [ 20 ], and produces hepatotoxicity [ 21 ], and liver fibrosis [ 22 ].…”

Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats

“…This suggests that the increase in plasma cholesterol and triglycerides in rats on the HFD compared to control rats is indicative of hepatic lipogenesis characterised by the development of NAFD, a condition that fuels the formation of acetyl CoA with consequences for the cellular redox state. NAFD could explain the hypercholesterolemia that we highlighted, that could be a consequence of hepatic insulin resistance leading to reduced synthesis of ApoB and thus VLDL [29]. In addition, our findings from imaging CT revealed a different distribution of adipose tissue in HFD rats with respect to controls.…”

“…At the same time, the liver of the HFD rat model exhibits hepatic lipid peroxidation and dysfunction [15]. High oxidative stress promotes the development of non-alcoholic fatty liver disease (NAFD), playing a key role in the progression of hepatic steatosis [29]. Such hepatic oxidative damage may also trigger extracellular matrix deposition and fibrosis in the liver, which is prevented by the supplementation of antioxidant-rich food.…”