Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease

Masarone, Mario; Rosato, Valerio; Dallio, Marcello; Gravina, Antonietta Gerarda; Aglitti, Andrea; Loguercio, Carmelina; Federico, Alessandro; Persico, Marcello

doi:10.1155/2018/9547613

Cited by 514 publications

(437 citation statements)

References 117 publications

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“…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 …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Attenuation of high‐fat diet (HFD)‐induced liver steatosis is accomplished by different nutritional interventions. Considering that the n‐3 PUFA docosahexaenoic acid (DHA) modulates lipid metabolism and the antioxidant hydroxytyrosol (HT) diminishes oxidative stress underlying fatty liver, it is hypothesized that HFD‐induced steatosis is suppressed by DHA and HT co‐administration. Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg/kg/day), HT (5 mg/kg/day) or both. The combined DHA + HT protocol fully prevented liver steatosis and the concomitant pro‐inflammatory state induced by HFD, with suppression of lipogenic and oxidative stress signaling, recovery of fatty acid oxidation capacity and enhancement in resolvin availability affording higher inflammation resolution capability. Abrogation of HFD‐induced hepatic steatosis by DHA and HT co‐administration represents a crucial therapeutic strategy eluding disease progression into stages lacking efficacious handling at present time.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…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, ).…”

Section: Discussionmentioning

confidence: 99%

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

Yang

Cai

et al. 2019

Phytotherapy Research

170

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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.

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“…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.…”

Section: Functional Roles and Therapeutic Potentials Of Melatonin Andmentioning

confidence: 99%

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

Sato

Meng

Francis

et al. 2020

Journal of Pineal Research

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Circadian rhythms and clock gene expressions are regulated by the suprachiasmatic nucleus in the hypothalamus, and melatonin is produced in the pineal gland. Although the brain detects the light through retinas and regulates rhythms and melatonin secretion throughout the body, the liver has independent circadian rhythms and expressions as well as melatonin production. Previous studies indicate the association between circadian rhythms with various liver diseases, and disruption of rhythms or clock gene expression may promote liver steatosis, inflammation, or cancer development. It is well known that melatonin has strong antioxidant effects. Alcohol drinking or excess fatty acid accumulation produces reactive oxygen species and oxidative stress in the liver leading to liver injuries. Melatonin administration protects these oxidative stress‐induced liver damage and improves liver conditions. Recent studies have demonstrated that melatonin administration is not limited to antioxidant effects and it has various other effects contributing to the management of liver conditions. Accumulating evidence suggests that restoring circadian rhythms or expressions as well as melatonin supplementation may be promising therapeutic strategies for liver diseases. This review summarizes recent findings for the functional roles and therapeutic potentials of circadian rhythms and melatonin in liver diseases.

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Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease

Cited by 514 publications

References 117 publications

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

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

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

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

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