Role of Oxidative Stress in Hepatic and Extrahepatic Dysfunctions during Nonalcoholic Fatty Liver Disease (NAFLD)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a pathology that contains a broad liver dysfunctions spectrum. These alterations span from noninflammatory isolated steatosis until nonalcoholic steatohepatitis (NASH), a more aggressive form of the disease characterized by steatosis, inflammatory status, and varying liver degrees fibrosis. NAFLD is the most prevalent chronic liver disease worldwide. The causes of NAFLD are diverse and include genetic and environmental factors. The presence of NASH is strongly associated with cirrhosis development and hepatocellular carcinoma, two conditions that require liver transplantation. The liver alterations during NAFLD are well described. Interestingly, this pathological condition also affects other critical tissues and organs, such as skeletal muscle and even the cardiovascular, renal, and nervous systems. Oxidative stress (OS) is a harmful state present in several chronic diseases, such as NAFLD. The purpose of this review is to describe hepatic and extrahepatic dysfunctions in NAFLD. We will also review the influence of OS on the physiopathological events that affect the critical function of the liver and peripheral tissues.

Influence of cardiometabolic comorbidities on myocardial function, infarction, and cardioprotection: Role of cardiac redox signaling

“…Oxidative stress plays a central role for NASH and NAFLD disease progression (including cardiovascular complications) [354,355] and NOX-derived ROS represent key players in liver fibrosis [356]. Patients with NASH have higher levels of 8isoprostanes and sNox2-dp correlating with the histological grading of steatosis as well as liver inflammation, ballooning and fibrosis [357].…”

Redox‐Dependent Effects in the Physiopathological Role of Bile Acids

“…Oxidative stress is established by a disturbance between ROS and antioxidants that results in excessive oxidant milieu, leading to cellular injury [ 97 ]. Oxidative stress damages cell structures by modifying proteins, lipids, nucleotides, and membranes, affecting their functions and limiting cell viability [ 102 , 104 ]. To characterize and quantify oxidative stress, the ROS levels and antioxidant activity are typically determined.…”

Electromagnetic Fields Ameliorate Insulin Resistance and Hepatic Steatosis by Modulating Redox Homeostasis and SREBP-1c Expression in db/db Mice

“… 5 , 6 Oxidative stress can reduce insulin sensitivity and increase hepatic triglyceride (TG) content. 7 , 8 Hepatic insulin resistance can result in hepatic steatosis by causing lipid metabolism disorders, which further lead to systemic IR. 9 Excessive hepatic lipid accumulation further exacerbates IR.…”

“… 5 Thus, re-establishing systemic redox homeostasis plays an important role in treating NAFLD. 8 Unfortunately, intervention in redox systems remains a clinical challenge because of side effects that negatively impact adherence to treatment. 10 Re-establishing redox homeostasis requires new methods.…”