Nonalcoholic fatty liver disease (NAFLD) represents a broad spectrum of
histological abnormalities with clinical presentations ranging from hepatic steatosis to
nonalcoholic steatohepatitis (NASH). Some NAFLD patients may progress to cirrhosis
and ultimately hepatocellular carcinoma (HCC). Hepatic steatosis, the hallmark of
NAFLD, is defined by the accumulation of triglycerides (TGs) in more than 5% of the
hepatocytes. NASH is characterized by inflammation along with variable degrees of fibrosis in addition to steatosis.
NAFLD has been considered to be the hepatic manifestation of metabolic syndrome (MS), as it is frequently associated
with MS conditions such as insulin resistance (IR) and obesity. Hepatic steatosis mainly results from disrupted homeostasis
of lipid metabolism in the setting of IR. Although the mechanism underlying the progression from steatosis to NASH
is still not fully elucidated, mounting evidence has suggested oxidative stress (OS) to be a key driving force. Elevated OS
has been well documented in NAFLD patients. OS can cause direct damages to lipid, protein, and DNA molecules and
trigger the inflammatory and fibrogenesis signaling pathways, which promotes the progression from steatosis to NASH.
OS may also have various effects on antioxidant defense mechanisms. Overproduced reactive oxygen species (ROS) may
directly deplete antioxidant molecules such as glutathione (GSH) and inhibit the activities of antioxidant enzymes such as
superoxide dismutase (SOD). ROS may also induce the expression of antioxidant genes to counteract the OS effects. The
aim of this review is to discuss oxidative stress and antioxidant mechanisms in NAFLD.
Keywords: Antioxidant, alcohol metabolism, fatty acid oxidation, lipid metabolism, NAFLD, NASH, oxidative stress, reactive
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