Table 1.

A summary of the main studies that associated oxidative stress with liver diseases.

Type of Study	Model	Observed Effects	Ref.
In vivo	Acute and chronic ethanol administration	ROS participates in the pathological processes of fatty liver and fibrosis development	[25,26]
Clinical	Alcohol abuse	Elevated oxidative markers	[27,28,29]
Ex vivo	Elevated alcohol consumption	Protein adducts	[30]
In vitro	Stimulated neutrophils	ROS increases production of procollagen mRNA	[31]
In vitro	HSC and primary hepatocytes pyrazole-treated rats	Changes in collagen protein by ROS-dependent mechanisms	[32]
In vivo	Mice deficient in NOX	Exhibited attenuated ROS production	[33]
In vivo	NO inhibition	Increased collagen deposition and liver damage	[34]
In vitro	HSC incubated with ONOO−	NO plays no role during the late phase of fibrogenesis	[35]
In vivo	iNOS deficiency in CCl4-induced fibrosis	Decreased collagen synthesis; inhibited ONOO− formation and HSC apoptosis	[36]
In vivo	Endotoxemia	Nitrosative stress.	[37]
In vitro	Peroxynitrite donor	Peroxynitrite may contribute to the activation of pro-MMP-2	[38]
In vivo	Blockade of iNOS	Induced antifibrotic effects	[39]
In vivo	Lacking KEAP1	Minor susceptibility to hepatic injury	[40]
In vivo	NRF2-null mice stimulated with ethanol	Developed macrovascular steatosis and fulminant liver injury	[41,42,43,44]
In vitro	Tert-butylhydroquinone	Stimulated HSC activation and increased fibrogenic gene expression	[43]
In vivo	Deletion of NRF2	Rapid onset and progression of nutritional steatohepatitis in mice	[45]
Ex vivo and in vitro	Human fibrotic liver and transient transfections of NRF2 via plasmids	Correlation between Nrf2 in HSCs and development of hepatic fibrosis NRF2 induced lipocyte phenotype in HSCs	[46]
In vitro and in vivo	Monosodium urate crystals, CCl4, and TAA	Inflammasome-mediated regulation of hepatic stellate cells	[47]
In vitro and in vivo	Monosodium urate crystals, H202 and NLRP3 activators, and Txnip–/– mice	TXNIP deficiency impaired activation of the NLRP3 inflammasome and subsequent secretion of interleukin 1β	[48]

ROS, reactive oxygen species; HSC, hepatic stellate cell.