Abstract
The current review aimed to outline the functions of the renin angiotensin system (RAS) in the context of the oxidative stress-associated liver disease. Areas covered: Angiotensin II (Ang II) as the major effector peptide of the RAS is a pro-oxidant and fibrogenic cytokine. Mechanistically, NADPH oxidase (NOX) is a multicomponent enzyme complex that is able to generate reactive oxygen species (ROS) as a downstream signaling pathway of Ang II which is expressed in liver. Ang II has a detrimental role in the pathogenesis of chronic liver disease through possessing pro-oxidant, fibrogenic, and pro-inflammatory impact in the liver. The alternative axis (ACE2/Ang(1-7)/mas) of the RAS serves as an anti-inflammatory, antioxidant and anti-fibrotic component of the RAS. Expert commentary: In summary, the use of alternative axis inhibitors accompanying with ACE2/ Ang(1-7)/mas axis activation is a promising new strategy serving as a novel therapeutic option to prevent and treat chronic liver diseases.
Keywords:
NADPH oxidase; Renin–angiotensin system; angiotensin II; angiotensin converting enzyme inhibitor; angiotensin receptor blocker; anti-oxidant; liver disease; oxidative stress.
MeSH terms
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Angiotensin I / metabolism
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Angiotensin II / metabolism
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Angiotensin Receptor Antagonists / therapeutic use
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Angiotensin-Converting Enzyme 2
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Angiotensin-Converting Enzyme Inhibitors / therapeutic use
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Animals
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Anti-Inflammatory Agents / adverse effects
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Anti-Inflammatory Agents / therapeutic use*
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Antioxidants / adverse effects
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Antioxidants / therapeutic use*
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Enzyme Activation
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Enzyme Activators / therapeutic use
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Humans
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Liver / drug effects*
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Liver / metabolism
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Liver / physiopathology
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Liver Diseases / drug therapy*
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Liver Diseases / metabolism
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Liver Diseases / physiopathology
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Molecular Targeted Therapy
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NADPH Oxidases / metabolism
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Oxidative Stress / drug effects
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Peptide Fragments / metabolism
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Peptidyl-Dipeptidase A / metabolism
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Proto-Oncogene Mas
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Proto-Oncogene Proteins / agonists
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Proto-Oncogene Proteins / metabolism
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Reactive Oxygen Species / metabolism
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Receptors, G-Protein-Coupled / agonists
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Receptors, G-Protein-Coupled / metabolism
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Renin-Angiotensin System / drug effects*
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Signal Transduction / drug effects
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Treatment Outcome
Substances
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Angiotensin Receptor Antagonists
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Angiotensin-Converting Enzyme Inhibitors
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Anti-Inflammatory Agents
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Antioxidants
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Enzyme Activators
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Peptide Fragments
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Reactive Oxygen Species
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Receptors, G-Protein-Coupled
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Angiotensin II
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Angiotensin I
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NADPH Oxidases
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2
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angiotensin I (1-7)