title: Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention.
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.
authors.affiliation: a Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|b Biotechnology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|c Pharmacology and Toxicology Department, School of Pharmacy , Tabriz University of Medical Sciences , Tabriz , Iran.|d Students Research Committee , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Ahmadian
authors.affiliation: e Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , ON , Canada.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pennefather
authors.affiliation: a Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|d Students Research Committee , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Aziz
authors.initials: A
authors.lastname: Eftekhari
authors.affiliation: f Pharmaceutical Sciences Research Center , Shiraz University of Medical Sciences , Shiraz , Iran.|g Gerash School of Paramedical Sciences , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Heidari
authors.affiliation: a Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|b Biotechnology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|c Pharmacology and Toxicology Department, School of Pharmacy , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Eghbal
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000627:therapeutic use; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D020536:Enzyme Activators; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: NADPH oxidase; Renin–angiotensin system; angiotensin II; angiotensin converting enzyme inhibitor; angiotensin receptor blocker; anti-oxidant; liver disease; oxidative stress