title: Metformin administration induces hepatotoxic effects in paraoxonase-1-deficient mice.
abstract: Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin reduces body weight and decreases the risk of diabetes-related complications such as cardiovascular disease. However, whether metformin elicits beneficial effects on liver histology is a controversial issue and, as yet, there is no consensus. Paraoxonase-1 (PON1), an enzyme synthesized mainly by the liver, degrades lipid peroxides and reduces oxidative stress. PON1 activities are decreased in chronic liver diseases. We evaluated the effects of metformin in the liver of PON1-deficient mice which, untreated, present a mild degree of liver steatosis. Metformin administration aggravated inflammation in animals given a standard mouse chow and in those fed a high-fat diet. Also, it was associated with a higher degree of steatosis in animals fed a standard chow diet. This report is a cautionary note regarding the prescription of metformin for the treatment of diabetes in patients with concomitant liver impairment.
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: García-Heredia
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Riera-Borrull
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain; Laboratori de Referència Sud, Hospital Universitari de Sant Joan, Reus, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fort-Gallifa
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Fedra
authors.initials: F
authors.lastname: Luciano-Mateo
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Cabré
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Hernández-Aguilera
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.affiliation: Unitat de Recerca Biomèdica (CRB-URB), Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain. Electronic address: jcamps@grupsagessa.com.
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000172:deficiency*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D008054:Lipid Peroxides; D008687:Metformin; D043303:Aryldialkylphosphatase
keywords: Antioxidants; Hepatotoxicity; Inflammation; Metformin; NAFLD; Paraoxonase; Steatosis