title: Oxidant stress is a significant feature of primary biliary cirrhosis.
abstract: Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P<0.001; plasma malondialdehyde (MDA), P=0.007] compared to age- and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P=0.013) and serum selenium and vitamin A were also lower (both P<0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of early-stage PBC.
authors.affiliation: The Liver Unit, Department of Gastroenterology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Aboutwerat
authors.forename: Philip W
authors.initials: PW
authors.lastname: Pemberton
authors.forename: Alexander
authors.initials: A
authors.lastname: Smith
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burrows
authors.forename: Raymond F T
authors.initials: RF
authors.lastname: McMahon
authors.forename: Sanjiv K
authors.initials: SK
authors.lastname: Jain
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Warnes
mesh_terms: D000975:Antioxidants / Q000032:analysis; D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002779:Cholestasis / Q000473:pathology; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000097:blood / Q000652:urine; D005978:Glutathione / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008315:Malondialdehyde / Q000097:blood; D016877:Oxidants / Q000097:blood / Q000652:urine; D018384:Oxidative Stress; D012643:Selenium / Q000097:blood; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D016877:Oxidants; D014801:Vitamin A; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D015237:Dinoprost; D005978:Glutathione; D012643:Selenium; D001205:Ascorbic Acid