title: Inflammation, oxidative stress and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats.
abstract: Bisphenol A (BPA) is a key monomer in the production of plastics. It has been shown to be hepatotoxic. Inflammation and oxidative stress are closely linked with liver fibrosis, the major contributing factor to hepatic failure. Therefore, the aim of this study was to evaluate the impact of chronic exposure to BPA on the development of hepatic fibrosis in male rats and to determine the cross-talk between the hepatic cytokine network, oxidative stress and apoptosis. For this purpose, 30 male Wistar albino rats were divided into three equal groups as follows: the first group was given no treatment (normal control group); the second group was given corn oil once daily by oral gavage for 8 weeks (vehicle control group); and the third group received BPA (50 mg/kg body weight/day, p.o.) for 8 weeks. BPA administration induced liver fibrosis as reflected in an increase in serum hepatic enzymes activities, hepatic hydroxyproline content and histopathological changes particularly increased collagen fibre deposition around the portal tract. In addition, there was inflammation (as reflected in increase in interleukin-1beta 'IL-1β', decrease in interleukin-10 'IL-10' serum levels and increase in IL-1β/IL-10 ratio), oxidative stress (as reflected in increase in malondialdehyde (MDA) level, reduction in reduced glutathione (GSH) content and inhibition of catalase (CAT) activity) and apoptosis [as reflected in an increase in caspase-3 level and a decrease in numbers of B-cell lymphoma 2 (BCL2)-immunopositive hepatocytes]. Interestingly, BPA had an upregulating effect on an extracellular matrix turnover gene [as reflected in matrix metalloproteinase-9 (MMP-9)] and a downregulating effect on its inhibitor gene [as reflected in tissue inhibitor of matrix metalloproteinase-2 (TIMP-2)] expression. Thus, the mechanism by which BPA induced liver fibrosis seems to be related to stimulation of the inflammatory response, along with oxidative stress, the apoptotic pathway and activation of extracellular matrix turnover.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Sharkia Governorate, Egypt.
authors.forename: Sahar El-Sayed
authors.initials: SE
authors.lastname: Elswefy
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Sharkia Governorate, Egypt.
authors.forename: Fatma Rizk
authors.initials: FR
authors.lastname: Abdallah
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Sharkia Governorate, Egypt.
authors.forename: Hebatallah Husseini
authors.initials: HH
authors.lastname: Atteia
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Sharkia Governorate, Egypt.
authors.forename: Alaa Samir
authors.initials: AS
authors.lastname: Wahba
authors.affiliation: Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.
authors.forename: Rehab Abdallah
authors.initials: RA
authors.lastname: Hasan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004334:Drug Administration Schedule; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D005109:Extracellular Matrix / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D017208:Rats, Wistar; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D016207:Cytokines; D004785:Environmental Pollutants; D018836:Inflammation Mediators; D008315:Malondialdehyde; D020780:Matrix Metalloproteinase 9; D010636:Phenols; D019716:Tissue Inhibitor of Metalloproteinase-2; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: IL-1β/IL-10; apoptosis; liver fibrosis; matrix metalloproteinase-9; oxidative stress; tissue inhibitor of matrix metalloproteinase-2