title: The effect of Z-FA.FMK on D-galactosamine/TNF-alpha-induced liver injury in mice.
abstract: Cathepsin B is a cysteine proteinase, considered to have an important role in apoptosis, which is activated by D-galactosamine and tumor necrosis factor-alpha (D-GalN/TNF-alpha). Benzyloxycarbonyl-L-phenylalanine fluoromethyl ketone (Z-FA.FMK) is a cathepsin B inhibitor used in research on apoptotic pathways. The aim of this study was to investigate the role of Z-FA.FMK on apoptotic cell death, cell proliferation and liver damage induced by a D-GalN/TNF-alpha combination in mice. In the study, 1 h after administration of 8 mg/kg Z-FA.FMK by intravenous injection, D-GalN (700 mg/kg) and TNF-alpha (15 microg/kg) were administered by a single intraperitoneal injection. In the group given D-GalN/TNF-alpha, the following results were found: Degenerative changes in the liver tissue, significant increase in the number of both TUNEL and activated caspase-3-positive hepatocytes, a decrease in the number of PCNA-positive hepatocytes, an increase in lipid peroxidation (LPO) levels and a decrease in glutathione (GSH) and DNA levels in the liver tissue. In contrast, in the group given D-GalN/TNF-alpha and Z-FA.FMK, a decrease in the damage of the liver tissue, a significant decrease in TUNEL and activated caspase-3-positive hepatocytes, a significant increase in the number of PCNA-positive hepatocytes, a decrease in the LPO levels, an increase in GSH and DNA levels in the liver tissue were found. As a result, microscopic and biochemical evaluations indicate that Z-FA.FMK plays a protective role against liver injury induced by D-GalN/TNF-alpha and it has an inverse effect on hepatocyte apoptosis and proliferation in BALB/c mice.
authors.affiliation: Department of Biology, Science Faculty, University of Istanbul, Vezneciler, Istanbul, Türkiye. selgez@istanbul.edu.tr
authors.forename: S
authors.initials: S
authors.lastname: Gezginci
authors.forename: S
authors.initials: S
authors.lastname: Bolkent
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004151:Dipeptides / Q000008:administration & dosage*; D005688:Galactosamine; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007659:Ketones / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha
chemical_list: D004151:Dipeptides; D007659:Ketones; D014409:Tumor Necrosis Factor-alpha; C057383:MDL 201053; D005688:Galactosamine