Cathepsin B inhibition improves lung injury associated to D-galactosamine/tumor necrosis factor-alpha-induced liver injury in mice.


Oztay F. , Gezginci-Oktayoglu S. , Bayrak B. B. , Yanardag R. , Bolkent S.

Molecular and cellular biochemistry, vol.333, pp.65-72, 2010 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 333
  • Publication Date: 2010
  • Doi Number: 10.1007/s11010-009-0205-3
  • Journal Name: Molecular and cellular biochemistry
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.65-72
  • Keywords: Cathepsin B, D-GalN/TNF-alpha, Lung injury, Oxidative stress, TRAF-1, HEPATOCYTE APOPTOSIS, TNF-ALPHA, EPITHELIAL-CELLS, FACTOR RECEPTOR, NITRIC-OXIDE, LIPOPOLYSACCHARIDE, EXPRESSION, MODULATION, ACTIVATION, RESISTANT

Abstract

The present study was designed to investigate the effects of benzyloxicarbonyl-l-phenylalanyl-alanine-fluoromethylketone (Z-FA.FMK), an inhibitor of cathepsin B on lung injury that occurs concurrently with liver injury induced by d-galactosamine/tumor necrosis factor-alpha (d-GalN/TNF-alpha). Four groups of BALB/c male mice were treated as follows: Group 1-mice receiving intravenous (iv) injections of physiological saline; Group 2-administered with 8 mg/kg Z-FA.FMK by iv injection; Group 3-mice treated with 700 mg/kg d-GalN and 15 mu g/kg TNF-alpha by sequential intraperitoneal (ip) injection; Group 4-treated with 700 mg/kg d-GalN and 15 mu g/kg TNF-alpha by sequential ip injection 1 h after administration with 8 mg/kg Z-FA.FMK. Mice from Groups 3 and 4 were sacrificed 4 h after d-GalN/TNF-alpha injections. The mice treated with d-GalN/TNF-alpha showed lung damage; increased TNF receptor-associated factor immunoreactivity, lipid peroxidation, protein carbonyl content, and lactate dehydrogenase activity; decreased catalase, superoxide dismutase, and paraoxonase activities. Treatment with Z-FA.FMK resulted in an improvement of these alterations in d-GalN/TNF-alpha-administered mice. The apoptotic index of type-II pneumocytes was the almost same in the four study groups, but pneumocytes labeled with proliferating cell nuclear antigen antibody was more numerous in Group 4 mice. Our results show that d-GalN/TNF-alpha results in lung damage without induction of apoptosis. Treatment with Z-FA.FMK stimulates proliferation of type-II pneumocytes and improves degenerative alterations in injured lung occurred with liver injury induced by d-GalN/TNF-alpha.