Redox imbalance and pulmonary function in bleomycin-induced fibrosis in C57BL/6, DBA/2, and BALB/c mice

作者：Santos Silva M A; Pires K M P; Trajano E T L; Martins V; Nesi R T; Benjamin C F; Caetano M S; Sternberg C; MacHado M N; Zin W A; Valenca S S; Porto L C^*

来源：Toxicologic Pathology, 2012, 40(5): 731-741.

DOI：10.1177/0192623312441404

• mouse strains
• pulmonary fibrosis
• pulmonary function
• redox imbalance

The development of bleomycin-induced pulmonary fibrosis (BLEO-PF) has been associated with differences in genetic background and oxidative stress status. The authors'; aim was to investigate the crosstalk between the redox profile, lung histology, and respiratory function in BLEO-PF in C57BL/6, DBA/2, and BALB/c mice. BLEO-PF was induced with a single intratracheal dose of bleomycin (0.1 U/mouse). Twenty-one days after bleomycin administration, the mortality rate was over 50 in C57BL/6 and 20 in DBA/2 mice, and BLEO-PF was not observed in BALB/c. There was an increase in lung static elastance (p <.001), viscoelastic/inhomogeneous pressure (p <.05), total pressure drop after flow interruption (p <.01), and ΔE (p <.05) in C57BL/6 mice. The septa volume increased in C57BL/6 (p <.05) and DBA/2 (p <.001). The levels of IFN-γ were reduced in C57BL/6 mice (p <.01). OH-proline levels were increased in C57BL/6 and DBA/2 mice (p <.05). SOD activity and expression were reduced in C57BL/6 and DBA/2 mice (p <.001 and p <.001, respectively), whereas catalase was reduced in all strains 21 days following bleomycin administration compared with the saline groups (C57BL/6: p <.05; DBA/2: p <.01; BALB/c: p <.01). GPx activity and GPx1/2 expression decreased in C57BL/6 (p <.001). The authors conclude that BLEO-PF resistance may also be related to the activity and expression of SOD in BALB/c mice.