Redox Imbalance and Pulmonary Function in Bleomycin-Induced Fibrosis in C57BL/6, DBA/2, and BALB/c Mice

Abstract

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.