Conclusion
Systemic administration of bleomycin via an osmotic minipump produces histopathological changes in the kidneys, similar to kidney damage in SSc. Therefore, this model would allow the study of molecular alterations associated with SSc-related renal damage.
Methods
Male CD1 mice were implanted with osmotic minipumps loaded with saline or bleomycin and sacrificed at 6 and 14 days. Histopathological analysis was performed through hematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of endothelin 1 (ET-1), inducible nitric oxide synthase (iNOS), transforming growth factor β (TGF-β), and 8-hydroxy-2-deoxyguanosine (8-OHdG) was also evaluated by immunohistochemistry.
Results
The administration of bleomycin induced a decrease in the length of Bowman's space (3.6 μm, P<0.001); an increase in collagen deposition (14.6%, P<0.0001); and an increase in the expression of ET-1 (7.5%, P<0.0001), iNOS (10.8%, P<0.0001), 8-OHdG (161 nuclei, P<0.0001), and TGF-β (2.4% µm, P<0.0001) on Day 6. On Day 14, a decrease in the length of Bowman's space (2.6 μm, P<0.0001); increased collagen deposition (13.4%, P<0.0001); and increased expression of ET-1 (2.7%, P<0.001), iNOS (10.1%, P<0.0001), 8-OHdG (133 nuclei, P<0.001), and TGF-β (0.6%, P<0.0001) were also observed.