Evaluation of renal damage in a bleomycin-induced murine model of systemic sclerosis

Objective(s): Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology with a high mortality rate. Renal crisis has been reported as one of the predictors of early mortality in these patients. The present study was performed to evaluate bleomycin-induced SSc using an osmotic minipump as a possible model for the analysis of renal damage in SSc.Materials and Methods: Male CD۱ mice were implanted with osmotic minipumps loaded with saline or bleomycin and sacrificed at ۶ and ۱۴ days. Histopathological analysis was performed through hematoxylin and eosin (H&E) and Masson’s trichrome staining. The expression of endothelin ۱ (ET-۱), inducible nitric oxide synthase (iNOS), transforming growth factor β (TGF-β), and ۸-hydroxy-۲-deoxyguanosine (۸-OHdG) was also evaluated by immunohistochemistry.Results: The administration of bleomycin induced a decrease in the length of Bowman’s space (۳.۶ μm, P<۰.۰۰۱); an increase in collagen deposition (۱۴.۶%, P<۰.۰۰۰۱); and an increase in the expression of ET-۱ (۷.۵%, P<۰.۰۰۰۱), iNOS (۱۰.۸%, P<۰.۰۰۰۱), ۸-OHdG (۱۶۱ nuclei, P<۰.۰۰۰۱), and TGF-β (۲.۴% µm, P<۰.۰۰۰۱) on Day ۶. On Day ۱۴, a decrease in the length of Bowman’s space (۲.۶ μm, P<۰.۰۰۰۱); increased collagen deposition (۱۳.۴%, P<۰.۰۰۰۱); and increased expression of ET-۱ (۲.۷%, P<۰.۰۰۱), iNOS (۱۰.۱%, P<۰.۰۰۰۱), ۸-OHdG (۱۳۳ nuclei, P<۰.۰۰۱), and TGF-β (۰.۶%, P<۰.۰۰۰۱) were also observed.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.

کلیدواژه ها:

Bleomycin ، Fibrosis ، Kidney ، Oxidative stress ، Systemic sclerosis ، Scleroderma ، Scleroderma renal crisis