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. 2023;26(7):760-767.
doi: 10.22038/IJBMS.2023.67117.14720.

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

Dulce Carolina Pérez-Figueroa  1 , Edilburga Reyes-Jiménez  1 , Juan Manuel Velázquez-Enríquez  1 , Itayetzi Reyes-Avendaño  1 , Karina González-García  1 , Saúl Villa-Treviño  2 , Honorio Torres-Aguilar  3 , Rafael Baltiérrez-Hoyos  1   4 , Verónica Rocío Vásquez-Garzón  1   4
Affiliations

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

Dulce Carolina Pérez-Figueroa et al. Iran J Basic Med Sci. 2023.

Abstract

Objectives: 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 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.

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.

Keywords: Bleomycin; Fibrosis; Kidney; Oxidative stress; Scleroderma; Scleroderma renal crisis; Systemic sclerosis.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Histological staining of kidney tissue sections from control and BLM-treated mice
Figure 2
Figure 2
Immunohistochemical analysis of the renal damage marker ET-1
Figure 3
Figure 3
Immunohistochemical analysis of iNOS
Figure 4
Figure 4
Immunohistochemical analysis of the DNA damage marker 8-OHdG
Figure 5
Figure 5
Immunohistochemical analysis of the profibrotic marker TGF-β
Figure 6
Figure 6
Use of Masson's trichrome staining to assess collagen deposition
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