Abstract

Aim: Animal species and strains exhibit varying degrees of sensitivity to bleomycin-induced dermal fibrosis. This study aimed to establish early (week 2) and late (week 4) changes in bleomycin-induced skin fibrosis in two species (mice and rats) and three strains (BALB/C mice, C57BL/6 mice, Wistar rats) using histopathological and radiological analyses.

Materials and Methods

Female C57BL/6 and BALB/C mice (n=4 each, 20-25 g, six weeks old) and female Wistar rats (n=4, 200-250 g, six weeks old) were subjected to subcutaneous bleomycin (10 mg/kg/day) or phosphate-buffered saline (PBS) every other day for four weeks. Skin biopsies from the four dorsal quadrants were analyzed for collagen homogenization, eosinophil and basophil counts, inflammatory response, and histological skin thickness (from 3 sections and ten different high-power fields in each biopsy).

Results: The collagen homogenization score, eosinophil density, mast cell density, inflammatory response score, and skin thickness were higher in the bleomycin group than in the PBS group across all models. Collagen scores were similar across models, but the inflammatory response and eosinophil and mast cell densities were higher at week 2 than at week 4. The highest inflammatory response scores at week 2 were observed in the BALB/C and Wistar mice. Histological skin thickness was greatest in Wistar rats at weeks 2 and 4.

Conclusion: The early inflammatory response was more severe in the BALB/C and Wistar models, although all models showed comparable collagen density and skin thickness. Wistar rats exhibited the most consistent parameters, making them suitable models for bleomycin-induced dermal fibrosis.