Paricalcitol Attenuates Bleomycin-induced Pulmonary Fibrosis: Insights from Immunohistochemical and Molecular Genetic Analysis.

Abstract

Introduction: Pulmonary fibrosis is a progressive disease marked by excessive fibrotic transformation of lung tissue. Paricalcitol, a selective vitamin D receptor (VDR) agonist, has shown promise in reducing fibrosis in experimental models, primarily due to its anti-inflammatory and anti-fibrotic properties. This study evaluates the therapeutic effects of paricalcitol on bleomycin-induced pulmonary fibrosis in a rat model.

Materials and methods: Fifty-four male Wistar rats were randomly assigned to three groups: a control group, a bleomycin-induced pulmonary fibrosis group (PF), and a bleomycin-induced pulmonary fibrosis group with paricalcitol treatment (PF+P). Pulmonary fibrosis was induced via intratracheal bleomycin instillation, and paricalcitol was administered every two days to the PF+P group. Effects were assessed through histopathological, immunohistochemical, and molecular genetic analyses, including mRNA expression levels of inflammatory and fibrotic markers at 10, 20, and 30 days.

Results: Paricalcitol treatment significantly reduced fibrosis severity, with the Aschoff score decreasing on day 30 to 2.50±0.63 compared with 5.88±0.52 in untreated PF rats (p = 0.02). The number of CD80+ M1 macrophages was reduced on day 10 (29.9±3.8 vs 64.2±5.2, p = 0.001), while CD163+ M2 macrophages were increased (30.7±2.7 vs 21.7±2.8, p = 0.03) compared to the control group. Paricalcitol also decreased TGF-β1 expression on day 30 (47.1±5.3 vs 70.8±7.1, p = 0.03) and MMP-9 on day 20 (28.9±2.5 vs 76.4±4.7, p < 0.001).

Discussion: The present study investigates the effects of paricalcitol, a selective vitamin D receptor (VDR) agonist, on bleomycin-induced pulmonary fibrosis, revealing notable reductions in inflammatory and fibrotic markers. Our findings indicate that paricalcitol treatment (PF+P group) significantly attenuates fibrosis severity, as observed through histopathological, immunohistochemical, and molecular genetic analyses.

Conclusion: Paricalcitol markedly reduces fibrosis severity, as shown through histopathological, immunohistochemical, and molecular genetic analyses. The treatment decreased the expression of key fibrotic and inflammatory markers, including TGF-β, MMP9, IL-1β, and TNF-α, and shifted macrophage polarization toward an anti-inflammatory M2 phenotype. These findings suggest paricalcitol's potential in modulating the immune response and highlight its therapeutic promise.