Testing the Possible Protective Effect of Ivermectin on Bleomycin-Induced Pulmonary Fibrosis in Albino Rats: Histological and Immunohistochemical Study

Abstract

Background and Objectives: Pulmonary fibrosis (PF) is an interstitial lung disease that leads to death and is characterized by excessive collagen deposition and tissue scarring. Bleomycin (BLM) is widely used to induce PF in rodent models, closely resembling human idiopathic pulmonary fibrosis. Ivermectin, a broad-spectrum antiparasitic agent, has recently attracted interest due to its reported anti-inflammatory and antifibrotic effects. The beneficial effects of ivermectin to treat PF may be attributed to suppressing the NLRP3 inflammasome. Ivermectin can cause acute toxicity, including convulsions, when overdosed in animals. In humans, it may induce neurological disorders, particularly in individuals with mutations in the ABCB1 gene. This study aimed to investigate the potential protective role of ivermectin against BLM-induced PF in rats. Materials and Methods: Forty adult male albino rats were randomly allocated into four groups (n = 10 each): control, ivermectin-treated (0.6 mg/kg, orally on days 0, 1, 7, and 8), BLM-treated (single intratracheal dose of 5 mg/kg), and BLM- and ivermectin-treated. Lung tissues were collected for histopathological analysis and Mallory trichrome staining to assess collagen deposition. Mast cell (MC) infiltration was assessed using toluidine blue. Immunohistochemistry for α-SMA and Ki-67 was used to evaluate myofibroblast and cell proliferation. Oxidative stress parameters, including serum total antioxidant capacity, lung glutathione and lung nitric oxide were measured. Results: Ivermectin treatment markedly attenuated BLM-induced lung fibrosis, showing reduced collagen accumulation, restoration of alveolar architecture, and decreased inflammatory cell infiltration. Immunohistochemical evaluation revealed decreased expression of α-SMA and Ki-67, while biochemical analyses demonstrated improved oxidative stress markers. Conclusions: Ivermectin significantly mitigates BLM-induced pulmonary fibrosis in rats through modulation of inflammation, suppression of myofibroblast proliferation, and reduction in oxidative stress and collagen deposition. These findings highlight ivermectin as a potential candidate for the management of fibrotic lung diseases, warranting further mechanistic and clinical investigations.