Vitexin Mitigates Bleomycin-Induced Pulmonary Fibrosis in Rats via Antioxidant, Anti-Inflammatory, Antiapoptotic, and Antifibrotic Mechanisms (Histological, Immunohistochemical, and Biochemical Study)

Bleomycin is a widely used antineoplastic glycopeptide antibiotic and chemotherapeutic agent that induces oxidative stress, inflammation, and apoptosis, causing life-threatening pulmonary fibrosis (PF). Therefore, the use of antifibrotic agents may prevent such complications. Vitexin is a flavone with potent antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic properties; however, its protective role against PF remains controversial. This study explores the mechanisms underlying vitexin-mediated protection against bleomycin-induced PF (BIPF). To unravel the relationship between bleomycin and lung fibrosis, a rat model of lung fibrosis was established for 28 days by dividing 28 male rats into 4 groups: control group (CG), vitexin-treated group (VTG received 6 mg/kg/day orally), bleomycin-treated group (BTG received a single intratracheal dose of bleomycin 3 mg/kg), and vitexin + bleomycin group (VBTG received the same doses as in the VTG and the BTG). All rats were sacrificed to assess histopathological (HP) changes using H&E, MTC, and Sirius Red; apoptotic changes using caspase-3 and TUNEL staining; and ultrastructural changes in the lung alveoli under LM and TEM. The work also evaluated the biochemical changes in antioxidant enzymes, proinflammatory cytokines, and fibrotic markers in lung homogenates from all groups. HP observations revealed significant lung tissue damage in the bleomycin group (lung fibrosis, increased apoptotic markers (caspase-3 and TUNEL), and disrupted ultrastructure of macrophages and type II pneumocytes). Furthermore, bleomycin substantially increased oxidative stress, proinflammatory cytokines, and fibrotic markers (indicating PF) in the lung homogenate of the BTG. On the contrary, vitexin’s supplementation significantly attenuated all HP features of lung tissue damage in the VBTG (anti-inflammatory, antiapoptotic, and fibrotic remodeling effects). Additionally, vitexin substantially mitigated all biomarker activities in the lung homogenate of the VBTG. These findings suggest that vitexin could be a protective dietary agent attenuating BIPF. However, further detailed clinical research is recommended to confirm these proposed preclinical protective findings of vitexin in clinical studies.