Exploring testosterone’s impact on pulmonary health in a rat model of COPD: Investigating MMP-9 and FGF-23

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disorder with limited treatment options targeting its underlying pathophysiology. This study investigates the therapeutic effects of testosterone on lung function and inflammation in a male rat model of COPD, focusing on matrix metalloproteinase-9 (MMP-9) and fibroblast growth factor-23 (FGF-23), biomarkers linked to tissue remodeling and systemic inflammation. Sixty male Wistar rats were assigned to control, COPD, and testosterone-treated groups. COPD was induced by lipopolysaccharide instillation and cigarette smoke exposure; testosterone was administered via subcutaneous implants. Pulmonary function tests, histopathology, bronchoalveolar lavage fluid (BALF) analysis, and biochemical assays were performed. Testosterone significantly improved forced vital capacity, FEV100, and mid-expiratory flow compared to the COPD group. Histology showed reduced alveolar wall thickening and inflammatory infiltration. Testosterone-treated rats exhibited lower neutrophil counts and malondialdehyde levels in BALF, along with increased superoxide dismutase activity, indicating reduced oxidative stress. At the molecular level, testosterone suppressed MMP-9 and FGF-23 expression at both mRNA and protein levels and significantly decreased MMP-9 enzymatic activity, as confirmed by gelatin zymography. These results suggest that testosterone alleviates pulmonary damage and inflammation by modulating oxidative stress and inhibiting key molecular mediators of COPD progression. This study supports the potential of testosterone as an adjunct therapy in COPD by improving respiratory function and reducing inflammation.