Therapeutic Potential of Propylparaben in Modulating Pathophysiological Features of Fabry Nephropathy

Background: Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient α-galactosidase A activity and progressive multi-organ damage, including renal failure. Although enzyme replacement therapy (ERT) is commonly used, disease progression persists in some patients. This study investigated the therapeutic potential of propylparaben (PP) in a murine model of Fabry disease, focusing on renal fibrosis, oxidative stress, inflammation, and albuminuria. Methods: Wild-type, untreated Fabry disease, and PP-treated Fabry disease mice were evaluated. Renal histopathology, inflammatory cytokine expression, oxidative stress markers, lipid peroxidation, and urine albumin excretion were analyzed. Results: Fabry disease mice exhibited pronounced renal interstitial fibrosis, as evidenced by trichrome and Sirius red staining, which was significantly reduced following 12 weeks of PP treatment. Elevated renal mRNA levels of pro-inflammatory cytokines IL-1β and IL-6 were downregulated in PP-treated mice. Additionally, PP treatment upregulated renal HO-1 protein expression and reduced 4-HNE levels, indicating decreased oxidative stress. Albuminuria, significantly increased in Fabry disease mice, was also reduced by PP treatment. Conclusion: Propylparaben ameliorates renal fibrosis, inflammation, oxidative stress, and albuminuria in a Fabry disease model. These findings support its potential as a novel therapeutic candidate for Fabry nephropathy, meriting further preclinical and clinical investigation. Funding: Private Foundation Support