Pachymic acid alleviates lipopolysaccharide-induced cystitis glandularis by inhibiting ferroptosis

BackgroundCystitis glandularis is a metaplastic lesion of the bladder mucosa. The underlying pathogenesis of cystitis glandularis and the potential association between the therapeutic effects of pachymic acid and ferroptosis remain unclear.MethodsHuman bladder epithelial cells (SV40-immortalized human urothelial cells-1 (SV-HUC-1)) and Sprague-Dawley rat bladders were treated with lipopolysaccharide, with pachymic acid and ferrostatin-1 used as interventions. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) assay. Levels of reactive oxygen species, glutathione, and malondialdehyde were quantified in both cells and tissues. Levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in rat bladder tissues were quantified using enzyme-linked immunosorbent assay kits. The expression levels of nuclear factor erythroid 2-related factor 2, glutathione peroxidase 4, and solute carrier family 7 member 11 were analyzed, and bladder inflammation was evaluated using hematoxylin and eosin staining. The mitochondrial ultrastructure of bladder tissue was examined using transmission electron microscopy.ResultsLipopolysaccharide treatment reduced cell viability, increased malondialdehyde and reactive oxygen species levels, and decreased glutathione levels in both cells and tissues. The levels of nuclear factor erythroid 2 related factor 2, glutathione peroxidase 4, and solute carrier family 7 member 11 were reduced, while those of inflammation markers were elevated. Lipopolysaccharide stimulation induced mitochondrial structural damage in rat bladder tissues. Treatment with pachymic acid and ferrostatin-1 partially reversed these effects.ConclusionsFerroptosis plays a critical role in lipopolysaccharide-induced cystitis glandularis. Pachymic acid may alleviate cystitis glandularis by inhibiting ferroptosis, offering a novel therapeutic strategy for the clinical management of this disease.