Perfluorooctanoic acid (PFOA), a persistent per- and polyfluoroalkyl substance, is widely detected in environmental and biological systems and has been associated with renal toxicity. However, the integrated relationship between oxidative stress, erythropoietic regulation, angiogenic signaling, and fibrotic remodeling remains insufficiently defined. This study evaluated dose- and duration-dependent nephrotoxic effects of sub-chronic PFOA exposure in male Wistar albino rats. Animals received oral administration of PFOA at 48 or 96 mg/kg body weight over exposure periods of 30, 60, and 90 days. Renal toxicity was assessed using serum biochemical markers, hematological parameters, electrolyte levels, and erythropoietin concentration. Oxidative stress was evaluated through lipid peroxidation and antioxidant enzyme activities. Histopathological changes were examined using hematoxylin-eosin, Masson's trichrome, Periodic Acid-Schiff, and Alcian blue staining, while immunohistochemistry was performed for Vimentin and vascular endothelial growth factor (VEGF). PFOA exposure resulted in significant renal dysfunction, including increased serum urea, uric acid, and blood urea nitrogen levels, accompanied by enhanced lipid peroxidation and reduced antioxidant defenses (p < 0.05). Histological examination revealed glomerular atrophy, tubular degeneration, inflammatory infiltration, and collagen deposition. Increased Vimentin expression and reduced VEGF immunoreactivity indicated epithelial-mesenchymal transition and impaired angiogenic signaling. Collectively, the findings demonstrate that PFOA-induced nephrotoxicity involves coordinated disruption of redox balance, hypoxia-responsive signaling, and angiogenic pathways rather than isolated oxidative injury. This integrative framework provides mechanistic insight into PFAS-associated renal disease and identifies the erythropoietin-VEGF axis as a potential target for early intervention.
Hongal et al. (2026) studied this question.