Abstract

Perfluorooctanoic acid (PFOA) exposure is associated with kidney dysfunction, however the exact mechanisms by which PFOA induces nephrotoxicity and the specific involvement of aquaporins (AQPs) in kidney tissue remains unclear. In this study, adult male Sprague-Dawley (SD) rats were exposed to PFOA by oral gavage for 28 days and compared with controls. Body weight, water intake and urine volume were recorded daily. At the end of the experiment, blood and kidney samples were collected, and serum urea, creatine and uric acid levels were assessed. The renal expression levels of water channel proteins AQP1, AQP3, AQP2 and p-AQP2 (Ser256) were observed by immunohistochemical staining, and the corresponding transcription levels were detected by Western blot and qRT-PCR. The results showed that PFOA exposure inhibited weight gain and increased water intake, urine volume, kidney weight and renal visceral index. PASM staining and transmission electron microscopy revealed pathological thickening of the glomerular capsule and basement membrane. Serum urea levels were increased, while serum creatine levels were decreased compared to controls. Additionally, the expression levels of AQP1, AQP3, AQP2 and p-AQP2 in kidney tissues were decreased, and the phosphorylation of AQP2 at Ser256 was inhibited. In conclusion, we demonstrate that PFOA exposure can damage the renal filtration barrier and reduce the expression level of AQPs in renal tissues, leading to renal filtration and reabsorption disorders.

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