Abstract: FR-PO1024
AQP7 as a Novel Marker of p-Cresol-Induced Renal Cell Damage: Beneficial Effects of Hydroxytyrosol and a Polyphenolic Enriched Complex Derived from Olive Oil Mill Wastewater
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Angelini, Ines, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Centrone, Mariangela, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- D'Agostino, Mariagrazia, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Semeraro, Daniela, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Mastrodonato, Maria, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Caponio, Giusy Rita, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Di Mise, Annarita, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Ranieri, Marianna, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Valenti, Giovanna, Universita degli Studi di Bari Aldo Moro, Bari, Italy
- Tamma, Grazia, Universita degli Studi di Bari Aldo Moro, Bari, Italy
Background
p-cresol, a gut microbiota-derived uremic toxin, is related to renal injury and Chronic Kidney Disease (CKD). Nevertheless, the molecular mechanisms causing renal damage are still far from being clarified. Here, the actions of p-cresol and the beneficial effects of a polyphenolic enriched complex (Momast®) and hydroxytyrosol were evaluated.
Methods
Human proximal tubular kidney cells (HK-2) were used as an experimental cell model. Several cell stress biomarkers were assayed, including Reactive Oxygen Species (ROS) generation and Oil Red O lipid droplets formation. Gene and protein expression was tested by Real Time PCR and Western Blotting.
Results
Exposure of HK-2 cells to p-cresol (100 µM for 24 hours) caused a significant increase in ROS content and polymerization of the actin cytoskeleton. Moreover, a significant accumulation in lipid droplets was found as well. Interestingly, Real Time PCR and Western Blotting analysis revealed that p-cresol significantly upregulates the expression of the aquaglyceroporin AQP7. Notably, selective inhibition of AQP7 using Z433927330 prevented the p-cresol-induced lipid droplets storage. Of interest, the harmful actions induced by p-cresol were reversed by treating cells with Momast®, a natural complex derived from olive oil mill wastewater enriched with hydroxytyrosol (HT), which is filtered by the kidney and recovered in the urine. Preliminary data revealed that HT itself also prevents the p-cresol-induced AQP7 increase.
Conclusion
Altogether these findings propose for the first time AQP7 as a novel target related to p-cresol exposure. Selective inhibition of AQP7 significantly decreased lipid droplets accumulation, which is known to be correlated with renal cell injury. Additionally, treatment with Momast® prevented the effects induced by p-cresol. Moreover, obtained data indicate HT as a possible natural coadjuvant to counteract renal cellular injuries induced by p-cresol.
Funding
- Government Support – Non-U.S.