Abstract: FR-PO191
Antifibrotic Effects of Caffeic Acid in a Kidney Ischemia-Reperfusion Injured Mouse Model
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Capasso, Giovambattista, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
- Iervolino, Anna, University of Campania "L. Vanvitelli", Naples, Italy
- Zevola, Mario, University of Campania "L. Vanvitelli", Naples, Italy
- Miele, Antonio, University of Campania "L. Vanvitelli", Naples, Italy
- Iannaccone, Antonella, University of Campania "L. Vanvitelli", Naples, Italy
- Sasso, Benedetta, University of Naples Federico II, Naples, Italy
- Trepiccione, Francesco, University of Campania "L. Vanvitelli", Naples, Italy
- Perna, Alessandra, University of Campania "L. Vanvitelli", Naples, Italy
Background
Acute kidney disease due to renal ischemia/reperfusion (I/R) is a major clinical problem without effective therapies. The injured tubular epithelial cells may undergo epithelial–mesenchymal transition (EMT). The formation of scar tissue in the interstitial space during renal remodeling is caused by the excessive accumulation of extracellular matrix components and induced fibrosis. One of the primary causes of end-stage renal illness is renal tubulointerstitial fibrosis. In this work, we examined the effects of a natural phenolic antifibrotic drug, caffeic acid, on a mouse model of renal fibrosis.
Methods
I/R was induced by clamping bilaterally the renal artery and vein for 30 minutes. A single daily oral gavage of caffeic acid (40 mg/kg) was administered following the procedure. Renal fibrosis and kidney function were assessed 14 days later.
Results
The I/R treated with caffeic acid showed a recovery of renal function as compared to the other I/R groups analyzed. This was proven by a significant rise in urinary creatinine and urea excretion, along with a significant decrease in urine volume, serum creatinine, and proteinuria. Histological analysis, using Masson's trichrome and Picrosirius red staining, revealed that renal interstitial fibrosis and collagen deposition were elevated in I/R and significantly decreased in response to caffeic acid treatment, indicating the inhibitory role of caffeic acid on EMT. Then we investigated the effect of caffeic acid on myofibroblast activation markers, such a-SMA. After I/R, immunofluorescence showed a significant increase in a-SMA expression, which drastically decreased with the administration of caffeic acid. Moreover, using DHE, a fluorescent probe for the detection of Ros, specific for superoxide and hydrogen peroxide, we observed a reduction in Ros generation due to the caffeic acid treatment in the I/R group.
Conclusion
In conclusion, our study demonstrates that caffeic acid attenuates renal injury in an I/R animal model, preventing myofibroblast activation, ECM deposition, Ros generation, and renal interstitial fibrosis deposition.