Abstract: PUB388
Effects of Sigma-1 Receptor Antagonist Drugs on Renal Function and Fibrosis in a Preclinical Model of CKD
Session Information
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Jimenez Hurtado, Kiara Isabela, Universidad de Guadalajara Centro Universitario de los Altos, Tepatitlan de Morelos, Mexico
- Macias Barba, David, Universidad de Guadalajara Centro Universitario de los Altos, Tepatitlan de Morelos, Mexico
- Navarro, Vanesa, Universidad de Guadalajara Centro Universitario de los Altos, Tepatitlan de Morelos, Mexico
- Velasco, Alejandro, Universidad de Guadalajara Centro Universitario de los Altos, Tepatitlan de Morelos, Mexico
- Gutierrez-Mercado, Yanet Karina, Universidad de Guadalajara Centro Universitario de los Altos, Tepatitlan de Morelos, Mexico
- Echavarria, Raquel, Secretaria de Ciencia, Humanidades, Tecnologia e Innovacion, Mexico, Mexico
Background
Fibrosis is a common manifestation of chronic kidney disease (CKD). Sigma-1 receptor (S1R) antagonist drugs have been shown to inhibit myofibroblasts, generating an antifibrotic effect in heart and lung models, mediated through S1R. Yet, it is still unknown how S1R modulation affects kidney fibrosis and CKD development.
Methods
Female and male C57BL/6 mice underwent unilateral ureteral obstruction or Sham surgery and received 0.9% saline, NE-100 (1 mg/kg), or Haloperidol (2 mg/kg). At day 12 post-surgery, urea levels were determined and PAI-1, Col1a1, Acta2, and Txncd5 gene expression was analyzed with RT-PCR. Fibrosis was measured with the Sirius red histological stain.
Results
S1R antagonists had significant effects on kidney function by decreasing blood BUN levels in both sexes and PAI-1 expression only in females. It also reduced the area composed of collagen fibers, with NE-100 being superior to haloperidol in this regard.
Conclusion
The use of S1R antagonists has potential as a therapy for chronic kidney disease by improving kidney function and reducing fibrosis. However, some cases occur only in females, so further research is needed to address these uncertainties.
Fig1. S1R antagonists on renal function. (A) BUN (mg/dL). (B) Fold-change determined by RT-qPCR, N = 4
Fig2. S1R antagonist on fibrosis. (A) Kidney sections stained with Sirius red and (B) % positive area. (C) Fold-change determined by RT-qPCR. N=4