Abstract: SA-PO840
Sodium Butyrate Alleviates Renal Failure (RF) in Animals by Mitigating Inflammation and Fibrosis
Session Information
- Molecular Mechanisms of CKD - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Gonzalez, Austin J., Virginia Commonwealth University, Fredericksburg, Virginia, United States
- Ghosh, Siddhartha S., VCU Medical Ctr, Richmond, Virginia, United States
- Krieg, Richard, VCU, Richmond, Virginia, United States
- Gehr, Todd W., Virginia Commonwealth University, Fredericksburg, Virginia, United States
Background
Renal failure (RF) is largely associated with inflammation and damage of kidney tissue. NFkB is a well-known marker for inflammation and for the regulation of fibrosis. Phosphorylated NFkB (pNFkB) is translocated into the nucleus and promotes transcription of various genes which play a role in inflammation and fibrosis. Treatment with sodium butyrate, a short-chain fatty acid (SCFA) and histone deacetylase (HDAC) inhibitor, has been shown to have anti-inflammatory effects in RF. We demonstrate that sodium-butyrate treatment can ameliorate RF at both the biochemical and histopathological level.
Methods
Five-sixth nephrectomized Sprague-Dawley rats were used as a model for RF. Animals were divided into three groups: Sham-operated control (SH), untreated nephrectomy (Nx), and nephrectomy with butyrate treatment (Nx+BU) 100 mg/kg/day sodium butyrate in drinking water. Kidney tissue cytosolic NFkB and nuclear pNFkB were measured by Western Blot analysis. Histological analysis was performed on the kidney tissues with both Periodic Acid-Schiff stain and Picro-Sirius Red stain to measure the extent of collagen networks in fibrosis. Renal biomarkers were measured by chemical assay.
Results
There was 3.5 fold increased translocation of pNFkB in the nucleus of Nx rats, which was significantly lowered in the Nx+BU group. There was no difference in cytosolic NFkB. Kidney tissue of the Nx animals had 35±4.4% segmental sclerosis, whereas Nx+BU animals had reduced to 24±5.6% (p=0.003). In Nx, 26% of the area was positively stained with sirius red compared to 1.7% in SH (p<0.0001), but was reduced by 50% in Nx+BU (p<0.01). The serum urea, urinary protein/creatinine ratio, and serum creatinine of Nx rats were significantly higher (3.6, 3, and 3.2-fold respectively) than SH. Nx+BU had significantly improved proteinuria and serum urea levels. Serum creatinine levels were reduced by 22% in Nx+BU (p=0.05).
Conclusion
Treatment with sodium butyrate has been shown to have beneficial effects on the translocation of NFkB, subsequent histological data on kidney fibrosis, and renal function in RF. Sodium butyrate, among other systemic and gut-related benefits, acts as an HDAC inhibitor and provides a possible mechanism for anti-inflammatory action in RF.