Abstract: FR-PO975
Scavenging Lipid Oxidation Products Improves Intestinal Inflammation and Integrity After Renal Injury
Session Information
- CKD: Pathobiology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Davies, Sean Stephen, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Kidney disease affects intestinal structure and function. We previously showed that kidney injury amplifies intestinal lymphangiogenesis and increases mesenteric lymph flow that enhances systemic delivery of gut-originating harmful substances, including the highly reactive product of lipid oxidation, isolevuglandin (IsoLG). IsoLG is best known for its harmful effects to modify apolipoprotein A-I(apoAI)/high-density lipoprotein (HDL) which promotes atherosclerosis. 2-Hydroxybenzylamine (2-HOBA) is a selective scavenger of IsoLG that protects proteins and lipids from being modified. Since oxidation and lipoprotein modification prevails across the entire spectrum of kidney disease, we investigated the potential benefit of 2-HOBA on intestinal disruption following kidney injury.
Methods
Puromycin nephrotoxicity (PAN) was induced in Sprague Dawley rats, while saline-injected rats served as control (Cont). Half of the PAN rats were treated with water containing 2-HOBA (1 g/L). Eight days after induction of PAN injury, mesenteric lymph, intestine, blood, and urine were collected for analysis.
Results
PAN rats had significant proteinuria and ascites. Mesenteric lymph of PAN injured rats contained 1.8-fold higher level of IsoLG-modified apoAI vs Cont which was decreased by 63% in mesenteric lymph of 2-HOBA treated rats. PAN increased macrophage infiltration, evidenced by greater number of CD68-positive cells which was lessened by 2-HOBA. PAN injury caused a significant increase in intestinal expression of inflammatory genes, including monocyte-chemoattractant protein-1, interleukin 17A, interleukin 10, and tumor necrosis factor-alpha vs Cont. Vascular cell adhesion molecule 1 which maintains intestinal integrity was also increased in PAN vs Cont. All these injury-driven changes were attenuated by 2-HOBA.
Conclusion
Scavenging the lipid oxidation product lessened kidney injury-induced mesenteric lymph IsoLG modification of apoAI together with reduction in intestinal inflammation and disruption of integrity. Our data support a novel therapeutic approach to CKD provoked intestinal dysfunction.
Funding
- NIDDK Support