Abstract: FR-PO139

Vitamin C Therapy Attenuates the Severity of AKI in Mice Model of Hepatorenal Syndrome

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Yousef, Nadia, VCU Medical Center, GLEN ALLEN, Virginia, United States
  • Ghosh, Siddhartha S., VCU Medical Ctr, Richmond, Virginia, United States
  • Carl, Daniel E., None, Richmond, Virginia, United States
Background

Hepatorenal syndrome (HRS) type 1 is a life threatening complication of cirrhosis with limited therapeutic options and it manifests when an acute insult leads to renal vasoconstriction and secondary impairment of glomerular filtration in the setting of liver disease. There are unfortunately few therapeutic options to offer. A significant limitation in HRS research is the lack of animal models investigating the pathophysiology of HRS as well as potential beneficial therapies. We hypothesized that Vit C has a protective effect in HRS. We tested this hypothesis in murine model of HRS.

Methods

C57BL6 mice received 1ml/kg of carbon tetrachloride (CCl4) biweekly for 12 weeks to induce cirrhosis. A 6 mg/Kg of Lipopolysaccharide (LPS) was given intraperitoneally to induce acute kidney injury by simulating the inflammatory stressor caused by acute infection. Vit C 200 mg/kg was given 15 min prior to LPS. Four mice populations were studied:
1. Control mice (received Vit C only)
2. CCl4 treated mice
3. CCl4 + LPS mice
4. CCl4+LPS+Vit C mice (N=4-6 per group).
Serum BUN, creatinine, urine output and urinary Na+ were measured in all 4 groups. MCP-1 and NFkB proteins expression were determined by western blot. Plasma IL-6 was measured by ELISA

Results

Control group 1 received Vit C only and showed the ideal BUN, SrCr and urine output. CCl4+LPS treated mice had renal phenotype suggestive of HRS, including a higher SCr, lower UNa and UOP compared to CCl4 mice (p<0.05). Vit C treated mice in group 4 showed significant improvement in renal function, as CCl4+LPS+Vit C mice had a significant improvement SCr and UNa+ (p<0.05) compared with CCl4+LPS mice, and there was a trend towards an improvement in UOP (p 0.07). MCP-1 protein expression was significantly higher (p<0.05) in CCl4+ LPS group compared with control and with the CCl4+LPS+Vit C group. Moreover, NFkB protein expression was significantly higher (p<0.05) in CCl4+LPS compared to the control group and CCl4+LPS+Vit C

Conclusion

Vit C administration has a protective role in severity of HRS, manifested by improved SCr, UOP, and UNa+ in this model of HRS. One potential etiology is via inflammation, as pre-treatment with Vit C down-regulates both inflammatory markers.