Abstract: PO0382
Curcumin Protects Lipopolysaccharide (LPS)-Induced AKI in Cirrhotic Mice
Session Information
- AKI: Mechanisms of Injury
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Gipson, Graham Thomas, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
- Gehr, Todd W., Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
- Ghosh, Shobha, Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
- Ghosh, Siddhartha S., Virginia Commonwealth University Medical Center, Richmond, Virginia, United States
Background
Cirrhotic patients frequently develop AKI in a variety of settings one of which is spontaneous bacterial peritonitis (SBP). Alteration in intestinal permeability associated with cirrhosis leads to leakage of inflammatory materials from the gut to circulation, aggravating AKI. Using our published model of AKI with cirrhosis and LPS injection mimicking SBP we show that curcumin improves hepatic and renal function by ameliorating alteration in intestinal permeability.
Methods
12 weeks biweekly oral gavage (1ml/kg) of carbon tetrachloride (CCl4) in mice induced cirrhosis. AKI was precipitated by injecting 2 mg/kg IP LPS one day before culling. The dose of LPS, chosen after careful titration, precipitated AKI only in cirrhotic mice. Animals were divided into four groups control (CO), CCl4, CCl4+LPS (CCl4+L), CCl4+LPS+Curcumin (CCl4+L+CU). CCl4+L+CU received 100 mg/kg CU for 12 weeks. FITC-dextran was administered a day before culling orally and blood levels assessed to determine intestinal permeability. Blood, urine, liver, and kidney were harvested to measure various parameters.
Results
BUN and creatinine of CCl4 and CCl4+L were significantly higher than CO however, a significant decrease of urinary sodium (50±8%, p<0.01) and urine output (70±9%; p<0.01) was seen only in the CCl4+L group. Liver injury markers SGOT and SGPT were significantly high in CCl4 and were even higher in CCl4+L. CU treatment (CCl4+L+CU) significantly improved all the liver and renal functions. Inflammasome markers NFkB, caspase 1, and IL-1β in the liver and kidney of CCl4 were significantly higher than the control which was further augmented in the CCl4+L group. There was a significantly increased absorption of FITC-dextran and decreased expression of tight junction proteins ZO 1 and claudin in the jejunum and ileum of CCl4 and CCl4+L cohorts suggesting increased intestinal barrier permeability. Curcumin treated, CCl4+L+CU group had decreased expression of inflammasome markers, decreased absorption of FITC-dextran, and increased expression of intestinal tight junction proteins.
Conclusion
Although curcumin has a significant anti-inflammatory property its systemic anti-inflammatory effect is limited by its poor bioavailability. We posit that curcumin by mitigating intestinal permeability reduces inflammatory burden in the circulation which helps in preserving liver and kidney function.