Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia-Reperfusion Injury Model

Abstract EN

Ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI).

At present, there are no effective therapies to prevent AKI.

The aim of this study was to analyse whether valproic acid (VPA), a histone deacetylase inhibitor with anti-inflammatory properties, prevents renal IRI.

Male Wistar rats were divided into three groups: SHAM rats were subjected to a SHAM surgery, IRI rats underwent bilateral renal ischemia for 45 min, and IRI + VPA rats were treated with VPA at 300 mg/kg twice daily 2 days before bilateral IRI.

Animals were euthanized at 48 hours after IRI.

VPA attenuated renal dysfunction after ischemia, which was characterized by a decrease in BUN (mg/dL), serum creatinine (mg/dL), and FENa (%) in the IRI + VPA group ( 39 ± 11 , 0.5 ± 0.05 , and 0.5 ± 0.06 , resp.) compared with the IRI group ( 145 ± 35 , 2.7 ± 0.05 , and 4.9 ± 1 , resp.; p < 0.001 ).

Additionally, significantly lower acute tubular necrosis grade and number of apoptotic cells were found in the IRI + VPA group compared to the IRI group ( p < 0.001 ).

Furthermore, VPA treatment reduced inflammatory cellular infiltration and expression of proinflammatory cytokines.

These data suggest that VPA prevents the renal dysfunction and inflammation that is associated with renal IRI.