title: Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia-Reperfusion Injury Model.
abstract: 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.
authors.affiliation: Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Elerson C
authors.initials: EC
authors.lastname: Costalonga
authors.affiliation: Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Filipe M O
authors.initials: FM
authors.lastname: Silva
authors.affiliation: Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo, 01246-903 São Paulo, SP, Brazil; Center for Cellular and Molecular Studies and Therapy (NETCEM), University of São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Irene L
authors.initials: IL
authors.lastname: Noronha
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D014635:Valproic Acid