Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.
J Surg Res
; 266: 222-229, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34023578
ABSTRACT
INTRODUCTION:
Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury.METHODS:
We analyzed data from two separate experiments where swine were subjected to lethal insults. Model 1 hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2 polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy.RESULTS:
VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1 80% vs 20%; Model 2 83% vs. 17%). Model 1 (Hemorrhage alone) Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma) Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment.CONCLUSIONS:
A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Traumatismo Múltiple
/
Ácido Valproico
/
Inhibidores de Histona Desacetilasas
/
Lesión Renal Aguda
/
Hemorragia
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Surg Res
Año:
2021
Tipo del documento:
Article