Valproic acid protects septic mice from renal injury by reducing the inflammatory response

Abstract

Background: Valproic acid (VPA), a histone deacetylase inhibitor, has extensive activities against inflammation, oxidation, and malignancy. This study was designed to investigate the protective effect of VPA on the systemic inflammatory response and renal injury in septic mice.

Materials and methods: The septic model of mice was established using a cecal ligation-puncture technique. A single dose of VPA (300 mg/kg) was administered at 30 min postoperatively.

Results: We found that VPA reduced the tubular swelling and lowered the serum levels of blood urea nitrogen, creatinine, and C-reactive protein. After treatment with VPA, the renal level of malondialdehyde and the activity of myeloperoxidase decreased markedly; the activity of superoxide dismutase and the glutathione content increased accordingly; and the serum levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 decreased markedly. Furthermore, VPA suppressed the renal expression of cyclooxygenase 2 and inducible nitric oxide synthase and repressed the release of prostaglandin E2 and nitric oxide.

Conclusions: Our results demonstrate that VPA reduces the inflammatory response in a septic model and protects mice from renal injury, showing substantial potential in the treatment of sepsis.

Keywords: Inflammatory response; Renal injury; Sepsis; Valproic acid.