Sodium valproate, a histone deacetylase inhibitor, with praziquantel ameliorates Schistosoma mansoni-induced liver fibrosis in mice

Abstract

Aims: This study explores the potential antifibrotic effect of sodium valproate (SV), an inhibitor of class I histone deacetylase (HDAC) enzymes, and/or praziquantel (PZQ) on Schistosoma mansoni (S. mansoni)-induced liver fibrosis in mice.

Main methods: Male Swiss albino mice were divided into nine groups: group I- normal control (NC); group II- uninfected gum mucilage (GM) treated; group III- uninfected PZQ- treated; group IV- uninfected SV-treated; group V- control S. mansoni infected mice; group VI- infected GM-treated; group VII- infected PZQ-treated; group VIII- infected SV-treated; group IX- infected PZQ+SV treated. All SV administrations were 300mg/kg/day orally and administered for five weeks beginning on the 5th week post infection (WPI). All PZQ administrations were 500mg/kg/day orally and administered for 2 consecutive days beginning on the 7th WPI. Serum transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), hepatic hydroxyproline (Hyp) content, and liver function tests (AST and ALT) were determined. Specimens of the hepatic tissues were examined histologically.

Key findings: Treatment of S. mansoni-infected mice with SV significantly decreased the serum levels of ALT, TGF-β1 and TNF-α, and the liver tissue hydroxyproline content compared with the S. mansoni infected untreated groups. Histologically, treatment with SV revealed regression of the granulomatous inflammatory reaction. Combined treatment with PZQ and SV produces more favorable biochemical results, and aborted granulomatous reaction compared with either drug alone.

Significance: Sodium valproate is a promising anti-fibrotic agent. It demonstrated an anti-fibrotic effect in early stages of S. mansoni infection through downregulation of profibrogenic cytokines, and collagen deposition.

Keywords: Histone deacetylase inhibitors; Liver fibrosis; Praziquantel; Schistosoma mansoni; Sodium valproate.