Accelerated liver recovery after acute CCl4 poisoning in rats treated with sodium phthalhydrazide

Int Immunopharmacol. 2020 Mar:80:106124. doi: 10.1016/j.intimp.2019.106124. Epub 2020 Jan 9.

Abstract

Pharmacotherapy of hepatobiliary disorders is an important issue due to the high prevalence of liver failure, toxic and viral hepatitis and cirrhosis. The number of stimuli that can potentially induce or accelerate liver recovery is limited; in our study we selected sodium phthalhydrazide, which has been found to promote liver regeneration after partial hepatectomy. We examined the effects of phthalhydrazide on liver morphometric, histological and biochemical parameters in rats intoxicated with CCl4. Accelerated liver recovery after CCl4 intoxication in phthalhydrazide-treated animals was evidenced by increased number of liver sinusoidal cells, reduced focal necrosis of hepatocytes and reduced perifocal leukocyte infiltration. Decreased plasma levels of pro-inflammatory cytokines TNF-α and IL-18 and decreased concentrations of IL-6 and IFN-γ in liver homogenates were associated with reduced severity of cholestasis and normalized hepatic protein synthesis in CCl4-intoxicated rats exposed to phthalhydrazide. Anti-inflammatory and immunomodulating properties of phthahlhydrazide can be an important factor contributing to accelerated liver recovery at early stages of acute CCl4-toxic liver impairment.

Keywords: Cytokines; Hepatoprotective pharmaceuticals; Liver recovery; Liver regeneration; Mast cells; Phthalhydrazide; Sinusoidal cells.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Carbon Tetrachloride
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / pathology
  • Cytokines / blood
  • Hydrazines / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Phthalazines / therapeutic use*
  • Protective Agents / therapeutic use*
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Hydrazines
  • Immunologic Factors
  • Phthalazines
  • Protective Agents
  • Carbon Tetrachloride