Amygdalin (Vitamin B17) pretreatment attenuates experimentally induced acute autoimmune hepatitis through reduction of CD4+ cell infiltration

Ann Anat. 2019 Jul;224:124-132. doi: 10.1016/j.aanat.2019.04.006. Epub 2019 May 15.

Abstract

Background: Autoimmune hepatitis (AIH) is an immune-mediated inflammation of the liver characterized by disorganized hepatic parenchyma and inflammatory cell infiltration. Although the increased incidence of AIH, the development of novel therapeutic strategies are impeded by the poor understanding of the accompanied detailed immunopathogenic changes. CD4+ T cells are key mediators of inflammatory cell infiltration in initial phases of liver injuries like AIH. The distribution of CD4+ cells and the histopathological changes accompanying Con A-induced AIH were investigated together with the postulated protective effect of Amygdalin (Amg.).

Materials and methods: 30 adult male mice were divided into three groups; control, AIH and AIH-Amg. groups. AIH was induced by a single intravenous injection of Concanavalin A (Con A) (15 mg/kg). The AIH-Amg. group received Amg. 5 mg/kg intraperitoneally once a week for three weeks. Blood samples were examined for ALT and AST. MDA, SOD, and GSH were determined in hepatic homogenates. Liver section stained with hematoxylin and eosin, Masson trichrome and CD4+ immune stain were examined by light and electron microscopy.

Results: AIH group showed a significant increase in levels of ALT, AST and MDA and a significant decline in SOD and GSH compared to the controls. The liver tissue showed distorted hepatic architecture with intercellular hemorrhage, necrosis, and inflammatory cell infiltration. The area percent of CD4+ immune staining was significantly increased. Electron microscopic examination showed massive cellular degenerative changes. Amg. pretreatment in AIH-Amg. group significantly reversed these changes.

Conclusion: AIH induced CD4+ cells infiltration in the liver with subsequent liver tissue damage. Amg. pretreatment inhibited CD4+ cell infiltration and protected the liver tissue. This finding suggests that Amg. could be a therapeutic agent in the management of AIH.

Keywords: Amygdalin; Autoimmune hepatitis; CD4+ cells.

MeSH terms

  • Alanine Transaminase / blood
  • Amygdalin / administration & dosage*
  • Analysis of Variance
  • Animals
  • Aspartate Aminotransferases / blood
  • CD4-Positive T-Lymphocytes / drug effects*
  • Concanavalin A / adverse effects
  • Glutathione / metabolism
  • Hepatitis, Autoimmune / drug therapy*
  • Hepatitis, Autoimmune / etiology
  • Hepatitis, Autoimmune / immunology
  • Hepatitis, Autoimmune / prevention & control
  • Immunohistochemistry
  • Liver / drug effects
  • Liver / immunology*
  • Liver / pathology*
  • Liver / ultrastructure
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mitogens / adverse effects
  • Oxidative Stress
  • Superoxide Dismutase / metabolism

Substances

  • Mitogens
  • Concanavalin A
  • Amygdalin
  • Malondialdehyde
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione