Apoptosis in thalassemia major reduced by a butyrate derivative

Acta Haematol. 2005;114(3):155-9. doi: 10.1159/000087890.

Abstract

Background and objectives: In cases of beta-thalassemia major, apoptosis appears to be greatly enhanced in the early-stage erythroid precursors in the bone marrow leading to ineffective erythropoiesis. L-Carnitine is found to strongly reduce apoptosis in different diseases. We investigated the effect of oral L-carnitine therapy on apoptosis in thalassemia major patients.

Methods: Eighteen thalassemia major patients with a mean age of 12.2 +/- 6.6 years were included. Detection of apoptosis was done by photometric enzyme immunoassay (ELISA) and agarose gel electrophoresis before and after 6 months of oral therapy with L-carnitine (50 mg/kg/day).

Results: A significant decrease of apoptosis frequency in the erythroid precursors in the bone marrow of studied cases was noted after therapy. The quantity of nucleosomes measured by ELISA dropped from 3.65 +/- 1.338 to 1.60 +/- 0.65 after therapy (p = 0.005). A positive ladder pattern reflecting apoptosis on agarose gel electrophoresis was detected in 88.9% of cases prior to treatment versus 16.7% after therapy (p = 0.006). Patients also had a significant decrease in the frequency of transfusions and increase in the pre-transfusion hemoglobin levels after therapy.

Conclusion: L-Carnitine seems to be a good modulator of apoptotic processes in thalassemic patients leading to a decreased frequency of programmed erythroblast death and general improvement of the disease condition.

MeSH terms

  • Adolescent
  • Apoptosis / drug effects*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Carnitine / therapeutic use*
  • Child
  • Child, Preschool
  • DNA Fragmentation / drug effects
  • Erythroblasts / drug effects
  • Erythroblasts / pathology
  • Female
  • Hematologic Agents / therapeutic use*
  • Humans
  • Male
  • Nucleosomes / drug effects
  • Nucleosomes / pathology
  • beta-Thalassemia / drug therapy*
  • beta-Thalassemia / pathology*

Substances

  • Hematologic Agents
  • Nucleosomes
  • Carnitine