Apoptosis in thalassemia major reduced by a butyrate derivative.
OBJECTIVE
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.


CONCLUSIONS
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.
El-Beshlawy
A
A
Pediatric Department, School of Medicine and Al Azhar Universities, Cairo, Egypt.
Seoud
H
H
Ibrahim
A
A
Youssry
I
I
Gabre
H
H
Isma'eel
H
H
Aoun
E
E
Taher
A
A
D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002331:Carnitine / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D053938:DNA Fragmentation / Q000187:drug effects; D004900:Erythroblasts / Q000187:drug effects / Q000473:pathology; D005260:Female; D006401:Hematologic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009707:Nucleosomes / Q000187:drug effects / Q000473:pathology; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000473:pathology*
D006401:Hematologic Agents; D009707:Nucleosomes; D002331:Carnitine