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Egyptian Journal of Medical Human Genetics

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L–Carnitine ameliorates the iron mediated DNA degradation in peripheral leukocytes of β-thalassemic children

SM Ragab, RG Mahfouz

Abstract


Background: Iron overload is a common complication in β-thalassemia that induces intracellular oxidative stress producing lesions in the DNA including double strand breaks. Objectives: The aim of this study was to evaluate DNA damage in peripheral leukocytes of β -thalassemic children and to investigate its association with the iron overload and the role of L-carnitine therapy upon this damage. Subjects and Methods: Fifty β-thalassemic children (25 TM and 25 TI) with 20 age and sex matched apparently healthy children (control group) were included. Serum ferritin level was measured by ELISA. DNA damage was evaluated by the Gel electrophoresis to determine the total DNA genomic damage (TGD). The intensity of DNA nucleoprotein was measured by software Gel Pro analyzer computer program as maximum optical density (max.O D) values of apoptotic fragments of DNA at 200bp, 400bp and 600bp. Results: The smear shape pattern on gel electrophoresis and Pro-Gel analyzer chart indicating double strand breakage of the DNA was detected in 76% of the thalassemic children. The thlassemic patients (the whole group and each of TM and TI groups) had significantly higher prevalence of DNA double -strand breaks in their leukocytes with significant higher values of max. OD at 200,400and 600 bp compared to the control group. The thalassemic children on regular L-carnitine therapy (50mg/kg/d for at least 6 months) had significantly lower prevalence and degrees of DNA breaks (TGD) with significant lower max. OD values at 200,400 and 600 bp compared to those not on L-carnitin therapy. There was significant positive correlation between the mean serum ferritin levels and the values of max. OD at 200 and 400bp. The data obtained from the Roc Curve shows that, the best sensitivity of 95% and specificity of 75% for the mean serum ferritin were at the cut off point of 820 ng/ml to predict the occurrence of TGD in thalassemic leukocytes. Conclusions: Thalassemic children had significant DNA double-strand breaks in their leukocytes that was positively correlated to their iron overload reflected by serum ferritin level and can be ameliorated by L-carnitine supplementation.

Key Words: β-Thalassemia, iron overload, oxidative stress, DNA damage, L-carnitine.




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