Amlodipine: Can act as an antioxidant in patients with transfusion‐dependent β‐thalassemia? A double‐blind, controlled, crossover trial

Abstract

Background and Aim: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent β-thalassemia (TDT) patients.Methods: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, μmol/L), carbonyl (protein CO, μM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, μmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo.Results: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was −0.59, 95% confidence interval [CI] −1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was −0.11, 95% CI −0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI −0.40 to 0.91, and 0.42, 95% CI −0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). Conclusion: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT. K E Y W O R D S amlodipine, malondialdehyde, oxidative stress, protein carbonyl, reactive oxygen species, redcell transfusion, β-thalassemia 2of10 | DARVISHI-KHEZRI et al. | INTRODUC TI ONThalassemia is well-known as the most prevailing hemoglobinopathy disorder globally. 1 Increased iron absorption and constant red-cell transfusions bring about iron overload in patients with transfusiondependent β-thalassemia (TDT). 2,3 Iron accumulation produces reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions in conjunction with the production of highly toxic hydroxyl radicals due to peroxidation. 4 ROS can damage lipids, proteins, deoxyribonucleic acid (DNA), and intracellular organelles, e.g., lysosomes and mitochondria. 5 This injury can lead to cellular dysfunction, apoptosis, and necrosis, leading to toxicity and dysfunction in the target organs. 6,7 Hydroxyl radical production and increased lipid peroxidation would be determining factors to trigger cardiac problems caused by iron surplus. [8][9][10] Various studies have shown that calcium channels are involved in iron absorption by myocardial cells. L-type calcium channel blockers (L-TCC blockers), e.g., amlodipine, are traditionally considered therapeutic options in arrhythmia and hypertension, which can inhibit calcium influx into the cell. According to studies, L-TCC blockers may reduce cellular iron uptake and oxidative stress, preventing iron damage. 11 Recent research has recommended amlodipine prescription to mitigate iron deposition into the tiss...

Amlodipine Therapy in β-Thalassemia Patients: A Systematic Review and Meta-Analysis on Ferritin Levels and Liver MRI T2*

“…Multiple mechanisms have been brought up for CCBs to exert antioxidant properties, including antithrombotic and anti-inflammatory properties. It is plausible that the chemical structure of these L-type CCBs contributes to their antioxidant properties [45,46].…”

“…Previously, we established that amlodipine therapy coupled with routine treatments with iron chelators could effectively benefit iron-overloaded transfusion-dependent thalassemia cases by lessening malondialdehyde (MDA) concentrations and the total antioxidant capacity (TAC) levels. Due to its ability to reduce NTBI uptake, amlodipine may be effective as a potential antioxidant, particularly when iron overload is present [46,47]. One of the underlying mechanisms explaining amlodipine's antioxidant properties is the control of intracellular calcium overload.…”