Beta thalassemia is the most prevalent type of genetic diseases to hemoglobin worldwide. Thalassemia is classified into alpha and beta thalassemia according to the globin chain whose synthesis is adversely affected [1]. Excess globin chain synthesis in thalassemia contributes to red blood cell damage, resulting in red blood cell loss in the bone marrow and peripheral circulation (hemolysis) [2]. The main course of treatment for these patients is continuous blood transfusion. Following blood transfusion, numerous organs, including the kidneys, liver, heart, and endocrine glands, have an excess of iron. Iron load can be terminated for this organ dysfunction and mortality. Free ferrous iron is extremely toxic and is typically bound to proteins in the liver. Free radicals that are implicated in hepatotoxicity and lipid peroxidation are created as a result of unbound iron over load. krill oil and aqueous thyme extract [3] increase the hepatoprotective activity through improvements in both liver tissue oxidative stress parameters, and histological features However, the most dangerous side effect of iron overload is heart toxicity, which can be fatal. Signs of renal impairment in thalassemia patients include elevated renal blood flow, abnormal urine concentrations, and renal tubular acidosis [4, 5].

Treatment strategies including reducing anemia, inhibiting gastrointestinal absorption of iron, and suppressing erythropoiesis. With frequent blood transfusions, there is a major risk of iron overload, which is fatal to the organs and tissues of thalassemia patients. To treat it, an iron chelator is used to eliminate iron pools from intracellular or plasma. After 10 to 20 transfusions or when serum ferritin levels are greater than 1000 ng/mL, beta thalassemia patients must begin iron chelation therapy. The FDA and the USA approved two iron chelates, which are primarily used for the removal of excessive iron. Deferasirox is administered orally, whereas deroxamine is administered parenterally or subcutaneously. Both are used by patients at the Thalassemia Center at Al Kut Teaching Hospital [6]. Toxicity of iron chelators (deferioxamine, deferiprone, deferasirox) can lead to liver and glomerular dysfunction [7, 8]. Kidney injury in thalassemia increases with age and duration of blood transfusions [9]. In patients with beta thalassemia, little attention has been paid to potential renal damage, but recent studies indicate the presence of various tubular and glomerular dysfunctions [10]. Deferoxamine (Desferal®), Novartis Europharm Basil, Switzerland which was derived from Streptomyces pilosus and first made available in 1960, was the first iron chelator. It was administered parenterally (intravenously or subcutaneously).

Deferoxamine (Desferal®) is administered subcutaneously, which causes severe pain at the injection site whereas prolonged intravenous administration leads to noncompliance and development retardation [11]. As a result, an oral iron chelator such as deferiprone or deferasirox is necessary. Deferiprone, a bidentate hydroxypyridone that was first introduced in 1980, is the first oral iron chelator. It works by binding to iron and then being excreted in the urine. Due to quick hepatic metabolism, deferiprone has a relatively short half-life and is taken at a dose of 75 mg/kg/day with a considerable decrease in intracellular iron overload. Deferiprone causes a number of adverse side effects, including arthralgia, gastrointestinal disturbances, liver damage, and agranulocytosis brought on by myelotoxicity [12]. Deferasirox (Xjade®), Novartis Europharm Switzerland a brand-new oral chelator, was made available in 2005 to treat beta-thalassemia major and intermedia patients who had iron overload [13]. This study aimed to determine the effect of these drugs on kidney, liver enzyme activities ((Serum Glutamic-pyruvic Transaminase (S.GPT), serum glutamic-oxaloacetic transaminase (S.GOT), S. Urea and S. Creatinine, and serum ferritin level in \(\beta\)-thalassemia patients major.

This study was a cross section study conducted from a Hereditary blood Disorders Center in Wasit province in September 2022 with known cases of \(\beta\)-thalassemia major treated regularly with blood transfusion and iron chelators (either Deferasirox (Exjade®) or Deferoxamine (Desferal®)); Both of them manufactured from Novartis Europharm- Basil, Switzerland, to compare between two groups of thalassemic patient ( 20 in each group) and evaluate the effects of iron chelators on hemoglobin, serum ferritin, renal (blood Urea, and serum Creatinine) and liver (S.GPT, S.GOT) function tests that regularly done to the patient at each visit for blood transfusion, . The patient’s age was in the range of 4-34 years (mean age of sample was 16.33\(\pm\)6.342 years).

The data were collected from the patients files available in the center, two measurements for laboratory parameters were included in the study (3 month time gap between first and second reading) to ensure more accurate comparison, the cases of beta-thalassemia major from both gender (55%males and 45%females) were diagnosed as having \(\beta\)-thalassemia major by specialist hematologist by hemoglobin electrophoresis. Patients were divided according to the type of therapy into two groups. Group A included 20 transfusion-dependent \(\beta\)-thalassemia patients receiving deferasirox (Xjade®) (an oral iron-chelating), and group B include 20 transfusion-dependent \(\beta\)-thalassemia patients receiving deferoxamine (Desferal®) as iron chelating agent, the exclusion criteria included patients with sepsis, heart failure, renal failure, active liver disease (hepatitis B or C). Ethical approval was obtained from the scientific committee in pharmacy department; Alkut university college. Verbal consent was obtained from the patients. Data were analyzed using SPSS 26 statistics software, (p-value less than 0.05 considered significant).

The thalassemic patients included in the study of both gender, females (45%) and males (55%) (as seen in Figure1). Mean age of sample was 16.33 \(\pm\) 6.342 years, the data categorized to four age groups, 12% were aged 5 to 10 years, 40% of sample were between 11 and 15 years, one-quarter were aged 15 to 20 years and the remnant were above 20 years (Figure [1]).

Figure 1: Gender Percent of the Patients and their Ages

There was a significant difference between serum ferritin for both readings (p- value <0.05) between the study groups however, there was no significant difference between study groups for both readings of hemoglobin (p- value >0.05). Both groups complain low level of hemoglobin. Urea and creatinine in both readings had no significant difference between deferoxamine (Desferal®) and deferasirox (Xjade®) groups. (p- Value >0.05). SGPT and SGOT values of the first reading showed no significant differences between deferoxamine (Desferal® and deferasirox (Xjade®) groups, while SGPT and SGOT values of the second reading showed significant differences between study groups , both SGPT and SGOT values were higher in patients received deferoxamine (Desferal®) than deferasirox (Xjade®), see Tables 1 and 2.

Beta thalassemia is the most common congenital hemolytic anemia due to partial or complete loss of \(\beta\)- globin chain synthesis that is characterized by severely ineffective erythropoiesis requiring regular red blood cell (RBC) transfusions to sustain life [14]. Iron chelating agents decrease the organ damages by chelate iron and excrete it out of the body. Without successful iron chelation therapy, patients are at risk f or iron accumulation in vital organs such as liver and heart [15]. The study involved 40 patients, males were slightly higher incidence than females. This is similar to previous Iranian study that showed percentage of males was 52% [19]. The serum ferritin levels in deferasirox (Xjade®) group showed significant decrease when compared with deferoxamine (Desferal®), this result are in agreement with Iraqi study performed by Althanoon and Alkazzaz [15]. Other study performed by Vichinsky et al. [16] showed a higher efficacy of deferasirox (Xjade®) compared to deferoxamine (Desferal®) in the minimization of iron overload in thalassemia. This difference may be due to higher efficacy and patients compliance of deferasirox (Xjade®) [17] since; deferoxamine (Desferal®) parenteral administration led to poor compliance and efficacy [18].

There was no significant difference between both readings of hemoglobin and this in line with other previous studies that showed similar result among hemoglobin level for both deferoxamine (Desferal® and deferasirox (Xjade®) [19, 20]. Low level of hemoglobin occurred due to thalassemia itself and no role for iron chelating agents.

Urea and creatinine levels were lower in deferasirox (Xjade®) groups in both readings, although had no significant difference with Desferal group, but it indicate the that the renal protection effects of deferasirox (Xjade®) is higher compared to deferoxamine (Desferal®), the means of both investigations were within normal range that mean iron chelating agents not disturbed the functions of kidney. This results similar to results of two studies performed by Al Haddad et al. [21] and Shfik et al. [22], who studied some laboratory tests for thalassemic patients at general hospitals in Palestine.

SGPT and SGOT levels of the first reading showed no significant differences in both iron chelating groups, while SGPT and SGOT levels of the second reading were significantly decreased in deferasirox (Xjade® group, indicating that deferasirox (Xjade®) may be more effective in reducing hepatic damage than deferoxamine (Desferal®) in thalassemic patients due to their superior iron chelating effect compared to deferoxamine (Desferal®), deferasirox (Xjade®) showed significant decrease in the concentration of serum ferritin in body and this led to decrease iron overload in liver and improve its functions [19], this finding was compatible with two studies that showed deferasirox (Xjade®) is more effective in reduction of liver iron and improve myocardium and liver health [23, 24, 25].

There are some limitations in our study, the data were collected from single center, the small size of the sample.

Repeated blood transfusions is a major risk of iron overload, which damage the organs and tissues of thalassemia patients, our study indicated that deferasirox (Xjade®) is more effective than deferoxamine (Desferal®) in the treatment of iron overload and hepatoprotection in thalassemic patients, and that the using of deferasirox (Xjade®) decreases effects of iron on vital organs and minimizes the rate of complications in thalassemia patients.

Our thanks to patients who support us and cooperate with us through all stages of our study. Finally, we would like to thank God for letting us through all difficulties.

This research paper received no external funding.

The authors declare no conflicts of interest.

All authors contributed equally to this paper. They have all read and approved the final version.

Informed consent was obtained from all participates in the study as needed.

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