Serum melatonin level and oxidative stress in sickle cell anemia Eliana Litsuko Tomimatsu Shimauti a,b , Danilo Grunig Humberto Silva a,c , Eduardo Alves de Almeida c , Paula Juliana Antoniazzo Zamaro a , Edis Belini Junior a , Claudia Regina Bonini-Domingos a, ⁎ a UNESP - Sao Paulo State University, Biology Department, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil b UEM - Maringa State University, Department of Clinical Analysis, Parana, Brazil c UNESP - Sao Paulo State University, Department of Chemistry and Environmental Sciences, Sao Paulo, Brazil abstract article info Article history: Submitted 27 July 2010 Revised 23 August 2010 (Communicated by Sir D. Weatherall, F.R.S., 26 August 2010) Keywords: Sickle cell anemia Antioxidant capacity Melatonin This study evaluated serum melatonin levels in patients with sickle cell anemia (SCA) and compared the results to lipid peroxidation by determining thiobarbituric acid-reactive substances (TBARS) and Trolox equivalent antioxidant capacity (TEAC). The group studied was composed of 15 SCA patients and 24 subjects without hemoglobinopathies. The average melatonin level was significantly reduced in the SCA patients (p b 0.001) when compared to the control group. The SCA patients showed significantly higher values for TBARS and TEAC when compared to values obtained for the control group (p b 0.001 and p b 0.01). Results from the correlation analysis in the SCA group were not statistically significant for any parameters except for TBARS and TEAC levels, which had a positive correlation (r = 0.51; p = 0.04), suggesting the participation of melatonin in antioxidant defense. The use of melatonin could be a possible therapeutic target for improving antioxidant defense and to reduce oxidative damage, alleviating symptoms associated with SCA. © 2010 Elsevier Inc. All rights reserved. Introduction Sickle cell anemia (SCA), an inherited monogenic disease, is caused by a transversion in the codon of the sixth amino acid of the β-globin chain, on chromosome 11 [1], resulting in the formation of a structurally abnormal hemoglobin S (Hb S) that in its deoxygenated state tends to aggregate into rodlike polymers, resulting in the deformed sickle shape and rigidity of red cells characteristic of this condition [2]. SCA is often associated with oxidative stress due to increases in the generation of reactive oxygen species (ROS), which contributes to the proinflammatory, pro-thrombotic, and vaso-occlusive state of the disease, and which sometimes leads to increases in antioxidant defenses [3,4]. It has been proposed that melatonin has antioxidant properties [5–8]. The importance of melatonin as an antioxidant is also due to its capacity to cross biological barriers, which eases the removal of ROS in different biological compartments [9,10]. Clinical and experimental studies show that melatonin exerts both anti- inflammatory effect and immunoregulatory activity by inhibiting prostaglandin, tumor necrosis factor alpha, and interleukin-8 biosyn- thesis. In addition, melatonin stimulates the activities of enzymes that metabolize reactive species [11–13]. No reports of melatonin levels or their correlation with oxidative stress parameters in SCA have been found in the literature. Therefore, the goal of this study was to evaluate serum melatonin levels, plasma Trolox equivalent antioxidant capacity (TEAC), and lipid peroxidation (TBARS) in SCA patients when compared to a control group (Hb AA). Methods Subjects Thirty-nine subjects (25 males and 14 females; mean age: 26.2 years old; range: 10–55 years old) from the northwestern region of Paraná state in Brazil were studied. The test group was composed of 15 SCA patients, and the control group was composed of 24 subjects without hemoglobinopathies. The subjects were screened using a questionnaire and were excluded if they were smokers, drinkers, and had had a stroke or pain and hemolytic crisis in the last two months or were taking medication known to affect melatonin production, such as β-adrenergic blockers. All subjects gave their informed consent, and the study was approved by the ethics of human experimentation committee using the guidelines established by the National Health Ministry of Brazil. The Hb S group was composed of individuals receiving conventional treatment for SCA, including transfusion, folic acid, and hydroxyurea (HU), which can affect the Hb F values. The SCA patient phenotypes and clinical characteristics are provided in Table 1. Biological samples Blood samples (20 mL) were collected through venipuncture between 6:30 am and 7:30 am. The heparinized blood (7 mL) was Blood Cells, Molecules, and Diseases 45 (2010) 297–301 ⁎ Corresponding author. UNESP - Universidade Estadual Paulista “Julio de Mesquita Filho” - IBILCE, Biology Department, Hemoglobin and Hematologic Genetic Diseases Laboratory, Rua Cristóvão Colombo, 2265 - Jardim Nazareth, CEP: 15054-000 São José do Rio Preto - São Paulo - Brazil. E-mail address: claudiabonini@sjrp.unesp.br (C.R. Bonini-Domingos). 1079-9796/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.bcmd.2010.08.013 Contents lists available at ScienceDirect Blood Cells, Molecules, and Diseases journal homepage: www.elsevier.com/locate/ybcmd