title: Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia.
abstract: This study aimed to assess antioxidant effects of melatonin treatment compared to N-acetylcysteine (NAC) and to their combination in a sickle cell suspension. Sickle erythrocytes were suspended in phosphate-buffered saline, pH 7.4, composing external control group. They were also suspended and incubated at 37°C either in the absence (experimental control group) or in the presence of NAC, melatonin and their combination at concentrations of 100 pm, 100 nm and 100 μm for 1 hr (treatment groups). The melatonin influences were evaluated by spectrophotometric [hemolysis degree, catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), and superoxide dismutase (SOD) activities] and chromatographic methods [glutathione (GSH) and malondialdehyde (MDA) levels]. Incubation period was able to cause a rise about 64% on hemolysis degree as well as practically doubled the lipid peroxidation levels (P < 0.01). However, almost all antioxidants tested treatments neutralized this incubation effect observed in MDA levels. Among the antioxidant biomarkers evaluated, we observed a modulating effect of combined treatment on GPx and SOD activities (P < 0.01), which showed ~25% decrease in their activities. In addition, we found an antioxidant dose-dependent effect for melatonin on lipid peroxidation (r = -0.29; P = 0.03) and for combined antioxidant treatments also on MDA levels (r = -0.37; P = 0.01) and on SOD activity (r = -0.54; P < 0.01). Hence, these findings contribute with important insight that melatonin individually or in combination with NAC may be useful for sickle cell anemia management.
authors.affiliation: Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, UNESP - Sao Paulo State University, Sao Paulo, Brazil; Department of Chemistry and Environmental Sciences, UNESP - Sao Paulo State University, Sao Paulo, Brazil.
authors.forename: Danilo Grünig Humberto
authors.initials: DG
authors.lastname: da Silva
authors.forename: Octávio
authors.initials: O
authors.lastname: Ricci
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: de Almeida
authors.forename: Claudia Regina
authors.initials: CR
authors.lastname: Bonini-Domingos
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000975:Antioxidants / Q000627:therapeutic use*; D002374:Catalase / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D005980:Glutathione Reductase / Q000097:blood; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D000975:Antioxidants; D006451:Hemoglobin, Sickle; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D008550:Melatonin
keywords: alternative therapy; antioxidant capacity; hemoglobin S; melatonin; oxidative stress