title: Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia.
abstract: This study evaluated the oxidative stress and antioxidant capacity markers in sickle cell anemia (SCA) patients with and without treatment with hydroxyurea. We assessed GSTT1, GSTM1 and GSTP1 polymorphisms in patients and a control group. The study groups were composed of 48 subjects without hemoglobinopathies and 28 SCA patients, 13 treated with HU [SCA (+HU)], and 15 SCA patients not treated with HU [SCA (-HU)]. We observed a significant difference for GSTP1 polymorphisms in SCA patients with the V/V genotype that showed higher glutathione (GSH) and Trolox equivalent antioxidant capacity (TEAC) (p=0.0445 and p=0.0360), respectively, compared with the I/I genotype. HU use was associated with a 35.2% decrease in the lipid peroxidation levels of the SCA (+HU) group (p<0.0001). Moreover, the SCA (+HU) group showed higher TEAC as compared to the control group (p=0.002). We did not find any significant difference in glutathione-S-transferase (GST) activity between the groups (p=0.76), but the catalase (CAT) activity was about 17% and 30% decreased in the SCA (+HU) and SCA (-HU) groups, respectively (p<0.00001). Whereas the plasma GSH levels were ~2 times higher in the SCA patients than the control group (p=0.0005). HU use has contributed to higher CAT activity and TEAC, and lower lipid peroxidation in patients under treatment. These findings may explain the influence of HU in ameliorating oxidative stress on SCA subjects.
authors.affiliation: UNESP-Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Genetic Diseases Laboratory, Sao Paulo, Brazil.
authors.forename: Danilo Grünig Humberto
authors.initials: DG
authors.lastname: Silva
authors.forename: Edis
authors.initials: E
authors.lastname: Belini Junior
authors.forename: Lidiane de Souza
authors.initials: Lde S
authors.lastname: Torres
authors.forename: Octávio
authors.initials: O
authors.lastname: Ricci Júnior
authors.forename: Clarisse de Castro
authors.initials: Cde C
authors.lastname: Lobo
authors.forename: Claudia Regina
authors.initials: CR
authors.lastname: Bonini-Domingos
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: de Almeida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D000986:Antisickling Agents / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D000986:Antisickling Agents; D006454:Hemoglobins; D005982:Glutathione Transferase; D006918:Hydroxyurea