In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.
Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDS-NHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.
Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, 66075-110, Belém, PA, Brasil.
Rosyana V
RV
Albuquerque
Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Belém, Pará, Brasil.
Nívea S
NS
Malcher
Instituto de Ciências Biológicas, Universidade Federal do Pará/UFPA, Belém, PA, Brasil.
Lílian L
LL
Amado
Mechanisms of Drug Toxicity Group, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, United Kingdom.
Michael D
MD
Coleman
Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Belém, Pará, Brasil.
Danielle C
DC
Dos Santos
Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, 66075-110, Belém, PA, Brasil.
Rosivaldo Sa
RS
Borges
Seção de Parasitologia, Instituto Evandro Chagas, SVS, MS, Pará, Brazil.
Sebastião Aldo S
SA
Valente
Seção de Parasitologia, Instituto Evandro Chagas, SVS, MS, Pará, Brazil.
Vera C
VC
Valente
Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, 66075-110, Belém, PA, Brasil.
Marta Chagas
MC
Monteiro
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003622:Dapsone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D008708:Methemoglobinemia / Q000188:drug therapy / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
D000975:Antioxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D003622:Dapsone; D008706:Methemoglobin; D002374:Catalase; D013482:Superoxide Dismutase; C018209:4-amino-4'-hydroxylaminodiphenylsulfone; D000077185:Resveratrol