In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells

Abstract

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.

Resveratrol in Cancer Patients: From Bench to Bedside

“…ROS are a cornerstone in cancer onset and progression through the promotion of cell growth, immortalization and aberrant inhibition of locomotion and proliferation [143]. Resveratrol carries out its antioxidant properties through several mechanisms [143,144]. Especially, resveratrol modulates antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase [144].…”

“…Resveratrol carries out its antioxidant properties through several mechanisms [143,144]. Especially, resveratrol modulates antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase [144]. Therefore, it induces cancer cell apoptosis by accumulation of hydrogen peroxide [144].…”

“…Especially, resveratrol modulates antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase [144]. Therefore, it induces cancer cell apoptosis by accumulation of hydrogen peroxide [144]. Resveratrol can also downregulate hypoxia-inducible factor-1α (HIF-1α) accumulation, leading to the suppression of fluorodeoxyglucose (F-FDG) uptake from metabolically active cells and glycolysis [54,145].…”

In vitro and in vivo assessment of genotoxic activity of Petiveria alliacea

“…Peripheral human blood samples were obtained from healthy volunteers (non-smoking and non-drinking males and females between 20 and 45 years old) after approval by the Research Ethics Committee of UFPA (CAEE 0154.0.073.000-11, Registry 165/11 CEP-ICS/UFPA). The blood samples were obtained as previously described by Albuquerque et al (2015) for lymphocyte culture. In brief, 0.3 ml of venous blood were added to 4 ml of RPMI-1640 medium containing 20% of Fetal bovine solution (FBS) and 50 μg/ml phytohemagglutinin (PHA) to stimulate lymphocyte proliferation.…”

Mecanismos Moleculares De Ação Antioxidante De Vias Celulares Intrínsecas E Do Resveratrol

“…Em linfócitos e eritrócitos humanos, o Res inibiu os danos no DNA, bem como a formação de ROS pela atividade da enzima CAT. Com isso, o pré-tratamento com Res durante a terapia com DDS pode diminuir a oxidação de ferro heme e os danos no DNA pela redução da produção de ROS, mas não reverte completamente a formação da metahemoglobinemia, como observado no tratamento com azul de metileno (MET) (ALBUQUERQUE et al, 2015).…”