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Fig 1.

Effect of the DDS-NHOH on methemoglobin formation in human erythrocytes.

Erythrocytes were incubated with different concentrations of DDS-NHOH (2.5; 5.0 and 7.5 μg/mL) for 1 h at 37°C. Data are reported as means ± S.E.M from three independent experiments done in triplicate. *P < 0.05 compared to methanol group.

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Fig 1 Expand

Fig 2.

Effect of the pretreatment with different concentration of resveratrol (RSV) on methemoglobin formation induced by DDS-NHOH.

Erythrocytes were pretreated with different concentrations of RSV(10, 100, 200 and 1000 μM) for 1 h at 37°C, then these cells were incubated with different concentrations of DDS-NHOH (2.5; 5.0 and 7.5 μg/mL) for 1 h at 37°C. Data are reported as means ± S.E.M from three independent experiments done in triplicate. #P < 0.05 compared to DDS-NHOH group.

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Fig 2 Expand

Fig 3.

Comparative effect of the pretreatment with resveratrol (RSV) or methylene blue (MET) on methemoglobin formation induced by DDS-NHOH.

Erythrocytes were pre-incubated with RSV (100 μM) for 1 h or MET (40 nM) for 30 min, after these cells were incubated for 1 h with different concentrations of DDS-NHOH (2.5, 5.0 and 7,5 μg/mL). Data are reported as mean ± S.E.M. #P < 0.05 compared to DDS-NHOH group.**P < 0.05 compared to resveratrol group.

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Fig 3 Expand

Fig 4.

Comparative effect of post-treatment with resveratrol (RSV) or methylene blue (MET) on methemoglobin formation induced by DDS-NHOH.

Erythrocytes were incubated for 1 h with DDS-NHOH (2.5 μg/mL), then these cells were incubated with RSV (100μM) for 1 h or MET(40 nM). Data are reported as mean ± S.E.M. *P < 0.05 compared to methanol group. #P < 0.05 compared to DDS-NHOH group.

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Fig 4 Expand

Fig 5.

Effect of treatment with resveratrol on DNA damage induced by DDS-NHOH.

Tail Length (μm—A), DNA in tail (%—B) Tail Moment (TM—C) and Olive Moment (OM—D) were used as a marker of DNA damage in lymphocyte using Comet assay. As positive control was used H2O2 (200 μM). All values are depicted as mean ± S.E.M.

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Fig 5 Expand

Fig 6.

Reactive oxygen species (ROS) generation.

Erythrocytes were pretreated with resveratrol (RSV, 100 μM and 1000 μM) for 1 h at 37°C and incubated for 30 min with DDS-NHOH (2.5 μg/ml and 7.5 μg/ml). As positive control was used T-BHP (200 μM). ROS production was measured as dichlorofluorescein (DCF) fluorescence. Values are means ± S.E.M. *P < 0.05 compared to methanol group. #P < 0.05 compared to DDS-NHOH group.

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Fig 6 Expand

Fig 7.

CAT and SOD activity.

Erythrocytes were pretreated with resveratrol (RSV, 100 μM and 1000 μM) for 1 h at 37°C and incubated for 30 min with DDS-NHOH (2.5 μg/ml) or T-BHP (200 μM). Results are expressed as mean ± S.E.M. *P < 0.05 compared to methanol group.

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Fig 7 Expand

Fig 8.

HOMO surface.

Structure for HOMO of the dapsone hydroxylamine (DDS-NHOH), resveratrol (RSV), and methylene blue (MET). All nodal patterns related to individual group contributions are presented by blue or yellow for negative or positive wave function, respectively.

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Fig 8 Expand

Table 1.

Theoretical parameters for redox mechanism.

HOMO, LUMO, GAP, Ionization potential (IP) and stabilization energy (ΔEiso) of DDS hydroxylamine (DDS-NHOH), resveratrol (RSV), and methylene blue (MET). All values are given in eV.

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Table 1 Expand

Fig 9.

Redox mechanism.

Ionization potential and stabilization energy of dapsone hydroxylamine (DDS-NHOH), resveratrol (RSV), and methylene blue (MET) on antioxidant and methemoglobinemia reversion.

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Fig 9 Expand

Fig 10.

Proposal for a possible action mechanism of resveratrol (RSV) in inhibiting methemoglobin formation and DNA damage induced by DDS hydroxylamine (DDS-NHOH) in vitro model.

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Fig 10 Expand