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Qinghaosu-mediated oxidation in normal and abnormal erythrocytes
M D Scott1, S R Meshnick, R A Williams
1Children's Hospital Oakland Research Institute, CA 94609.
The Journal of Laboratory and Clinical Medicine
|October 1, 1989
Summary
Qinghaosu enhances red blood cell (RBC) oxidation, particularly in oxidant-sensitive cells like those with sickle cell disease. This antimalarial drug increases RBC lysis and methemoglobin while decreasing glutathione, confirming its oxidative mechanism of action.
Area of Science:
- Biochemistry
- Hematology
- Pharmacology
Background:
- Qinghaosu is a potent antimalarial drug.
- Its mechanism of action is proposed to involve oxidative stress.
Purpose of the Study:
- To investigate the effects of qinghaosu on cellular oxidation in normal and oxidant-sensitive red blood cells (RBCs).
- To determine if qinghaosu acts as a prooxidant in RBCs.
Main Methods:
- Red blood cells (RBCs) with varying hemoglobin types (AA, SS, AE, EE) were treated with qinghaosu at different concentrations.
- Cellular deformability, lysis, methemoglobin generation, reduced glutathione concentration, and fatty acid composition were measured.
- Deoxyqinghaosu, an inactive analog, was used as a control.
Main Results:
- Qinghaosu altered RBC deformability at high concentrations (500 µmol/L).
- At lower concentrations (≤200 µmol/L), qinghaosu acted as a prooxidant, increasing susceptibility to oxidant-induced deformability loss.
- Oxidant-sensitive RBCs (SS, EE) showed more rapid deformability loss after qinghaosu treatment.
- Qinghaosu increased RBC lysis and methemoglobin generation, decreased reduced glutathione, and reduced unsaturated fatty acids in a dose-dependent manner.
- Deoxyqinghaosu had no significant effects.
Conclusions:
- The results confirm that qinghaosu exerts its effects via oxidative mechanisms.
- Qinghaosu-mediated oxidation is significantly enhanced in erythrocytes with inherent oxidant sensitivity due to unstable hemoglobins.
- These oxidative effects on uninfected erythrocytes occur at concentrations higher than those required for antimalarial activity.