Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats
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Original Research
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Background: Hemolysis is common in malaria infection and during the course of
treatment. Previous studies have reported delayed post-artemisinin hemolysis occurring
in naïve and immune individuals treated with parenteral or oral artemisinin-derivatives.
This study aims to understand if delayed hemolysis occurs in the absence of malaria
parasites and the underlying mechanisms for the hemolytic effects after administration of
two antimalarial drugs to malaria-free Wistar rats. Methods: Forty animals were
randomized into 5 groups of eight animals each; they received 4 mg/kg artesunate for 7
days (AS), 4 mg/kg artesunate plus 10mg/kg amodiaquine for 3 days (ASQ), 10mg/kg
amodiaquine for 3 days (AQ), distilled water [normal control], (Control) and 1mg/kg
phenylhydrazine for 1 day to induce hemolysis (PHZ) groups respectively. Packed cell
volume (PCV), white blood cell differential count and serum haptoglobin (Hpt) levels
were determined in all groups on day 4 and 18 to detect hemolysis. Mean values were
compared using t-test and ANOVA with p values < 0.05 taken to be significantly
different. Results: Post-treatment mean PCV on day 4 was significantly lower than day
18 in all groups except AS group which had similar PCV all through evaluation. Although
AQ had lowest mean PCV on day 4, by day 18, mean PCV returned to normal and hpt
levels was significantly higher than AS and ASQ groups (p < 0.001). Hpt level (mean ±
sem) for AS, ASQ, AQ, and control on day 18 were: 18.67 ± 0.004, 50.66 ± 0.014, 73.06
± 0.003, and 74.13 ± 0.032 mg/dl respectively (p < 0.0001). On day 18, AS and ASQ
had significantly lower Hpt level compared to day 4 (p < 0.001). No neutropenia was
observed during the study. Conclusion: Artesunate induces delayed hemolysis in
malaria-free animals possibly through an oxidative toxic effect on the red blood cell
membrane. Delayed post-treatment hemolysis was not observed with artesunateamodiaquine
or amodiaquine alone.
Keywords
QD Chemistry, QH301 Biology