Artesunate-induced hemolysis and hypoglycemia in rats: Gender implication and role of antioxidant enzymes

Abstract

Introduction: The gender implication of the effects of artesunate on hematological parameters and blood glucose is not well understood. The present study investigated the effects of artesunate on some hematological parameters, blood glucose, and antioxidant enzymes in both the sexes. Materials And Methods: A total of 35 male and 35 female Wistar rats were randomly divided into five groups (n = 7). Group one rats received distilled water; groups two and three received 2.90 mg/kg artesunate on the first day and 1.45 mg/kg artesunate from the second day until the fifth and fifteenth days, respectively; and groups four and five received 8.70 mg/kg artesunate on the first day and 4.35 mg/kg artesunate from the second day until the fifth and fifteenth days, respectively. Results: The results of this study showed that an increase in G-6-PD activity alone prevented hemolysis in the male, but not in the female rats following a short duration of treatment. However, after a longer duration of treatment, a synergy between gucose-6-phosphate dehydrogenase (G-6-PD) and catalase prevented hemolysis in the female rats, whereas hemolysis occurred in the male rats due to the absence of an increased G-6-PD activity. Probably due to hormonal differences, artesunate reduced fasting blood glucose in the females, but it was either hypoglycemic (at low dose) or hyperglycemic (at high dose) in the male rats. Discussion: In conclusion, the present study suggests that a duration-dependent difference exists in the onset of artesunate-induced hemolysis and the response of antioxidant enzymes in the male and female rats and that following longer duration of treatment, hypoglycemia could be sustained in the female rats while counterregulatory mechanism(s) could be triggered in the male rats.

Keywords

• Antioxidants
• artesunate
• free radicals
• hemolysis
• hypoglycemia