Separate and combined sub-acute effects of artesunate, amodiaquine on spatial memory and hippocampal morphology of adult Wistar rats

Abstract

We evaluated the sub-acute effect of artesunate (AS), amodiaquine (AQ) and AS plus AQ on the structure and function of the hippocampus of adult  Wistar rats. Forty adult male Wistar rats weighing between 110-215 g, were divided into 4 groups (n=10); group A-control (CT) rats administered  distilled water, group B-4 mg/kg, AS, group C-10 mg/kg, AQ and group D- 4 mg/kg, AS + 10 mg/kg, AQ body weight. Drugs were administered orally  for 3 days and neurobehavioral tests (Morris water maze) for spatial memory and cognition done from day 11 to 14. The rats were sacrificed on the  day 15 and blood sample collected for full blood count. The rat brain of all groups was excised, and the hippocampus dissected out, fixed in 10%  formol-saline and processed for histology and immunohistochemical (glial fibrillary acidic protein, GFAP (astrocytes) and inducible nitric oxide  synthase, iNOS (oxidative stress)) studies. Data were analysed by one-way ANOVA at p<0.05. Subacute evaluation showed that the AQ-treated rats had significantly increased swimming time and distance, red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb) and packed cell volume  (PCV) compared with the CT and other groups. Histologically, there was decreased Cornus Ammonis 1 (CA 1) pyramidal neurons in the hippocampus of the AS and AQ-treated rats compared with the CT group. Increased astrocyte population was observed in the hippocampus of AS and AQ groups compared with the CT and AS+AQ groups, as well as increased iNOS expressions compared with the CT group. Subacute evaluation of the adult rat hippocampus indicated that amodiaquine decreased spatial memory and increased blood cell counts, while artesunate and amodiaquine induced  oxidative stress resulting in pyknosis of and decreased pyramidal CA1 neurons and caused astrogliosis.