Sub-acute evaluation of artesunate, amodiaquine and their combination on muscular coordination and morphology of the cerebellum of Wistar rats

Abstract

Artemisinin Combination Therapy (ACT) is currently the best choice for the treatment of malaria. Artesunate-amodiaquine combination is one of the most commonly used ACTs in Nigeria with a very potent efficacy but not without side effects involving motor coordination. Currently, there is dearth of information on its sub-acute effect on the cerebellum. This study investigated the sub-acute effects of artesunate (AS), amodiaquine (AQ) and artesunate + amodiaquine combination (AS+AQ) on the motor coordination, oxidative markers and morphology of the cerebellum of adult Wistar rats. Forty adult male Wistar rats were randomly divided into 4 groups, n=10. The rats were administered orally for 3 days, distilled water (control, CT), 4 mg/kg body weight AS, 10 mg/kg body weight AQ and 4 mg/kg AS + 10 mg/kg AQ. Rats were weighed, assessed for motor coordination and sacrificed on day 15. Brain tissues were excised and some cerebella preserved for oxidative stress and antioxidants while others were fixed in 10% NBF for histological and immunohistochemical studies. Results showed significant decreased body weight of the AQ group compared to the CT; decreased time of fore limb grip in the AS and AQ groups compared with the CT. Test groups showed increased LPO and NO, and lower levels of SOD, CAT and GSH compared with the control. Artesunate and AQ had significantly reduced number of Purkinje cells, AQ and AS caused increased astrocyte population and increased expression of iNOS. Sub-acute studies of Wistar rats treated with artesunate, amodiaquine and their  combination induced oxidative stress, reduced their motor function and impaired morphology of the cerebellum.

Keywords: Artesunate, amodiaquine, behaviour, cerebellum, histology, immunohistochemistry.