THE COMPARATIVE EFFECTS OF AQUEOUS AND ETHANOL FRUIT EXTRACTS OF PHOENIX DACTYLIFERA ON THE HIPPOCAMPUS AND CEREBELLAR CORTEX OF ARTESUNATE-AMODIAQUINE TREATED ADULT WISTAR RATS
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ABSTRACT
Amidst the current rise in the usage of artemisinin-based combination therapies as the first line treatment of falciparum resistant malaria in the Tropics, artesunate-amodiaquine combination therapy have been found to have degenerative and toxicity effects. This study was aimed at evaluating the effects of aqueous and ethanol fruit extracts of Phoenix dactylifera on the hippocampus and cerebellar cortex of artesunate-amodiaquine (AS-AQ) treated Wistar rats, as well as its effects on neurobehaviour, neuro-trace elements and oxidative stress markers. Thirty six (36) adult Wistar rats (150-180g) were used; they were randomly divided into nine groups. The rats in Group 1 served as the control; Group 2 was administered 2.86/ 8.75mg/kg AS-AQ. Groups 3, 4 and 5 were administered 2.86/8.75mg/kg AS-AQ + 500mg/kg aqueous extract of P. dactylifera (AEPD), 2.86/8.75mg/kg AS-AQ + 1000mg/kg AEPD and 2.86/8.75mg/kg AS-AQ + 1500mg/kg AEPD respectively. Groups 6, 7 and 8 were administered 2.86/8.75mg/kg AS-AQ + 500mg/kg ethanol extract of P. dactylifera (EEPD), 2.86/8.75mg/kg AS-AQ + 1000mg/kg EEPD and 2.86/8.75mg/kg AS-AQ + 1500mg/kg EEPD respectively. Group 9 served as the standard drug group and was administered 2.86/8.75mg/kg AS-AQ + 100mg/kg ascorbic acid. Once weekly, for 3 weeks, behavioural tests using the Morris water maze for spatial learning and memory, and Beam walk test setup for coordination and balancing were carried out. The drugs administration lasted for 28 days after which the animals were sacrificed, their brain excised and processed for histological (using Hematoxylin and Eosin, Cresyl fast violet, and Bielschowsky stains), biochemical (Superoxide dismutase, Catalase, Glutathione reductase, and Malondialdehyde), and neuro-trace elements (Zinc, Iron, Copper, and Manganese) studies. The histoarchitecture of the AEPD and EEPD treated groups were preserved particularly the 1000mg/kg and 1500 mg/kg doses, when compared to the AS-AQ and ascorbic acid treatments. The AS-AQ had no significant effect on the spatial learning and memory, and motor coordination and balance evidenced by the time latencies observed in the neurobehavioural study. Neurotoxicity, evidenced by necrosis, chromatolysis, vacuolations, was observed in the cerebellar cortex and hippocampus of the AS-AQ treated group. In the biochemical study, oxidative stress markers (SOD, CAT, and GSH) revealed no difference, while MDA concentration was significantly elevated (p<0.05) in the AS-AQ treatment when compared to the control. The neuro-trace elements result of trace metals (Zn, Fe, Cu and Mn) showed only Mn to have decreased significantly in the 1500mg/kg AEPD treated group. It was concluded that the ix amelioration of the severity of neurodegeneration, stability of the neurobehavioural index, alteration of oxidative stress markers and neuro-trace elements by the extracts indicated their ameliorative effects by antioxidant activities ascribed to the phytochemicals present in the extracts.
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