Brain antioxidant activities of six artemisinin-based combination therapies (acts) in experimental malaria model

Thesis Abstract

Malaria parasite has remained a menace to human immune system as it usually subjects its host to oxidative stress which in turn has an effect on the levels of the antioxidant system due to generation of reactive oxygen species. This study investigated the brain antioxidant activities with six artemisinin-based combination therapies in an experimental malaria model. Forty (40) adult male Swiss albino mice between 20 – 30 g were randomized into 8 groups of 5 animals each. Groups 1 served as the normal control (NC) and were given normal feed and distilled water. Group 2positive control (PC) received 0.2ml of parasitized erythrocyte from a donor mouse. Group 3 was treated with 5.71 mg/kg body weight (ml/kg bw) Artesunate-amodiaquine – AA (CAMOSUNATE®) for 3 days, group 4 received 6.43 mg/kg bw Artesunate-mefloquine – AM (Artequin™) for 3 days, group 5 were given 2.86 mg/kgbw Artesunate-sulfadoxine-pyrimesthamine – ASP (SIMBCURE®) for 3 days, group 6 received 12.5 mg/kg bw Artemisinin-piperaquine – AP(ARTEQUICK®) for 2 days, group 7 received 5.14 mg/kg bw Dihydroartemisinin-piperaquine – DP (P-ALAXIN™) and group 8 received 8 mg/kg bw Artemether-lumefantrine – AL (Coartem®) for 3 days through oral administration after being inoculated with Plasmodium berghei strain intraperitoneally. The mice were then sacrificed by chloroform inhalation after treatment. The mice brain was harvested and the brain homogenates were used for antioxidant assay, also blood sample was obtained through cardiac puncture for parasite estimation. Result for parasitaemia level showed a significant decreased in groups 3, 4, 6, 7 and 8 in order of decreasing efficacy; AM > DP > AP > AA > AL > ASP. Implying the all the ACTs except ASP were efficacious in parasite clearance. AA, AM, AL and ASP groups had significant depleted levels of GSH, SOD, GPx and GST whereas CAT, MDA levels significantly increased with ASP, AP and DP when compared with NC groups. The vitamins showed variant results with the drugs as there were decreased levels of vitamin C in AP and DP groups while all the artesunate combinations elevated the levels of vitamins E and A. In conclusion the ACTs used suppressed the expression of most of the brain antioxidants even after parasite clearance, possibly due early onset of mice recovery from infection.

Keywords; Antioxidants, Artemisinin-based combination therapy, Brain, Malaria.