EFFECTS OF CO-ADMINISTRATION OF PROMETHAZINE AND ARTEMETHER-LUMEFANTRINE IN PLASMODIUM berghei berghei INFECTED MICE
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ABSTRACT
Malaria is the 2nd leading cause of death from infectious diseases in Africa, after HIV/AIDS. It is a major public health problem in Nigeria where it accounts for most cases of hospital visits and deaths than any other country in the world. This study evaluated the effects of coadministration of promethazine and Artemether-Lumenfantrine in mice infected with Plasmodium berghei berghei. The mice were grouped into six groups of 6 mice each. Group 2 – 6 were inoculated with Plasmodium berghei berghei groups. Drug administration was carried out orally and for 5 days, 72 hours after parasite inoculation and parasitaemia seen. The mice were sacrificed on the 8th day. Blood samples were collected and organs harvested for haematological and histopathological evaluations. Parameters evaluated include average parasitaemia inhibition, haematological indices, organ-body weight ratio and liver transaminases. The liver, kidney and heart were subjected to histological evaluation. The result showed that promethazine alone had no significant parasitaemia inhibition but the coadministration of promethazine (both 25 mg/kg and 50 mg/kg) and artemether-lumenfantrine gave a marginal reduction but not a significant one compared to Artemether-lumenfantrine alone. Promethazine showed a significant reduction in Haemoglobin, Pack cell volume, RBC, and increase in neutrophils compared to Artemether-Lumenfantrine alone, but no effects compared to the infected control. Its co-administration of promethazine (25 mg/kg) with Artemether-Lumenfantrine gave a marginal reduction, but not a significant difference in Hb, PCV and RBC. The 50mg/kg dose of promethazine co-administered with artemetherlumenfantrine gave lower values of PVC, Hb, RBC than the 25mg/kg promethazine dose plus artemether-lumenfantrine. The liver transaminases were significantly (p≤0.05) increased for Promethazine co-administered with artemether-lumenfantrine compared to Artemtherlumenfantrine alone, although the values of AST, ALT and ALP were still mostly within the normal ranges ( AST-20-298U/l, ALT-17-80U/l, ALP-30-110U/l). Histology sections of the liver showed slight increase in hepatic congestion and lymphocyte hyperplasia, renal sections showed no significant changes while the heart sections showed slight lymphocyte hyperplasia. The study showed that co-administration of Promethazine and Artemether-lumenfantrine possesses no advantage over Artemether-Lumenfantrine alone and it has tendencies of toxicity with continuous use.
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