EFFECTS OF ANTIMALARIAL DRUGS ON OESTROUS CYCLE AND UTERINE CONTRACTILITY IN RATS

EFFECTS OF ANTIMALARIAL DRUGS ON OESTROUS CYCLE AND UTERINE CONTRACTILITY IN RATS

ABSTRACT

Malaria is increasingly a health burden globally with children under the age of 5 and pregnant women being the most vulnerable. Several antimalarials are available in the market today however; the safety data in pregnancy is inadequate especially the first trimester of pregnancy. The study was carried out in both pregnant and non-pregnant wistar rats to evaluate the effect of these antimalarial drugs on the oestrous cycle as well as on the uterine smooth muscle contractility. All the antimalarial drugs in this study (AT 3.2 mg/kg loading dose and 1.6 mg/kg maintenance dose for 7 days; CQ 2.5 mg/kg every 4 hours; QN 20 mg/kg loading dose and 10 mg/kg maintenance dose 8 hourly for 7 days and SP 25 mg/1.25 mg/kg once); showed a desynchronization of the normal oestrous cycle. Proestrus phase was increased by all the antimalarial drugs except for AT, oestrus phase was decreased by all but significantly by QN and metoestrus was increased by all except SP which decreased it significantly while the dioestrus phase, a decrease was observed. On isolated uterine smooth muscle of pregnant rat, artemether (AT, 16 µg/ml – 1280 µg/ml) Chloroquine (CQ, 4 mg/ml – 32 mg/ml), quinine (QN 100 ng/ml – 800 ng/ml) and sulphadoxine /pyrimethamine (SP, 100 µg/ml – 400 µg/ml ), had no agonist effect on the uterus but AT (16 µg/ml – 1280 µg/ml), CQ (16 mg/ml) and SP (100 µg/ml) produced a reduction in oxytocin induced contraction of the pregnant uterus. In conclusion, this study showed that these antimalarial drugs caused a desynchronization of the normal oestrous cycle suggesting a possible effect on the menstrual cycle in women of child bearing age while the reduction in the oxytocin induced contraction could translate to ill effect especially in late pregnancy and during labour.

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