Effects Of Chronic Administration Of Nifedipine On The Reproductive System Of Wistar Rats

Nifedipine, one of the antihypertensive drugs is associated with various side effects on organs of the body but there is paucity of information on its effects on female reproductive system of Wistar rats. The study evaluated the effects of Nifedipine on the female reproductive system. The objectives of the study were to: (i) investigate the effect of Nifedipine on the oestrous cycle of the non – pregnant Wistar rats; (ii) determine the effect of Nifedipine on the serum levels of oestradiol, progesterone, and gonadotrophins in non - pregnant and pregnant Wistar rats; (iii) investigate the effect of Nifedipine on the foetuses at term; and (iv) demonstrate any histoarchitectural changes in the ovary of the treated animals.rnrnThe study was carried out in two experimental stages: in the first stage, eighteen cycling non-pregnant Wistar rats were used. They were divided into three groups with each group comprising six rats. Rats in group I were administered 10 ml/kg body weight of distilled water (control), group II was administered aqueous solution of Nifedipine 1.5mg/kg body weight, while rats in group III were administered 3 mg/kg body weight. In the second stage, eighteen pregnant Wistar rats were used. They were grouped and treated as the cycling non-pregnant Wistar rats. Doses of distilled water and the drug solutions were delivered orogastrically once daily for 21 days. Vaginal smears cytology was done daily throughout the 21 days in the non-pregnant rats and the cell types recorded. All the medications were administered through the orogastric route. At the end of the experiment, the rats were euthanized using 20 mg/kg body weight of ketamine hydrochloride. Whole body perfusion fixation was done using 4% paraformaldehyde. Blood specimens were taken for evaluation of sex hormones. The ovaries were removed and fixed in 4% paraformaldehyde solution before tissue processing. In the pregnant groups, the pup-containing uteri were similarly harvested for morphological evaluation. Data were analysed using Student’s t-test at 0.05 level of significance.rnThe findings of the study were that:rn(i) there was total disruption of the oestrous cycles in Nifedipine treated in both the low and high-doses compared with the controls; rn(ii) the serum levels of oestradiol was 41.0 ± 6.14 pgm/ml for the control, 75.83 ± 12.61 pgm/ml for non-pregnant and 2036.0 ± 50.57 pgm/ml for the pregnant rats;rn(iii) luteinizing hormone concentration was 13.6 ± 5.51 mIU for non-pregnant, 5.9 ± 0.64 mIU for the pregnant and 9.48 ± 1.45 mIU for the control; rn(iv) the serum levels of progesterone was 26.2 ± 2.33 ng/ml in non-pregnant rats, 98.4 ± 1.47 ng/ml in pregnant and 24.2 ± 0.96 ng/ml in the control;rn (v) there were no obvious congenital malformation affecting the foetuses; andrn (vi) there was loss of cortico-medullary demarcation in the treated groups.rnThe study concluded that there were structural ovarian changes associated with use of Nifedipine in Wistar rats. The study recommended that Nifedipine should be avoided in rncontrol especially in non-pregnant individuals.

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