Teratogenic Effects of Carissa spinarum and Azadirachta indica Aqueous Extracts in Mice

Carissa spinarum (mũkawa in Kikuyu, lamuriak in Maasai) and Azadirachta indica (neem, mwarubaini in Kiswahili) are widely used in African communities. C. spinarum is used as food and as treatment for gonorrhoea, cancer, and abnormal pain in pregnancy. A. indica is used as a mosquito-repellent and as treatment for malaria and dental carries. Both plants have broad biological activities including anticancer, hypoglycaemic, antinociceptive, and anti-inflammatory activity. However, data on their safety for use during pregnancy is scarce. This study aimed to determine the teratogenic effects of C. spinarum and A. indica in mice. FDA guidelines for reproduction studies were used. Pregnant mice were randomly divided into 8 groups (n=5) for the assay. Plant extracts were prepared in the doses 100, 250, and 500mg/kg body weight. Phenytoin sodium 100mg/kg body weight was used as the positive control and distilled water was used as the negative control. Treatments were administered orally and began from gestation day 6 and ended on gestation day 15. On gestation day 18, the mice were weighed and euthanized and the pups were recovered. Weights of the gravid uteri, number of pups and their body measurements, and incidences of foetal resorption were also recorded. Data were expressed as means and their standard errors and analysed using one-way ANOVA/Dunnett’s post hoc test. The significance level was set at p<0.05. Heavy metal concentrations in the plant samples were determined using flame photometry and atomic absorption spectrophotometry. All doses of C. spinarum and A. indica caused significant (p<0.001) weight loss and foetal resorption in the gravid mice. Reduced head sizes (microcephaly) and elongated limbs were observed in the C. spinarum 100mg/kg and A. indica 500mg/kg groups. Premature birth and high birth weights were also observed in the latter group. The plant samples were found to have high concentrations of lead, cadmium, iron, chromium, manganese, and zinc and this may have added to the teratogenicity observed. C. spinarum and A. indica exhibited significant teratogenicity and should be used with caution during pregnancy. In addition, the level of heavy metal contamination in Kenya should be assessed.