The aim of the present study was to conduct a preliminary screen of neem, a valuable plant source commonly used in traditional medicine and in modern drug development, to determine its potential for reproductive toxicity. Neem bark extract at dose 50, 100 and 300 mg/kg bodyweight was administered by gavage to pregnant rats daily from gestational day 1 to 20. Implantation rate, fetal mortality, fetal body weight and length, external and skeletal abnormalities, micronucleus assay in fetal liver cells, as well as histological and ultrastructural examination of fetal liver, were studied. On the other hand, maternal body weight, absolute and relative organs weight, micronucleus assay in bone marrow, histological and cytological examination of liver, and certain parameters related to liver function (serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities, as well as total protein, albumin and globulin content) were determined in mothers. No effects were observed on reproductive outcomes or dams received dose of 50 or 100 mg/kg body weight, except some histological and cytological liver defects were observed at 100 mg/kg body weight. Neem bark extract administered at dose 300 mg/kg body weight was associated with reduced fetal body weight, minor skeletal variations, and moderate histological and ultrastructural alterations in the liver. However, no considerable adverse effect on implantation, mortality rate, external malformation, or in frequency of micronucleated polychromatic erythrocytes in fetal liver cells was observed. In dams exposed to the high dose, significant physiological, histological and cytological alterations in liver were observed without affecting body weight, organs weight, or bone marrow micronuclei rate. In conclusion, neem bark extract was not teratogenic or genotoxic in rats. It has a low potential to adversely affect prenatal development only at maternally toxic dose.
Read full abstract