Screening study on the effect of Neem bark extract on pregnant rats and their fetuses.

Abstract

The aim of the present study was to conduct a preliminary screen of a valuable plant source (Neem) commonly used in traditional medicine and in modern drug development as well as pesticide manufacture to determine its potential for reproductive toxicity. Neems bark extract at doses 50, 100 or 300 mg/kg bwt. were administered by gavage to pregnant rats daily from gestational day (GD) 1 - 20. Implantation rate, fetal mortality, body weight and length, external and skeletal abnormalities, micronucleus assay (Mn) in embryonic liver cells as well as histological and ultrastructural examination of fetal liver were determined by Caesarean section on GD21. On the other hand, maternal body weight, absolute and relative organs weight, micronucleus assay in bone marrow, histological and cytological examination of liver as well as liver function (through measuring serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities as well as total protein, albumin, and globulin content) were determined. No effects were observed on reproductive outcomes or treated dams received 50 or 100 mg/kg bwt of Neem bark extract. Neem bark extract administered at dose 300 mg/kg bwt, was associated with reduced fetal weight, minor skeletal variations and moderate histological and ultrastructural alterations in liver. However, no considerable adverse effect on the embryonic implantation, mortality rate, external malformation or embryonic liver cells micronucleus was observed. Significant physiological, histological and cytological alterations in dams liver was observed without affecting body weight, organs weight, or bone marrow micronuclei rate in dams exposed to the high dose. In conclusion, Neem bark extract was not teratogenic or mutagenic in rats. It has a low potential to adversely affect prenatal development only in the highest dose used in the present study, i.e. at maternally toxic dose.