Imatinib mesylate, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukemia and gastrointestinal stromal tumors. The aim of the present study is to investigate the effects of imatinib mesylate on the pregnant rats and their fetuses. Pregnant rats were divided into three groups; the first group served as a control group. The second and third groups were orally administered imatinib at doses of 36 mg/kg body weight or 54 mg/kg b.wt. on gestation days (SDs) 6 through 13 or SDs 13 through 19, respectively. All animals were sacrificed on the 20th day of gestation. Treatment with imatinib caused a reduction of maternal body weight gain, uterine and placental weights, increased rate of abortion and fetal resorptions. High dose of imatinib caused fetal congenital deformities represented in harelip, contraction of the fore limbs, and paralysis of the hind limbs, exencephaly, encephalocoele and distended abdominal wall, besides occurrence of wavy ribs and absence of other ribs in addition to skeletal growth retardation and lack of ossification of the most skeletal elements. The present work concluded that imatinib is teratogenic when given orally to pregnant rats at 54 mg/kg b.wt. and causes direct maternal or developmental toxicity.

W e investigated the digitalis like potentialities of judaicin in rats. Both the pharmacologic and the toxic actions of jtzdaicin and digoxin were studied in respect to the cardiac response. The pharmacological action as well as the cardiotoxic action of both drugs were electrocardiographically parallel. Both drugs caused a prolongation in the P-R interval and enforcement of the cardiac contractility.Further investigations are required for completing the picture of the pharmacological action of judaicin.For many years, Artemisia judaica L. (Compositae), Arabic name ,,ShihBalady", has enjoyed a wide reputation among herb-experts in Egypt for its usefulness as a medicinal herb. Judaicin, a crystalline bitter principle, m. p. 178' C, was isolated by KHAFAGY (1954) as a new sesquiterpene lactone from Artemisia jzidaica (yield 2%). KHAFACY (1956) on the basis of preliminary chemical charac-' terisation of judaicin suggested the molecular formula I, which was later modified by SABER et a1 (1964) to formula 11. GALAL et al. (1968) subjected judaicin to an array of pharmacological studies. I t was found to cause a significant slowing of the heart rate and was well tolerated by the isolated mammalian heart. Large doses of 15 mg reduced the amplitude of cardiac contraction by one third. O n the other hand, the coronary outflow was conspicuously increased. The pharmacological investigations revealed also a paraDownloaded by: National University of Singapore. Copyrighted material.

The present study was conducted to investigate the potential adverse effect of Pb on pregnant Sprague–Dawley rats and their fetuses after maternal exposure, on gestational days (GD) 7–16. The possible protective role of taurine (TA), administered throughout the gestation period (GD 1–20) against Pb toxicity, was also evaluated. Pregnant rats were divided into four groups: Group 1 (control) was given distilled water; Group 2 was exposed to Pb (250 ppm) in drinking water (GD 7–16), whereas Group 3 received TA (50 mg/kg/day) by oral gavage (GD 1–20); Group 4 was exposed to Pb (GD 7–16), whereas pretreated with TA from GD 1 till the end of the gestation period. After termination on GD 20, maternal and embryo‐fetal outcomes were evaluated. Blood samples were collected for hematological and biochemical parameters assessment. The results showed that, Pb induced a significant reduction in the maternal body weight, weight gain, uterine and placental weight, in addition to a high incidence of abortion and fetal resorption. Meanwhile, fetuses demonstrated decreased body weight and length, with a high rate of mortality as well as external and skeletal abnormalities. Additionally, Pb induced severe hematological and biochemical alterations in both dams and fetuses. The toxicity of Pb was further emphasized by placental histopathological examination and hepatic DNA fragmentation. Pretreatment with TA greatly attenuated the impact of Pb on both maternal and fetal parameters. Moreover, TA alleviated the incidence of placental damage and hepatic DNA fragmentation. The results highlight the potential prophylaxis role of TA against maternal and developmental Pb toxicity.

No abstract

Cadmium is a potent teratogen in laboratory animals, causing exencephaly when administered at early stages of development. Due to its heterogenicity with respect to molecular targets, the mechanisms behind cadmium toxicity are not well understood. In the present study, 40 pregnant rats (Sprague-Dawley) were divided into four groups (10 each); first group served as the control (G1), the second group (G2) received 61.3 mg/kg cadmium chloride daily from 7th to 16th day of gestation (organogenesis period) by oral tube. Group 3 (G3) was administrated a solution of 25 mg/kg zinc chloride orally from the 1st day to 20th day of pregnancy. Group 4 were administrated a solution of cadmium chloride (61.3 mg/kg) and zinc chloride (25 mg /kg) daily from the 7th to16th day of gestation. Maternal body weights were measured on gestational day 0, 6, 9, 12, 15 and 20. At the 20th day of gestation, blood samples were collected from the eye, using orbital sinus technique. Serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined calorimetrically and serum, urea and creatinine were determined. All of the pregnant rats were sacrificed by ether anaesthesia at the 20 th day of gestation and foetuses were removed from the uterus. The implantation sites, corpora lutea, living, dead and reabsorbed foetuses were counted and recorded. Liver of pregnant rats and their fetuses were used to isolate a total RNA for quantification of Msx1, Cx43, Bcl2 and Bax genes. The results show the toxic effect of Cd on the pregnant rats and their fetuses, at morphological, physiological and molecular level but, zinc has a very effective protection against cadmium-induced developmental toxicity.