Dear Editor: Viruses and drugs are well-known teratogens. In 1941, rubella virus was shown to cause severe birth defects such as cataracts, deafness and cardiac defects. Thalidomide received worldwide attention in the 1950s, after over 10, 000 neonates were born with malformations1, 2.

Florfenicol is a broad-spectrum antibiotic that used in different diseases. There is no evidence for Teratogenicity effect of florfenicol; the aim of this study was to evaluate the teratogenic effect of florfenicol on skeletal system of rat fetuses. This study was performed on 39 pregnant rats in 5 groups, including first group (control group) and 2-5 groups (test groups) that was received florfenicol at doses 100, 200, 400 and 800 mg/kg, respectively. The drug was administrated at 8th and 10th days of gestation intraperitoneally. The rats were euthanized and fetuses were collected at 20th day of gestation prior to calculation of weight and length. Then, they were stained by alizarin red- alician blue method. The stained skeletal system of the fetuses were eviscerated and cleaned before they investigated by stereomicroscope. Fetus absorption rate in 1-5 groups were 4.09%, 22.64%, 44.68%, 53.58% and 59.32%. Skeletal teratogenicities consist of cleft palate, sternum malformation, reduce limbs ossification of hind limb and fore limb, observed in 4th group (400 mg/kg florfenicol) were 11.53, 11.53 and also 11.53% and in 5th group (800 mg/kg florfenicol) 20.38, 12.50 and 37.50%. It is concluded that, florfenicol produced some tratogenic skeletal disorders including cleft palate, sternum malformation; reduce limbs ossification and fetus absorption doses-depended in rat fetuses.

Diethylstilbestrol (DES) was widely used in the past, as the morning after contraception, but its application became extremely limited due to several complications including delayed clear cell adenocarcinoma in female infants.However, the use of DES increased during the past decade for hormone replacement therapy. The aim of this study was to investigate possible Teratogenicity of this synthetic oestrogen. The experiment was conducted on N-MRI mice. Various concentrations of DES were administered i.p. to pregnant animals throughout the period of organogenesis (days 9 and 10 of pregnancy). The control group received ethanol as vehicle. Pregnancy was terminated on the 18th day by cervical dislocation.The embryos were then removed and fixed in Bouin’s solution, and parameters currently used in teratogenic studies were assessed. Severe embryo toxicity score was observed following the application of DES at doses of 200 and 400 mg/kg (71.4% and 83.6%, respectively). The weight and the average size of some of the examined parameters were markedly decreased by embryological observation. Furthermore, the size of derm and mosaic cells of urinary bladder, shortening in the length of femur, and abnormal disposition of calcium compound in embryos were markedly different in the treated mice.

Background: It has been shown that Salvia leriifolia Benth. has various pharmacological effects such as anti-hyperglycemia, anti-inflammatory, analgesic, muscle relaxant and sedative effect. There is a considerable potential for usage of this plant during pregnancy. However, its effects on embryonic development have not been examined. Objective: In this study, the in vivo fetotoxicity of S. leriifolia aqueous and alcoholic extracts were evaluated in mice. Method: For this purpose, 10% and 30% of the maximal tolerated dose (MTD) of aqueous or alcoholic extracts were daily injected intraperitoneally in pregnant mice on GD=6 (Gestation Day) to GD=14. On GD=18, embryos were harvested by Cesarean section and then morphological structures and skeletal anomalies were evaluated. Other embryos were fixed and stained for bone and cartilage assessments.Results: Both doses of alcoholic and aqueous extracts caused significant decrease in weight gain of pregnant mice; length and weight of fetuses were also reduced remarkably compared to the control group. Alcoholic and aqueous extracts caused some abnormalities such as spina bifida, limb abnormalities, abdominal bleeding, and bone abnormalities. Conclusion: This study presents strong evidence that S. leriifolia can cause numerous embryotoxicities. Thus, pregnant women should be careful in using this herb during pregnancy and it is best to avoid its use until further studies are performed.

Background: Albendazole is utilized as an anthelmentic agent. One its side effect is Teratogenicity. This effect apparently is related to its metabolites especially albendazole sulfoxid. The aim of present study was evaluation effect of erythromycin (as enzyme inhibitor in biotransformation) on albendazole biotransformation and consequently fetal malformation.Materials and Methods: Four groups of female pregnant wistar rats (8 rats each group) were used. First group received normal saline (as control group). A single oral dose 30 mg/kg of albendazole was administered to rats on day 10 of gestation in group 2. Rats in group 3 received albendazole similar group 2 and erythromycin at dose 60 mg/kg. Rats in group 4 received only erythromycin on day 10 of gestation. The rats were euthanatized on day 20 of gestation. The skeletal malformation of fetus was studied by stereomicroscope after staining by Alizarin red-Alcian blue.Results: The length and weight of fetuses were significantly decreased by albendazole but erythromycin did not prevent this effect. In group that received only erythromycin, the length and weight of fetuses was similar to control group. Erythromycin decreased albendazole effect on weight of placenta. There was an increase in resorption by erythromycin when co-administrated with albendazole. The incidence of skeletal malformations (mostly of the limbs, vertebrae and palate) decreased significantly by erythromycin when co-administrated with albendazole.Conclusion: Thus, erythromycin may inhibit albendazole biotransformation and decrease Teratogenicity of it metabolites, but this subject needs more detailed evaluation.

Background: Furosemide as a loop diuretic can use in treatment of hypertension, renal or heart failures and cirrhosis, when sodium retention is significant. It is known that use of furosemide can be lead congenital abnormalities in humans and animals. Nitroprusside as a NO donor can decrease blood supply complications and constriction of placenta and uterus via vasodilation and improvment blood supply. The aim of this study was preventation or decrease of Teratogenicity form furosemide in rat fetuses by sodium nitroprusside.Materials and Methods: This study was performed on 28 pregnant rats that were divided into four groups, the groups consist control, furosemide, sodium nitroprusside and furosemide plus sodium nitroprusside. Drugs were administrated on 14th and 16th day of gestation. Test groups received furosemide (200mg/kg) orally, and nitroprusside (0.5 mg/kg) intraperitoneally. The rats were euthanized and fetuses were collected at 19th day of gestation, after weight and length determination, they stained by Alizarin red- Alician blue method. Then the skeletal system of the stained fetuses was investigated by stereomicroscope for Teratogenicity effects.Results: The results showed the cleft palate, wavy ribs and decreased ossification mean incidence in forelimbs and hindlimbs were 11.11%, 68.88% and 20% in the fetuses of the rats received furosemide, where as it decreased to 7.31%, 21.95% and 12.19% in group which received furosemide plus nitroprusside, respectively.Conclusion: It is concluded that sodium nitroprusside can significantly decrease Teratogenicity induced by furosemide.

The teratogenic effects of morphine sulfate exposure, during pregnancy, were studied in Balb/C mice, in three different concentrations of 0.01, 0.05 and 0.1 mg/ml, using oral administration. For addiction, the drug was provided in increasing concentrations for 3 weeks (n=26-63); one control and seven experimental groups, for every concentration were used, which included non-administered (untreated) and administered (treated) females mated with treated and untreated males. For the first time, cesarean sections were performed on the end of gestation; number of fetuses and resorption sites were recorded. Fetuses and placentas were examined externally and preserved for subsequent visceral and skeletal examinations. Fetal morphine sulfate exposure was associated with significant reduction in size of litters (P<0.05) weight (P<0.001), length of crown-rump (P<0.001, P<0.005) and placenta weight (P<0.001), P<0.005) and diameter (P<0.001), in two doses of 0.01 and 0.05 mg/ml. With using 0.1 mg/ml, only some experimental groups showed significant decrease (P<0.05). All exposed-groups showed an increase in the percentage of abnormalities compared to control groups (P<0.001). Staining the skeletal structures showed an extra rib in fetuses. Results revealed that morphine possess: 1) teratogenic potential on developing mice fetuses, in doses of 0.01, 0.05 and 0.1 mg/ml; 2) male-exposure to morphine has lower disruptive effects on embryos than female exposure, and 3) teratogenic effects of morphine increase with lower doses.

Enamel matrix derivative Emdogain (EMD) is widely used in periodontal treatment in spite of the fact that its effect on the developing embryo has not been elucidated. The aim of this study was to investigate the teratogenic effect of EMD on the rat embryo neural crest cells. The neural crest is a unique population of cells that migrates from the dorsal neural tube along defined pathways and produces various cell types including the melanocytes, neuronal and glial cells of the sensory, autonomic and enteric nervous system as well as the chromaffin cells of the adrenal gland. These cells have been used extensively for in-vitro studies of neurogenesis. Cultured cells by micromass culture method derived from midbrain of six embryos (13 day postcoitum; 34-36 smites) and exposed to various concentrations of EMD for 5 days at 37°C and differentiated foci were counted. Retinoic Acid (20 mg/mL) was used as standard positive control. These cells were stained using Mayer’s hematoxylin which is specific for staining differentiated cell nucleus. Neutral red staining determines cell viability rather than related cell differentiation but is used for normalization of Mayer’s hematoxylin results. At the concentration as low as 8 mg/mL of EMD, no toxic effect on fetal cells was observed and it is suggested that EMD has no teratogenic effect at studied concentrations.

Background: Maternal diabetes can induce a number of developmental abnormalities including deformities of the face and palate and these teratogenic effects decrease by application of antioxidant drugs. In this study, the prophylactic effect of quercetin on fetal teratogenesis incidence from diabetes was evaluated.Materials and Methods: In this experimental study, 24 female Wistar rats were used into four groups. After intravenous injection of streptozotocin (50 mg/kg) and confirm of diabetes in 2 groups of rats, all rats were mated. One group of diabetic and non-diabetic rats received quercetin (75 mg/kg/ orally) in 0,7,14 and 20 days of gestation while two control groups received normal saline. Fetuses were collected at 20th day of gestation and after determination of weight and length were stained by Alizarin red - Alcian blue method and skeletal abnormalities was evaluated by stereomicroscope.Results: Cleft palate, wavy rib and rib adhesion incidence were 38.09%, 4.86% and 14.28% range in control diabetic group but their incidence were respectively decreased 16.12%, 0% and 0% by quercetin. Also, quercetin decreased skeletal anomalies incidence including sternum, and ribs.Conclusion: Quercetin as one antioxidant can decrease Teratogenicity induced by diabetes mellitus.