Commelina benghalensis (Wandering Jew) Linn exhibits abortifacient potentials and hepatotoxicity in pregnant Wistar rats via elevating indicators of oxidative stress and activating proinflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Commelina benghalensis Linn is a perennial plant with upright stems reaching a height of 1 m. Its stem is commonly used to induce abortion in traditional medicine. However, there are insignificant scientific data to evaluate such a claim. AIM OF THE STUDY: The study was conducted to determine the abortifacient and toxicological potential of ethanol extract of Commelina benghalensis Linn stem (EECBS) via selected proinflammatory and oxidative stress biomarkers in pregnant Wistar rats. MATERIALS AND METHODS: To determine the phytochemicals responsible for EECBS's toxicity and abortifacient effects, high-performance liquid chromatography-photodiode array detection (HPLC-PDA) and gas chromatography-mass spectrometry (GC-MS) was used. The abortion rate was determined by monitoring the markers of reproductive system failure in the experimental model. To assess rat hepatotoxicity, biochemical markers and immunohistopathological parameters were used. RESULTS: Results demonstrated the presence of isomeric benzene-mesitylene compounds in EECBS. Also, EECBS significantly altered the markers of liver function and oxidative damage while eliciting a significantly reduced (P < 0.05) number of live fetuses, number of corpora lutea, progesterone, estradiol, and luteinizing hormone, whereas the number of dead fetuses percentage vaginal opening, and post-implantation loss increased significantly (P < 0.05). Estrogenicity studies indicated a significant (P < 0.05) increase in uterine weight, uterine glucose, and ALP dose-dependently. Moreover, EECBS also caused a vaginal hemorrhage preceding the parturition. Also, EECBS treatment significantly increased levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and significantly elevated the expression of COX-2 protein in the liver. CONCLUSION: The current investigation established Commelina benghalensis Linn stem's abortifacient activity. Continuous use, on the other hand, may cause liver damage in pregnant rats by disrupting antioxidant defense mechanisms, promoting the production of pro-inflammatory cytokines, and increasing COX-2 expression. Hence, caution should be excised while consuming this plant's stem for medication purposes, especially during the gestational period.

Spontaneous abortion in cattle after consumption of Hesperocyparis (Cupressus) macrocarpa (Hartw.) Bartel and Cupressus arizonica (Greene) needles in Uruguay.

An outbreak of cattle abortion associated with the consumption of Hesperocyparis (Cupressus) macrocarpa and Cupressus arizonica needles has been reported in Uruguay. Twenty-five of 125 pregnant heifers in late-term pregnancy aborted after being introduced into a paddock containing numerous H. macrocarpa, C. arizonica and Casuarina cunninghamiana trees. There were no significant macroscopic or histological findings in the two fetuses analyzed. Abortifacient labdane acids were detected in the needles of H. macrocarpa (1.68%, D.W.) and C. arizonica (0.36%, D.W.) but none were found in C. cunninghamiana.

Adverse effects of Croton urucurana B. exposure during rat pregnancy.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton urucurana presents several beneficial pharmacological properties. In Brazil, women who intend to interrupt the pregnancy indiscriminately use extracts of this plant as an abortifacient agent. AIM OF STUDY: To evaluated the effect of aqueous extract of Croton urucurana latex on the maternal-fetal repercussions in rats. METHODS: Pregnant rats were randomly distributed into four experimental groups: Control=treated with water (vehicle); Treated 200=treated with a dose 200mg/kg; Treated 400=dose 400mg/kg and; and Treated 800=dose 800mg/kg. The rats were orally treated by gavage with Croton urucurana or vehicle (water) during whole pregnancy. At term of pregnancy, all rats were killed to obtain maternal blood and tissues samples and fetal weight and anomaly analyses. RESULTS: C. urucurana treatment (Treated 400 and Treated 800) showed elevated liver enzymatic activities, reduced fetal body weight and placental efficiency. The Treated 800 group presented increased maternal total protein and cholesterol levels, and heart relative weight. All treated groups presented reduced maternal body weight and food intake, and increased pre-implantation loss rate compared to those of Control group. In addition, the treatment contributed to increased skeletal and visceral anomalies with higher doses. CONCLUSION: Croton urucurana treatment caused maternal toxicity, which contributed for impairment embryo fetal development. These results showed that the indiscriminate use of plants during pregnancy should be avoided to prevent potential risk on maternal health as well as their offspring.

Abortifacient potential of methanolic extract of Anthocephalus cadamba stem bark in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants possessing abortifacient activity have been used traditionally for a long time in folk medicine. Anthocephalus cadamba, is one such herb that has been known to possess abortifacient potential in ethnobotanical literature, but has not been validated scientifically. MATERIALS AND METHODS: The methanolic extract of Anthocephalus cadamba stem bark (MEAC) was prepared and tested for abortifacient, estrogenic and uterotrophic activity. Pregnant Swiss albino mice were randomized into 5 groups (1-5). Group 1 (negative control) received 0.2% w/v agar, group 2-4 (received extract at the dose of 500, 1000 and 1500mg/kg b.w.) and group 5 received mifepristone at a dose of 5.86mg/kg b.w. respectively, by oral route from 10(th) to 18(th) day post-coitum daily, and various parameters recorded. The uterotrophic bioassay was performed in bilaterally ovariectomized mice dosed from 9(th) to 15(th) day of ovariectomy and change in uterotrophic parameters was observed. RESULTS: Preliminary phytochemical screening revealed presence of glycosides, alkaloids, steroids, saponins, triterpenoids, flavonoids and tannins. No signs of clinical toxicity were observed at any time during the period of treatment. The extract significantly reduced (P<0.05) the number of live fetus, weight and survival ratio of the fetus, number of corpora lutea, progesterone, estradiol and luteinizing hormone whereas the number of dead fetus, number of mice that aborted, percentage vaginal opening and post-implantation loss increased significantly (P<0.05). The estrogenicity experiments showed increase in uterine weight (P<0.05), ballooning of uterus, uterine glucose (P<0.05) and ALP (P<0.001) in extract treated group dose dependently. In addition, the extract also induced vaginal bleeding preceding parturition. CONCLUSION: This study has substantiated the abortifacient potential of the methanolic extract of Anthocephalus cadamba stem bark. The activity was more marked in 1000 and 1500mg/kg b.w. of the extract and was comparable to that of mifepristone. The mechanism of abortion could possibly be through changes in the uterine mileu, altered hormone levels, luteolysis and partly, estrogenicity. This study thus justifies the ethnobotanical claim of MEAC as an abortifacient.

Abortifacient effect of metoclopramide in female albino rats.

BACKGROUND: Metoclopramide a dopamine receptor antagonist is commonly used to treat nausea and vomiting. Long term use can cause parkinsonism, galactorrhoea and gynaecomastia. As it is lipid soluble, it enters the brain, easily crosses the placental barrier and can affect the fetus. Hence, the present study is designed to assess the risk of metoclopramide in pregnant albino rats. OBJECTIVES: To study the abortifacient effect of metoclopramide in pregnant albino rats. METHODS: Eighteen pregnant rats were divided into three groups of six rats each. The abortifacient activities of metoclopramide were studied in the doses of 1 mg/kg and 3 mg/kg intramuscularly. The treatments were started on the 6th day of pregnancy and continued till the 15th day. Rats were laparotomised on 19th day of pregnancy for evaluation of abortifacient action. In both the horns of the uterus, number of implantation sites, resorption sites, dead and live fetuses were observed. RESULTS: The mean percentage of aborted fetus was 17.22 +/= 21.13 33.88 +/= 37.73 after 1mg/kg and 85.21 +/=18.93 after 3mg/kg of metoclopramide. The abortifacient effect of higher dose was significantly larger compared to both control group and low dose group, but there was no significant difference between the mean percentage of abortion in control group and the low dose group of metoclopramide. CONCLUSION: Metoclopramide at 3mg/kg intra muscular has abortifacient effects in female albino rats.

Exposure of mares to processionary caterpillars (Ochrogaster lunifer) in early pregnancy: an additional dimension to equine amnionitis and fetal loss.

REASONS FOR PERFORMING STUDY: Equine amnionitis and fetal loss (EAFL) is an unusual form of abortion in mid- to late-gestation mares, first identified in Australia in 2004. It has been shown that both whole processionary caterpillars (Ochrogaster lunifer) and their shed exoskeletons can induce abortion in mares during midgestation. These abortions exhibited gross pathology and bacteriology results consistent with field cases of EAFL. OBJECTIVES: To determine whether exposure of mares to the shed exoskeletons of processionary caterpillars can induce abortion in the preplacentation (<35 days' gestation) and early placentation (45-60 days) stages of pregnancy. STUDY DESIGN: In vivo experimental study. METHODS: Mares less than 35 days' gestation and between 45 and 60 days' gestation were exposed to a slurry of shed processionary caterpillar exoskeletons by nasogastric intubation. Mares were monitored by clinical examination daily. Transrectal ultrasonography was performed daily (control and treated preplacentation mares, treated early placentation mares) or every second day (control early placentation mares). Uterine swabs were collected from mares that aborted. All live foals underwent a clinical examination. Placentas were examined, with sampling for bacteriology and histopathology if appropriate. RESULTS: Abortions occurred in treated mares in both experiments without signs of impending abortion. One mare aborted in the embryonic stage experiment and 2 in the early placentation experiment. Embryonic and fetal death was detected on transrectal ultrasonography prior to abortion. In the early placentation experiment, one foal was born 5 weeks preterm and was very small, with laxity of the tendons in all limbs. Enteric or environmental bacteria, consistent with EAFL, were isolated from the mares that aborted. Focal mucoid placentitis lesions were present on the placentas of 2 treated mares, one from each experiment. CONCLUSIONS AND POTENTIAL RELEVANCE: Processionary caterpillar exposure may be associated with EAFL-related embryonic and early fetal loss in mares. Processionary caterpillars may also play a role in the occurrence of focal mucoid placentitis.

Abortifacient activity of Plumeria rubra (Linn) pod extract in female albino rats.

To evaluate the potential abortifacient activity of the aqueous, alcohol, ethyl acetate and chloroform extracts of P. rubra pod in female albino rats 50, 100 and 200 mg/kg body weight doses of each extract were administered from day 11 to 15 of pregnancy and animals were allowed to go full-term. The phytochemical screening revealed the presence of alkaloids, flavonoids, simple phenolics, steroids, tannins and saponins. Clinical toxicity symptoms such as respiratory distress, salivation, weight loss, dull eyes, diarrhea, and change in the appearance of fur as well as mortality were not observed in the animals at any period of the experiment. All the four extracts of P. rubra pods exhibited abortifacient activity (8-100%). The extracts significantly reduced the number of live fetuses, whereas the resorption index and post implantation losses increased significantly. The % of abortion was found to be highest (100%) with 200 mg/kg dose of alcoholic extract of P. rubra pods.

A comparison of the metabolism of the abortifacient compounds from Ponderosa pine needles in conditioned versus naive cattle.

Isocupressic acid (ICA) is the abortifacient compound in ponderosa pine (Pinus ponderosa L.) needles, which can cause late-term abortions in cattle (Bos taurus). However, cattle rapidly metabolize ICA to agathic acid (AGA) and subsequent metabolites. When pine needles are dosed orally to cattle, no ICA is detected in their serum, whereas AGA is readily detected. Recent research has demonstrated that AGA is also an abortifacient compound in cattle. The observation has been made that when cattle are dosed with labdane acids for an extended time, the concentration of AGA in serum increases for 1 to 2 d but then decreases to baseline after 5 to 6 d even though they are still being dosed twice daily. Therefore, in this study we investigated whether cattle conditioned to pine needles metabolize ICA, and its metabolites, faster than naïve cattle. Agathic acid was readily detected in the serum of naïve cattle fed ponderosa pine needles, whereas very little AGA was detected in the serum of cattle conditioned to pine needles. We also compared the metabolism of ICA in vitro using rumen cultures from pine-needle-conditioned and naïve cattle. In the rumen cultures from conditioned cattle, AGA concentrations were dramatically less than rumen cultures from naïve cattle. Thus, an adaptation occurs to cattle conditioned to pine needles such that the metabolism AGA by the rumen microflora is altered.

Equine amnionitis and fetal loss: mare abortion following experimental exposure to Processionary caterpillars (Ochrogaster lunifer).

REASONS FOR PERFORMING STUDY: In Australia, there have been recent reports of unusual abortions in mid- to late-gestation mares. These were clinically distinct from other recognised causes of pregnancy loss and the term 'equine amnionitis and fetal loss' (EAFL) was adopted to describe this syndrome. Initial investigations concluded that possible causal factors included the presence on affected stud farms of Processionary caterpillars (Ochrogaster lunifer). OBJECTIVES: To determine if exposure of pregnant mares to Processionary caterpillars or their shed exoskeletons can induce EAFL. METHODS: Processionary caterpillars and their shed exoskeletons were collected and stored frozen. Mid-gestation mares were dosed with a slurry of caterpillars or shed exoskeleton by nasogastric intubation. Their clinical responses and times to abortion were recorded. All aborted fetuses were autopsied and samples taken for bacteriological and virological culture and histopathology. RESULTS: Intubating mares in mid-pregnancy with preparations of either whole Processionary caterpillars or shed caterpillar exoskeletons induced abortion with few impending clinical signs. The gross pathological and bacteriological findings of the aborted fetuses were similar to those observed in field cases of EAFL. POTENTIAL RELEVANCE: Possible exposure to Processionary caterpillars should be considered when examining cases of fetal loss in the mare. The present results provide a starting point to further explore the aetiology and pathogenesis of EAFL.

Methotrexate and misoprostol teratogenicity: further expansion of the clinical manifestations.

We describe a boy who was exposed to misoprostol and methotrexate in the first trimester of gestation as a result of a failed medical abortion. He presented with severe growth retardation, skull defects, proptotic eyes, cleft palate, and severe micrognathia. There were bilateral defects of the upper and lower extremities, missing and hypoplastic ribs, and undescended testicles. He had clinical features of pulmonary hypoplasia with severe persistent pulmonary hypertension and remained ventilator-dependent until he expired. An autopsy revealed brain anomalies consistent with arrhinencephaly. Methotrexate is frequently used in conjunction with misoprostol to induce medical abortion, an off-label use as abortifacient. Both of these medications are well-established teratogens and have an X classification during pregnancy. Data from eight patients who were exposed to both medications in the first trimester indicate a significant teratogenic risk to the developing fetus. Reported anomalies include growth retardation, absence or hypoplasia of the frontal bones, craniosynostosis, large fontanelle, ocular hypertelorism, short palpebral fissures, wide nasal bridge, malformed and low-set ears, and micrognathia. Skeletal anomalies are frequent consisting of syndactyly, mesomelic shortening of the forearms, missing ribs, dislocated hips, and talipes equinovarus. The findings in our case are consistent with the pattern of abnormalities that have been reported in the literature. In addition, our patient had severe pulmonary hypoplasia and arrhinencephaly, anomalies that have not been described previously. This case adds to the documentation of the teratogenic effects of methotrexate and misoprostol on the developing fetus.

Effect of aqueous extract of Phyllantus amarus leaves on implantation and pregnancy in rats.

Phyllanthus amarus is a medicinal plant used widely in the treatment of many diseases. It has a long tradition of use in the Hindu Ayurvedic system of medicine and it has long been used as a medicinal agent in cultures around the world. Traditionally, in the Yoruba speaking part of western Nigeria it is used in treating sterility and difficult childbirth. This experiment was therefore designed to scientifically test the effect of aqueous extract of Phyllanthus amarus (AEPA) leaves on implantation and pregnancy. Animals were divided into two groups of 18 rats each after pregnancy has been established. Group I received 0.2mg/100g body weight of AEPA from day 1 of pregnancy. Group II received equal volume of distilled water serving as the control. Six rats from each group were sacrificed on days 6, 8 and 19 respectively. Implantation and pregnancy were assessed. AEPA reduced the time frame for implantation in the treated rats and caused abortion of pregnant rats. Although the aqueous extract of Phyllanthus amarus reduces the time frame for implantation, its abortificent effect does not support the traditional claim that it can treat sterility.

The guinea pig as an animal model for developmental and reproductive toxicology studies.

BACKGROUND: Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. METHODS: This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. RESULTS: A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. CONCLUSION: In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies.

Effects of Radix scutellariae and Rhizoma atractylodis on LPS-induced abortion and the uterine IL-10 contents in mice.

In the present study, lipopolysaccharide (LPS) was injected i.v. via the tail vein (0.1 microg per mouse) to induce abortion (embryo resorption) in Kunming mice. The interleukin 10 (IL-10) contents in the uterus were assayed by ELISA. The results revealed that the IL-10 level was significantly decreased in the LPS-induced abortion group of mice compared to the controls. Use of Pentoxifylline (PXF), or a combination of Radix scutellariae and Rhizoma atractylodis reversed the LPS effects: bringing down the fetal resorption rate, and increasing the IL-10 level significantly. The study indicates that the anti-abortive effects of PXF and the combination of Radix scutellariae and Rhizoma atractylodis are closely related to up-regulation of the Th2 cytokine IL-10 at the maternal fetal interface.

Effects of thalidomide on developmental, peri- and postnatal function in female New Zealand white rabbits and offspring.

The present study determined effects of thalidomide on three successive generations of New Zealand White rabbits after oral dosing to F0 maternal rabbits during the later third of gestation (post major organogenesis) and lactation. One hundred and twenty four time-mated F0 rabbits (31/dose) were gavaged with 0, 30, 150, or 500 mg/kg thalidomide from gestation day 18 (DG 18) to lactation day 28 (DP or day postpartum 28) for approximately 42 days. At 6 months, 12 F1 males and 12 F1 females were randomly paired within each dose group and mated. Reproductive evaluation and/or gross necropsy of the thoracic, abdominal, and pelvic viscera was performed on day 29 postpartum (DP 29) for F0 rabbits, on DP 49 for F1 pups not selected for continued evaluation, after completion of mating for F1 rabbits, and on DG 29 for F1 rabbits on continued evaluation of F2 litter. There was no thalidomide-related mortality in F0 and F1 rabbits. One F0 doe at 30 and 150 mg/kg and 2 at 500 mg/kg aborted. Maternal F0 rabbits had reductions in feed consumption but not body weight gain during the gestation and lactation periods for 150 and 500 mg/kg. The numbers of does with stillborn and all pups dying from DP 1-4 was increased at 150 and 500 mg/kg. Mean number of liveborn (litter size) and percentage of live pups were decreased at 500 mg/kg. A significantly increased number of pups died at 150 and 500 mg/kg, resulting in a reduced viability index and decreased litter size. There were some F1 male and female body weight reductions at 150 and 500 mg/kg postweaning with no change in feed consumption. F1 Caesarean-sectioning and litter observations were normal. Fertility of F1 offspring was not affected by maternal doses of thalidomide, but the pregnancy index may have been reduced by the 500 mg/kg maternal thalidomide dose. There was an apparent dose-related increase in splayed limbs in F1 pups. Splaying has been reported in New Zealand White rabbits and may be a recessive trait. The splay could be caused by the nerve and muscle fiber degeneration and skeletal muscle atrophy observed in some pups. It could also be due to the decrease in litter size, resulting in fewer pups per litter for nursing, leading to rapid weight gain and a failure of the pups to support this weight. No F2 fetal gross external alterations were observed. In summary, pregnant rabbits orally dosed with up to 500 mg/kg thalidomide from gestation day 18 to lactation day 28 had increased abortion, changes in some natural delivery and litter parameters, and limb splay in some F1 pups. No gross external changes were observed in F1 and F2 pups.

Antifertility activity of Derris brevipes variety coriacea.

Traditional physicians in and around Kotagiri village near Ootacamund, use a mixture of powdered roots of Cassia occidentalis, Derris brevipes variety coriacea and Justicia simplex to control female fertility. A mixture of powdered roots of these three plants, powdered root of Derris brevipes variety coriacea and its ethanolic extract were screened for antifertility activity in proven fertile female rats at 200 and 600 mg/kg body weight, respectively and given orally on D(1-7) of pregnancy. Both doses of the root powder of Derris brevipes variety coriacea showed 50% anti-implantation activity and also a significant reduction in the number of litters born. The ethanolic extract exhibited 40% anti-implantation activity when given orally at 600 mg/kg body weight. The rats, which continued their pregnancy, did not deliver any litters after their full term. Hence, the combined antifertility (anti-implantation and abortifacient) activity of the ethanolic extract was 100%. The results suggest that the ethanolic extract possesses more abortifacient type effect than the anti-implantation activity. The ethanolic extract also exhibited weak estrogenic activity when given alone and tested in immature ovariectomised female albino rats. But, when given along with ethinyl estradiol, it exhibited slight antiestrogenic activity. Histological and biochemical estimations were carried out to confirm this.

Abortifacient properties of aqueous extract of Carica papaya (Linn) seeds on female Sprague-Dawley rats.

Experiments were conducted to investigate the abortifacient potential of aqueous extract of Carica papaya (Linn) seeds in female Sprague-Dawley rats. Oral doses of 100 and 800 mg/kg body weight were administered once a day on days 1-10 post-coitum. No significant differences in total body weight were found in foetuses exposed to these regimes. However, in the group treated with 100 mg/kg body weight, there was a significant increase (p < 0.05) in the implantation sites and foetal weight was significantly decreased (p < 0.05) compared to the controls. No dead or malformed foetuses were found. However, in the group treated with 800 mg/kg body weight, there was obvious vaginal bleeding but no treatment related increase in implantation sites compared with control. There was however, complete resorption of about 30% of the foetuses. The surviving foetuses were stunted when compared with the control but were without any external malformations. The results of the present investigations lead to the clear conclusion that low dose aqueous crude extract of Carica papaya (Linn) seeds does not adversely affect prenatal development. The altered toxicological profile indicates that the abortifacient property is a high dose side effect. The results indicate that Carica papaya toxicity can adversely affect the foetus.

The toxic effects of Coleus barbatus B. on the different periods of pregnancy in rats.

Extracts of Coleus barbatus B. have been used in folk medicine to interrupt pregnancy. In order to evaluate if this plant interferes with embryo implantation or with the normal development of the concepts, pregnant Wistar rats were treated with increasing doses (220, 440 and 880 mg/kg per day) of a hydroalcoholic extract of C. barbatus. The rats received the extract by gavage from days 0 to 5 of pregnancy (preimplantation period) or 6 to 15 (organogenic period). Control groups received distilled water during the same periods. The animals were killed at term for the evaluation of maternal and fetal parameters. The results showed that the treatment with 880 mg/kg per day of the extract of C. barbatus before embryo implantation caused delayed fetal development and an anti-implantation effect, which justifies the popular use of this extract with abortive purposes. After embryo implantation delayed development associated with maternal toxicity was observed in the fetuses of the group which received 880 mg/kg per day.

Abortifacient effects of lodgepole pine (Pinus contorta) and common juniper (Juniperus communis) on cattle.

Lodgepole pine (Pinus contorta) and common juniper (Juniperus communis) contain high levels of isocupressic acid that has been identified as the abortifacient component of ponderosa pine needles in cattle. Therefore, the abortifacient potential of P contorta and J communis needles was tested in feeding trials with pregnant cattle. Cows (2 groups of 2 each) were fed by gavage 4.5-5.5 kg/d ground dry needles from either P contorta or J communis starting on gestation day 250. Isocupressic acid (ICA) levels in P contorta needles and J communis plant material were 0.8 and 2.0% (dry weight) respectively. Cows fed P contorta received a daily dose of 62-78 mg ICA/kg body weight and aborted after 8 and 10 d. The 2 cows fed J communis received a daily dose of 190 and 245 mg ICA/kg body weight and aborted after 3 and 4 days respectively. All cows retained fetal membranes and had classical clinical signs of pine needle-induced abortion. Pinus ponderosa, P contorta, J communis, and Cupressus macrocarpa samples were also analyzed for the presence of myristate and laurate esters of 1,14-tetradecanediol and 1,12-dodecanediol. These lipid like compounds of P ponderosa have potent vasoconstrictive activity in a placentome perfusion assay and are proposed as possible abortifacients in cattle. Concentration of the vasoactive lipids were 0.028% (P ponderosa), 0.023% (P contorta), 0.001% (J communis), and none detected (C macrocarpa). It was concluded that these compounds are not required for the plant material to be abortifacient in cattle.

Abortive and teratogenic effect of Acanthospermum hispidum DC. and Cajanus cajan (L.) Millps. in pregnant rats.

Extracts of Acanthospermum hispidum and Cajanus cajan have been used by Brazilian people in an attempt to produce abortion. In order to evaluate the possible abortive and/or teratogenic effect of these plant extracts, female Wistar rats were treated with the aqueous extract (infusion, proportion C. cajan and A. hispidum 1:1.3). Doses of 0, 150, 300 and 600 mg/kg were daily administered by gavage during the organogenic period. The animals were sacrificed at term. There was no significant change in the mean weight of the fetuses, and no change in the percentage of post implantation loss in the treated groups. However, there was an increase in the number of external malformations, and this was related to dose. No internal malformations were observed in fetuses at term, but there was a significant incidence of fetuses with visceral anomalies. The tendency of the pregnancy to continue or terminate did not change with the treatment.

Effect of feeding ponderosa pine needle extracts and their residues to pregnant cattle.

Solvents including ethanol, methylene chloride, acetone, hexane, and hot and cold water were used in separate procedures to extract needles and bark from ponderosa pine (Pinus ponderosa L.) to determine which system was optimal for the extraction of abortifacient compound(s). The extracts and residues therefrom were fed by gavage to pregnant cows beginning at day 250 of gestation. After methylene chloride extraction, the pine needle residue fed by gavage failed to abort 4 cows. Subsequently, 4 cows fed the methylene chloride extractable material, adsorbed on ground hay, but free of methylene chloride, aborted (days 253-260 of gestation) and all 4 cows retained fetal membranes. Only 2 of 6 cows fed the pine needle residue after ethanol extraction aborted (days 260 and 261 of gestation) and both retained their fetal membranes, while the other 4 cows calved normally. Hot and cold water extracts did not cause abortion, whereas the extracted plant residue did. One cow fed the plant residue after acetone extraction calved normally as did 1 of 2 cows fed residue after hexane extraction. One cow fed hexane extract absorbed on ground hay also calved normally. These results demonstrate that abortifacient compound(s) present in pine needles are most efficiently extracted by methylene chloride.