Prevention of fumonisin-induced maternal and developmental toxicity in rats by certain plant extracts

In earlier work we have reported that garlic and cabbage extracts can protect laboratory animals from the toxic effects of different mycotoxins. Previous research demonstrated that fumonisin (FB) induced developmental effects in mice, rats and hamsters. The objectives of the present study were to utilize the pregnant rat as an in vivo model to compare the potential of garlic and cabbage seed extracts to prevent the developmental toxicity of FB and the effects of these extracts on sphingolipid metabolism in dam and foetus livers. Six treatment groups included a control group, a group fed on an FB-containing diet (150 mg kg(-1) feed) and groups treated orally with garlic or cabbage extracts (5 mg kg(-1) body wt.) with or without FB during gestation days 6-15. Evaluations of toxicity were performed on day 20. These include: maternal (mortality, body weight, feed intake and litter weight), developmental (embryonic resorption, foetal body weight, foetal soft-tissue anomalies and foetal skeletal examinations) and maternal and foetal sphingolipid metabolism. Fumonisin alone resulted in significant decreases in feed intake, body weight gain, litter weight, number of live foetuses and foetal body weight, whereas it increased significantly the number of resorbed foetuses and the number of skeletal malformations (30.4% for skull and 26.08% for sternebrae) and also increased the sphinganine/sphingosine (Sa/So) ratio in dam but not fetus livers. Garlic alone or plus FB was comparable to the control regarding all the tested parameters. On the other hand, cabbage seed extract alone or plus FB resulted in 10% maternal mortality and a decrease in maternal body weight and litter weight. It resulted in 4.65% skull malformations in foetuses but it was comparable to the control with regard to the other tested parameters. It could be concluded that both garlic and cabbage seed extracts have protective effects in pregnant rats. Moreover, garlic extract was found to have a greater protective effect than cabbage seed extract.     

Teratogenicity Study of Ethylene Glycol in Rats

ABSTRACT

Ethylene glycol was administered in the diet to pregnant Fischer 344 rats on days 6 through 15 of gestation. Target dosage levels were 1.0, 0.2, 0.04, and 0.00 g/kg/day. There was no maternal toxicity, embryotoxicity, or increased incidence of malformations in fetuses from dosed dams. Positive control dams received 500 mg/kg of hydroxyurea on gestation day 11 and had fetuses with numerous soft tissue and skeletal malformations. Results are interpreted as preliminary indication of lack of teratogenicity of ethylene glycol.     

Developmental Toxicity Study of Glycolic Acid in Rats

ABSTRACT

The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl:CD®BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). in addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p=0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p=0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.     

Developmental toxicity assessment of the new fluoroquinolone antibacterial DW-116 in rabbits

DW-116 is a newly developed fluoroquinolone antibacterial with a broad spectrum against both Gram-positive and Gram-negative bacteria. We have reported recently that DW-116 is embryotoxic and teratogenic in rats. The present study was conducted to investigate the teratogenicity of DW-116, together with maternal toxicity and developmental toxicity using New Zealand White rabbits. The test chemical was administered by gavage to pregnant rabbits from gestational day (GD) 6 through to GD 18 at dose levels of 0, 5, 19.5 and 76.1 mg kg(-1) day(-1). All does were subjected to caesarean section on day 28 of gestation and their foetuses were examined for external, visceral and skeletal abnormalities. In the 76.1 mg kg(-1) group, a minimal maternal toxicity, as evidenced by decreased body weight gain during treatment period, was observed in pregnant rabbits. Significant embryo-foetal toxicity, including increased number of foetal deaths and delayed foetal ossification, was seen. However, no treatment-related morphological changes were detected in foetal external, visceral and skeletal examinations. There were no adverse effects on either pregnant dams or embryo-foetal development at 19.5 and 5 mg kg(-1). It was concluded that administration of DW-116 during the major organogenetic period in rabbits produced decreased maternal body weight gain, increased number of foetal deaths and foetal developmental delay but no evidence of teratogenicity. The no-observed-adverse-effect levels (NOAELs) of DW-116 are considered to be 19.5 mg kg(-1) day(-1) for does and embryo-foetuses, respectively.     

Evaluation of Bauhinia monandra aqueous and ethanol extracts in pregnant rats

Bauhinia monandra Kurz. (Fabaceae: Caesalpinioideae) is a plant widely employed in Brazilian folk medicine for hypoglycemia. However, little is known about the effect of maternal exposure to this plant on fetal development. The aqueous and ethanol extracts obtained from B. monandra dried leaves were administered to pregnant Wistar rats throughout gestation (day 1 to day 20) at 1,400 or 7,000?mg/kg/day (n = 6/group). Maternal toxicity was not observed in the dams of both groups, and was evaluated by observing body weight, water and food intake during treatment, by measuring serum biochemical levels of creatinine, urea, AST and ALT, and by studying the histopathology of liver, kidney, pancreas, spleen and uterus at the end of treatment (gestation day 20). Both extracts and doses did not impair reproductive performance or delay fetal development, measured by observing implantations and reabsorptions in the uterus, by counting the number of corpora lutea in ovaries, by recording the litter weight and number of live and dead fetuses and by analyzing possible skeleton and viscera malformations in the fetuses. Also, the aqueous extract promoted decreased post-implantation loss when compared to the control group. The aqueous and ethanol extracts from B. monandra dried leaves (1,400 or 7,000?mg/kg/day) did not cause maternal or fetal toxicities and the aqueous extract promoted increased implantation and decreased post-implantation loss in the pregnant rats.     

Developmental Toxicity Study with N-Methyldiethanolamine by Repeated Cutaneous Application to CD Rats

Abstract

Timed pregnant CD rats were dosed cutaneously with aqueous N-methyldiethanolamine (MDEA) daily from gestational day (gd) 6 to 15, inclusive. Dosages employed were 0, 250, 500, and 1000 mg/kg/day and were selected on the basis of maternal toxicity responses determined from a range-finding study. Observations for maternal toxicity included body weight, food consumption, and clinical signs. Prior to scheduled necropsy on gd 21, blood was obtained for hematological study. At necropsy, liver and kidney, which are putative target organs of ethanolamine toxicity, were weighed. Fetuses were evaluated for body weight, and for external, visceral, and skeletal anomalies. Severe skin irritation characterized by necrosis, ecchymoses, exfoliation, crusting, excoriation, erythema, and edema was noted in dams receiving 1000 mg/kg/day during the dosing period. Exfoliation, crusting, necrosis, and erythema persisted subsequent to the dosing period, but by sacrifice on gd 21, substantial repair of the dosing site had occurred. In dams receiving 500 mg/kg/day less severe skin irritation was noted, but no local irritation was seen at the dosage of 250 mg/kg/day. There were no effects on maternal body weight; gestational weight gain; food consumption; or liver, kidney, or gravid uterine weights at any of the MDEA-dosed groups. Dams from the 1000 mg/kg/day group had decreases in erythrocyte count, hemoglobin, and hematocrit. There were no effects on any gestational parameters, and no increases in the total number of malformations or variations (external, visceral, or skeletal) by category or individually. In conclusion, rat dams showed dose-dependent skin irritation following repeated cutaneous application of MDEA during pregnancy. In addition, maternal toxicity was also present as anemia in dams receiving 1000 mg/kg/day. Despite maternal toxicity, there was no evidence of developmental effects. The no-observed-adverse effect level was 250 mg/kg/day for maternal toxicity, and at or above 1000 mg/kg/day for embryofetal toxicity and teratogenicity.     

Teratogenicity study of ethylene glycol in rats

Ethylene glycol was administered in the diet to pregnant Fischer 344 rats on days 6 through 15 of gestation. Target dosage levels were 1.0, 0.2, 0.04, and 0.00 g/kg/day. There was no maternal toxicity, embryotoxicity, or increased incidence of malformations in fetuses from doses dams. Positive control dams received 500 mg/kg of hydroxyurea on gestation day 11 and had fetuses with numerous soft tissue and skeletal malformations. Results are interpreted as preliminary indication of lack of teratogenicity of ethylene glycol.     

Assessment of the no-observed-effect level (NOEL) of quinalphos in pregnant rats.

Technical quinalphos (0.5, 1.5, 2, 3 or 4.5 mg/kg body weight) was administered orally to pregnant rats from day 6-15 of gestation. At 3 and 4.5 mg/kg/day, quinalphos produced significant changes in hepatic ALT, ALP and serum ALT, AST, ALP and LDH activity along with hepatocellular changes in dams. The AchE activity in brain and red blood cells was also significantly inhibited at these two doses. At 0.5, 1.5 and 2 mg/kg/day, however, quinalphos did not produce any such changes. Up to a dose of 2 mg/kg/day there was no foetotoxic or teratogenic effect, as evidenced by number of implantation sites, percent resorption, foetal weight, morphological, visceral and skeletal evaluations. Hence, 2 mg/kg body weight of quinalphos could be considered as the no-observed-effect level (NOEL) on foetal and maternal toxicity in rats.     

Evaluation of anti-inflammatory effect of Withania somnifera root on collagen-induced arthritis in rats

Context: Withania somnifera (Linn.) Dunal (Solanaceae) has long been used as an herb in Ayurvedic and indigenous medicine and has received intense attention in recent years for its chemopreventive properties.

Objective: The present study focuses on the effect of W. somnifera root powder on the behavioral and radiological changes in collagen-induced arthritic rats.

Materials and methods: The rats were randomly divided into five groups: normal control, arthritic control, arthritic rats treated with W. somnifera root powder (at dose levels 600 and 800?mg?kg^?1) and arthritic rats treated with methotrexate (at dose level 0.3?mg?kg^?1). The treatment with W. somnifera (daily) and methotrexate (weekly) was initiated from the 20th day post collagen immunization and continued up until the 45th day. Arthritis was assessed macroscopically by measuring paw thickness, ankle size and body weight. Arthritic pain was assessed by toe-spread and total print length of the affected paw. Functional recovery due to the oral treatment of W. somnifera and methotrexate was assessed by sciatic functional index and rota rod activity.

Results: Administration of W. somnifera root powder (600?mg?kg^?1) to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery of motor activity and radiological score.

Discussion and conclusion: W. somnifera root has a protective effect against collagen-induced arthritis (CIA) in rats. The results suggest that W. somnifera root powder acts as an anti-inflammatory and antioxidant agent in decreasing the arthritic effects in collagen-induced arthritic rats.     

Effects of melamine on pregnant dams and embryo‐fetal development in rats

There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo‐fetal development in Sprague–Dawley rats following maternal exposure on gestational days (GD) 6–20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg^?1 per day (n = 8–10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg^?1 per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment‐related maternal or developmental effects were observed at doses ≤400 mg kg^?1 per day. These results show that 15‐day repeated oral dosing of melamine is embryo‐/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no‐observed‐adverse‐effect level of melamine for pregnant dams and embryo‐fetal development is considered to be 400 mg kg^?1 per day. Copyright © 2011 John Wiley & Sons, Ltd.     

Embryo lethality and teratogenicity of a new fluoroquinolone antibacterial DW-116 in rats

DW-116, 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-l-piperazinyl)-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride, is a newly developed fluoroquinolone antibacterial. The potential of DW-116 to induce developmental toxicity was investigated in Sprague-Dawley rats. DW-116 was administered by gavage to pregnant rats from days 6 to 16 of gestation at dose levels of 0, 31.3, 125, and 500 mg/kg per day. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. At 500 mg/kg, toxic effects including clinical signs of toxicity, suppressed body weight and decreased food intake were found in dams. An increase in the resorption rate, a decrease in the litter size, a reduction in the fetal weight, and a decrease in the placental weight were also seen. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 17.9, 74.2 and 8.3%, respectively. Characteristic malformations included oedema, cleft palate, dilated cerebral ventricle, hypoplasia of lung and ventricular septum defect. A dramatic increase in the incidence of skeletal variations (55.6%) and retardations (94.4%) and a decrease in the number of ossification centres of sternebra, metacarpals, metatarsals and sacrocaudal vertebra were also observed. At 125 mg/kg, a reduction in the placental weight and an increase in the incidence of skeletal variations were found. There were no signs of maternal toxicity or embryotoxicity at 31.3 mg/kg. These results indicate that the fluoroquinolone antibacterial DW-116 is embryotoxic and teratogenic at minimally maternally toxic dose and is minimally embryotoxic at nonmaternally toxic dose in rats. Received: 4 November 1999 / Accepted: 23 December 1999     

Developmental toxicity study of glycolic acid in rats.

The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl: CD BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p = 0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p = 0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.     

Developmental toxicity evaluation of nerve growth factor for injection in Wistar rats

Nerve growth factor (NGF) for injection is now used as an agent to cure peripheral nerve injury. To assess its potential embryo-lethal and teratogenic toxicity, five groups of pregnant Wistar rats received 0, 40, 200 and 1000U/kg NGF by muscle injection from gestational days (GD) 6 to 17. Maternal body weight was monitored at regular intervals throughout gestation. We selected 7mg/kg body weight cyclophosphamide (CPA) given to positive control group testing the Wistar rats of this study whether sensitive to teratogens or not. The dams were euthanized on GD 20, the day just before expected parturition. All fetuses were removed by cesarean section and examined for external, visceral and skeletal malformations under a dissecting microscope. There were no treatment-related maternal deaths. Our statistical findings were a reduction in maternal body weight and the occurrence of fetal body length shorten in 1000U/(kgday) dose group, which suggesting mild embryotoxicity of NGF. There were no major changes observed in other doses groups such as viable fetuses rate, resorption and dead fetuses rate, external, skeletal, visceral abnormality, fetal weight and length, tail length, indicating no evident maternal toxicity, embryotoxicity and teratogenicity resulted from NGF. Thus, it seems a favorable preclinical safety evaluation profile for NGF.     

Critical period and minimum single oral dose of ochratoxin A for inducing developmental toxicity in pregnant Wistar rats

Ochratoxin A (OTA), a potent in vivo teratogen, has been tested in various laboratory animal species. Present investigation was conducted to determine critical dose and critical time for the developmental toxicity of OTA in pregnant Wistar rats after single oral dose administration. OTA at different graded dose levels (2–4 mg/kg body weight) and at different gestation days (6–15), caused variable developmental defects in developing fetuses. OTA at 2.75 mg/kg body weight, dissolved in 0.1 M sodium bicarbonate (vehicle) and administered by oral intubation as a single dose on one of the gestational days 6–15, caused significant maternal toxicity in the dams and various gross, visceral and skeletal anomalies in the fetuses. The major gross malformations were external hydrocephaly, incomplete closure of skull and omphalocele. Internal hydrocephaly, microphthalmia, enlarged renal pelvis and renal hypoplasia were the main internal soft tissue anomalies. Major skeletal defects were developmental defects in skull bones, sternebrae, vertebrae and ribs. The gestational days 6 and 7 were found to be the most critical for the induction of teratogenicity in rats. Single oral dose of 2.75 mg/kg body weight OTA was found to be the minimum effective teratogenic dose in pregnant Wistar rats.     

Embryo-fetal development toxicity of prenatal exposure to penequine hydrochloride intramuscularly in rats.

The potential for penequine hydrochloride to induce maternal and embryo-fetal developmental toxicity was evaluated in Wistar rats. The drug was administered intramuscularly (i.m.) at dose levels of 0, 10, 30 or 50mg/kg/day to groups of pregnant rats from day 6 to 15 of gestation. All dams were observed for maternal body weights, food consumption and any abnormal change, and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. In the 50mg/kg/day group, maternal toxicity included an increase in the incidence of abnormal clinical signs, and decrease in the body weight and body weight gain. Developmental toxicity included an increase in the postimplantation loss, a decrease in the litter size, and a reduction in the gravid uterus weight. In addition, a statistically non-significant increase in the incidence of fetal external, visceral, and skeletal alterations including malformations and variations were seen in high-dose group. There were no treatment-related findings in maternal clinical and intrauterine observations, and fetal morphological examinations in mid-, low-dose and control groups. Thus, under the conditions of this study, the no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect-level (LOAEL) of penequine hydrochloride for both maternal and embryo-fetal toxicity in the Wistar rats were considered to be 30mg/kg/day and 50mg/kg/day, which are approximately 900 and 1500 above the therapeutic dosage, respectively.     

Reproductive and developmental toxicity of degradation products of refrigerants in experimental animals

The present paper summarizes the results of animal studies on the reproductive and developmental toxicity of the degradation products of refrigerants, including trifluoroacetic acid (TFA), carbon dioxide (CO₂), carbon monoxide (CO), carbonyl fluoride (CF), hydrogen fluoride (HF) and formic acid (FA). Excessive CO₂ in the atmosphere is testicular and reproductive toxic, embryolethal, developmentally neurotoxic and teratogenic in experimental animals. As for CO, maternal exposure causes prenatal and postnatal lethality and growth retardation, skeletal variations, cardiomegaly, blood biochemical, immunological and postnatal behavioral changes, and neurological impairment in offspring of several species. Very early studies of CO in rats and guinea pigs reported fetal malformations in exposed dams. The results of toxicological studies on sodium fluoride (NaF) were used to obtain insight into the toxicity of CF and HF, because CF is rapidly hydrolyzed in contact with water yielding CO₂ and HF, and NaF is similar in kinetics and dynamics to HF. Increased fetal skeletal variation, but not malformation, was noted after the maternal administration of NaF. Rat multiple-generation studies revealed that NaF caused retarded ossification and degenerative changes in the lung and kidney in offspring. There is a lack of information about the toxicity of TFA and FA.     

In Utero and Lactational Exposure to Fluoxetine in Wistar Rats: Pregnancy Outcomes and Sexual Development

This study evaluated the reproductive effects of fluoxetine exposure in utero and during lactation on pregnancy outcomes and the sexual development of offspring. Pregnant Wistar rats were treated daily with fluoxetine (0.4, 1.7 and 17 mg/kg/day) or distilled water by gavage from gestation day (GD) 7 to lactation day (LD) 21. A significant reduction in maternal body weight was observed during pregnancy and lactation in dams exposed to 17 mg/kg fluoxetine. Hormone analysis revealed an increase in progestagen and glucocorticoid metabolites on GD 15 and oestrogen and progestagen metabolites on LD 7 in dams treated with 17 mg/kg fluoxetine. Oestrogen metabolites also were increased on LD 7 in dams treated with 0.4 mg/kg fluoxetine. Besides that, an increase in the weight of the adrenal glands and a reduction in uterine weight in dams exposed to highest dose of fluoxetine were observed. Finally, pup birthweight and the viability and weaning indices also were reduced in animals exposed to 17 mg/kg fluoxetine. Overall, maternal hormonal changes were only observed at the highest dose tested, which also induced maternal and foetal toxicity. No significant changes were seen in dams or offspring exposed to therapeutic‐like doses.     

Withania somnifera shows a protective effect in monocrotaline-induced pulmonary hypertension

Abstract

Context: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored.

Objective: The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats.

Materials and methods: In preventive studies, W. somnifera root powder (50 and 100?mg/kg/d, p.o.) was administered from day 1 following single administration of MCT (60?mg/kg, s.c.) in Sprague–Dawley (SD) rats. After 35?d, right ventricular pressure (RVP) was measured in anesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100?mg/kg/d, p.o.) was administered from day 21 to 35 post-MCT administration.

Results: Preventive treatment with 50 and 100?mg/kg W. somnifera significantly reduced the RVP (32.18?±?1.273?mm?Hg and 29.98?±?1.119?mm?Hg, respectively, versus 42.96?±?1.789?mm?Hg of MCT) and all markers of RVH in MCT-challenged rats. There was an improvement in inflammation, oxidative stress and endothelial dysfunction, and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100?mg/kg) also reduced RVP and RVH.

Discussion: This study demonstrated that W. somnifera significantly protected against MCT-induced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.     

Developmental toxicity assessment of medicinal mushroom Antrodia cinnamomea T.T. Chang et W.N. Chou (higher Basidiomycetes) submerged culture mycelium in rats

Antrodia cinnamomea is a Taiwanese medicinal mushroom with high antioxidant and polysaccharide content. The objective of this study is to investigate developmental toxicity of A. cinnamomea in pregnant Sprague-Dawley rats. Animals were daily gavaged with A. cinnamomea mycelium at dosage levels of 0 (reverse osmosis water), 50, 150, and 500 mg/kg from gestation day (GD) 6 to 15. All dams were sacrificed on GD 20 and were subjected to cesarean section. Fetuses were examined for external, visceral, and skeletal abnormalities. All copulated females survived until the end of the study. No significant differences were recorded in body weight change, food consumption, and maternal gestational parameters. Only two fetal malformations were noted in 970 fetuses from the treatment groups. Some variations, such as enlarged fontanel, split sternebrae, absent sacral, absent caudal vertebral centra, absent thoracic centra, absent 13th-14th ribs, and fused ribs, were found during the skeletal examination, but no treatment-induced abnormalities occurred. No dose dependency was observed in any of the developmental variations. Overall observation of foetal malformations from rats given A. cinnamomea mycelium during pregnancy demonstrates that this material is not teratogenic at doses up to 500 mg/kg. It is concluded that A. cinnamomea BCRC 35398 mycelium has no teratogenic effects in female rats and is safe to be used as a functional food ingredient.     

Citrinin and endosulfan induced teratogenic effects in Wistar rats

Dietary exposures to food pollutants such as mycotoxin(s) or pesticide(s) are most significant due to their adverse effects on the production and reproduction in animals and the human population. The present investigation was conducted to evaluate the teratogenic potential of citrinin (CIT) and endosulfan either alone or in combination in pregnant rats during gestational days 6-20. Endosulfan (1 mg kg(-1) body weight, by oral intubation) and CIT (10 mg kg(-1) feed, through diet) when administered either alone or in combination in pregnant rats caused significant teratogenic effects in the developing fetuses. There was no maternal mortality, however, reduced maternal weight gain and number of live fetuses and increased fetal resorptions were recorded in all the treated groups. The fetal body weights and crown to rump lengths were significantly decreased and the per cent gross, visceral and skeletal anomalies were significantly increased in the fetuses of dams of all the treated groups. The internal hydrocephalus, cerebellar hypoplasia, microphthalmia, contracted and notched kidneys, multilobulated liver, dilated renal pelvis, incomplete ossification of skull bones, rib anomalies and sacral and caudal vertebrae agenesis were the important fetal malformations. The occurrence of fetal gross, skeletal and visceral malformations was more severe in the combination group, suggesting an additive interaction of CIT and endosulfan in inducing developmental toxicity in Wistar rats.