Evaluation of developmental toxicity induced by anticholinesterase insecticide,diazinon in female rats

Developmental toxicities, including birth defects, are significant public health problems. This study was planned to assess the cholinergic and developmental potentials of diazinon that is widely used as an organophosphate insecticide. Pregnant female Sprague‐Dawley rats were given diazinon orally at doses of 0, 1.9, 3.8, and 7.6 mg/kg body weight (b.w.)/day on gestation days 6 to 15. Maternal brain acetylcholinesterase activities, measured on gestation day20, were significantly decreased at 3.8 and 7.6 mg/kg b.w./day, but fetal acetylcholinesterase activity was not altered. Maternal toxicities, as evidenced by cholinergic symptoms including diarrhea, tremors, weakness, salivation, and decreased activities, were observed at the 3.8 and 7.6 mg/kg b.w./day dose groups. Net gravid uterine weight was decreased at a dose of 7.6 mg/kg b.w./day. No maternal effects were apparent in the 1.9 mg/kg b.w./day dose group. Maternal toxicity at a dose of 3.8 mg/kg b.w./day did not induce fetotoxicity or teratogeneicity. However, 7.6 mg/kg b.w./day doses significantly resulted in fetal toxicity and malformations in addition to maternal toxicity in animals. In conclusion, teratogenic disorders only outlined by doses that produced marked maternal toxicity. Since the malformations were not morphologically related, they were considered to be secondary to maternal toxicity; hence, the malformations were not related to cholinesterase inhibition. Birth Defects Res (Part B) 92:534–542, 2011. © 2011 Wiley Periodicals, Inc.     

Maternal and developmental toxicity of ayahuasca in Wistar rats

INTRODUCTION: Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. METHODS: In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five‐fold TD and 10‐fold TD] during the gestational period (6–20 days). RESULTS: Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate‐ and high‐dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. CONCLUSIONS: From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose‐dependent. Birth Defects Res (Part B) 89:207–212, 2010. © 2010 Wiley‐Liss, Inc.     

顺铂诱导肾损伤过程中肾皮质脂质过氧化的变化

目的:探讨顺铂肾损伤过程中肾皮质脂质过氧化与肾小管结构改变的关系.方法:雌性Wistar大鼠随机分为生理盐水组、顺铂Ⅰ组、顺铂Ⅱ组、顺铂Ⅲ组,均为尾静脉注射给药,每天一次,连续五天.第六天取血测肌酐(Scr)、尿素氮(BUN)含量,取肾皮质测丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性,同时进行肾小管上皮细胞碱性磷酸酶组织化学染色和组织病理学观察.结果:顺铂组Scr、BUN明显升高,肾皮质MDA含量升高,SOD与GSH-Px活性降低,与对照组相比均有显著差异(P＜0.05),且肾皮质SOD活性、GSH-Px活性与Scr、BUN含量呈明显负相关(P＜0.05),肾皮质MDA含量与Scr、BUN含量呈明显正相关(P＜0.05).酶组化显示肾小管上皮细胞碱性磷酸酶大量丢失,病理切片结果显示肾皮质部分肾小管上皮细胞变性、坏死.结论:顺铂引起肾皮质组织的破坏与肾皮质脂质过氧化增强有关,且随剂量增加肾皮质损伤加重.     

Localization of glycogen in the placenta and fetal and maternal livers of cadmium-exposed diabetic pregnant rats

This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200–220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl₂ dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on d 13 of pregnancy by a single intraperitoneal injection of STZ in the STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on d 13 of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on d 15 and d 20 of pregnancy. Blood samples were taken for determination of the serum glucose and insulin levels. Fetal and maternal livers of sacrificed rats in all groups were harvested on d 15 and d 20 of pregnancy, whereas placentas were harvested only on d 20 of pregnancy for histochemical examination. Although both Cd and STZ caused hyperglycemia and decreased insulin secretion, Cd-alone treatment increased the glycogen content only in the placental labyrinth, whereas STZ-alone treatment increased the glycogen content only in the maternal part of the placenta. Increased glycogen localization was observed in both the placental labyrinth and the maternal part of placenta when Cd and STZ were given together. Fetal and meternal livers of control and other treatment groups were not different regarding the glycogen content on d 15 or d 20 of pregnancy. It was concluded that Cd exposure during pregnancy might produce a glycogen localization in the placenta of diabetic rats. However, the function and the mechanisms of increased glycogen contents in the placenta of Cd-exposed pregnant diabetic rats remain unclear and further studies are needed.     

Dose–Response Effects of Diphenylhydantoin on Pregnant Dams and Embryo‐Fetal Development in Rats

Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose–response relationship of DPH. This study investigated the dose–response effects of DPH on pregnant dams and embryo‐fetal development as well as the relationship between maternal and developmental toxicity. DPHwas orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day. At 300 mg/kg, maternal toxicity including increased clinical signs, suppressed body weight, decreased food intake, and increased weights of adrenal glands, liver, kidneys, and brain were observed in dams. Developmental toxicity, including a decrease in fetal and placental weights, increased incidence of morphological alterations, and a delay in fetal ossification delay also occurred. At 150 mg/kg, maternal toxicity manifested as an increased incidence of clinical signs, reduced body weight gain and food intake, and increased weights of adrenal glands and brain. Only minimal developmental toxicity, including decreased placental weight and an increased incidence of visceral and skeletal variations, was observed. No treatment‐related maternal or developmental effects were observed at 50 mg/kg. These results show that DPH is minimally embryotoxic at a minimal maternotoxic dose (150 mg/kg/day) but is embryotoxic and teratogenic at an overt maternotoxic dose (300 mg/kg/day). Under these experimental conditions, the no‐observed‐adverse‐effect level of DPH for pregnant dams and embryo‐fetal development is considered to be 50 mg/kg/day. These data indicate that DPH is not a selective developmental toxicant in the rat.     

Changes in alkaline phosphatase activity and phosphate uptake in P-limited phytoplankton,induced by light intensity and spectral quality

Alkaline phosphatase activity and P uptake were determined in P-limited Dunaliella tertiolecta, Thalassiosira pseudonana, Phaeodactylum tricornumtum, and Prymnesium parvum grown under different light intensities and colors. Both intracellular and extracellular enzyme activities varied with the intensity and quality of light in a species-specific manner. The spectral composition of the light also affected P uptake kinetics. No correlation was found between enzyme activity and V_max both within a species and for pooled data for all four species, indicating that the change in uptake kinetics and enzyme activity was not related to P limitation, but induced by the light conditions. Changes in the optimum N:P ratio induced by light were also not related to P uptake kinetics or enzyme activity. These data suggest that light conditions may in themselves have profound effects on species competition for limiting nutrients. Furthermore, since both alkaline phosphatase activity and P uptake were influenced by the prevailing light conditions we suggest that these parameters be used cautiously when determining the P nutritional status of phytoplankton in nature.Address for reprint requests     

Inhibiting matrix metalloproteinases with prinomastat produces abnormalities in fetal growth and development in rats

BACKGROUND: Matrix metalloproteinases (MMPs) play key roles in remodeling of the extracellular matrix during embryogenesis and fetal development. The objective of this study was to determine the effects of prinomastat, a potent selective MMP inhibitor, on fetal growth and development. METHODS: Prinomastat (25, 100, 250 mg/kg/day, p.o.) was administered to pregnant female Sprague-Dawley rats on gestational days (GD) 6-17. A Cesarian section was carried out on GD 20 and the fetuses were evaluated for viability and skeletal and soft tissue abnormalities. RESULTS: Prinomastat treatment at the 250 mg/kg/day dose produced a decrease in body weight and food consumption in the dams. A dose-dependent increase in post-implantation loss was observed in the 100 and 250 mg/kg/day-dose groups, resulting in only 22% of the dams having viable litters for evaluation at the 250 mg/kg/day dose. Fetal skeletal tissue variations and malformations were present in all prinomastat treated groups and their frequency increased with dose. Variations and malformation in fetal soft tissue were also increased at the 100 and 250 mg/kg/day doses. Prinomastat also interfered with fetal growth of rat embryo cultures in vitro. CONCLUSIONS: These data confirm that MMP inhibition has a profound effect on fetal growth and development in vivo and in vitro.     

Incorporation of3H-thymidine into DNA and the activity of alkaline phosphatase in zinc-deficient fetal rat brains

The incorporation of³H-thymidine into DNA in the brains of the 17-day and 20-day old rat fetuses was significantly reduced by maternal zinc restriction during pregnancy. The activity of the enzyme thymidine kinase (EC 2.7.1.21) was similarly reduced in the zine-deprived fetal brains on days 14 and 20 of gestation, but not on day 17. Fetal brain alkaline phosphatase (EC 3.1.3.1) was significantly depressed by maternal zinc deprivation on days 17 and 20 of pregnancy. The data suggest an association between thymidine kinase and the reduced incorporation of³H-thymidine into DNA in the brains of 20-day old fetuses but not in animals on day 17. Alkaline phosphatase was however depressed at this stage. The suggestion is made that because of the complexity of brain development, future biochemical studies in this area should concern specific structures in the brain at particular critical stages during neurogenesis.     

Effects of tert-butyl acetate on maternal toxicity and embryo-fetal development in Sprague-Dawley rats

This study investigated the potential adverse effects of tert-butyl acetate (TBAc) on maternal toxicity and embryo-fetal development after maternal exposure of pregnant rats from gestational days 6 through 19. TBAc was administered to pregnant rats by gavage at 0, 400, 800, and 1,600 mg/kg/day. All dams were subjected to a Caesarean section on day 20 of gestation, and their fetuses were examined for any morphological abnormalities. At 1,600 mg/kg, maternal toxicity manifested as increases in the incidence of clinical signs and death, lower body weight gain and food intake, increases in the weights of adrenal glands and liver, and a decrease in thymus weight. Developmental toxicity included a decrease in fetal weight, an increase in the incidence of skeletal variation, and a delay in fetal ossification. At 800 mg/kg, only a minimal developmental toxicity, including an increase in the incidence of skeletal variation and a delay in fetal ossification, were observed. In contrast, no adverse maternal or developmental effects were observed at 400 mg/kg. These results show that a 14-day repeated oral dose of TBAc is embryotoxic at a maternally toxic dose (i.e., 1,600 mg/kg/day) and is minimally embryotoxic at a nonmaternally toxic dose (i.e., 800 mg/kg/day) in rats. However, no evidence for the teratogenicity of TBAc was noted in rats. It is concluded that the developmental findings observed in the present study are secondary effects to maternal toxicity. Under these experimental conditions, the no-observed-adverse-effect level of TBAc is considered to be 800 mg/kg/day for dams and 400 mg/kg/day for embryo-fetal development.     

Success rate of primary human endothelial cell culture from umbilical cords is influenced by maternal and fetal factors and interval from delivery

Summary There is increasing interest in human umbilical cord vein as a source of endothelial cells. This paper shows that success in setting up cultures of human endothelial cells from umbilical cords depends not only on culture conditions, as so far proposed, but also on factors preceding the harvesting of the cells. In particular, the mother's smoking habit and the use of umbilical cord within 1 h of delivery have been shown to impair success of the culture. Age, parity, diabetes, and hypertension of the mother, type of delivery, and sex and weight of the newborn did not significantly influence the possibility of establishing successful endothelial cell culture. This work was supported by the Italian National Research Council, Grant 82.00151.04.     

Chlorpromazine and other psychoactive drug induced alterations of a membrane bound enzyme in rat brain

Psychoactive drugs like chlorpromazine (CPZ), imipramine, lithium and amphetamine in one way or another affect behaviour. The drug responses are presumably mediated by inducing a change in the activity of membrane bound enzymes. CPZ is very potent in inhibiting the alkaline phosphatase activity in rat brain. The combined effect of CPZ with other drugs shows that CPZ and imipramine together inhibit the enzyme activity significantly greater than the individual inhibition either by CPZ or by imipramine alone. Effective inhibition of the alkaline phosphatase activity with a single drug or combined drugs may lead to a change in neuronal permeability through glucocorticoids thereby affecting mood.     

Maternal and fetal iron accumulation in Zn-deficient and salicylate-treated rats

Nonhemoglobin Fe (non Hb−Fe) content in fetal serum and liver is much higher than in maternal serum and liver. After feeding a Zn-deficient diet to pregnant rats from d 0 to 21, non Hb−Fe content in maternal and fetal serum and liver was increased. After oral application of salicylic acid (300 mg/kg) from d 16 to 20 to normally fed and Zn-deficient dams, non Hb−Fe content in maternal and particularly in fetal serum and liver was drastically increased. In the kidney, Fe was accumulated to a small amount resulting from Zn deficiency and salicylate treatment. Fe accumulation in the liver occurred in all cell fractions, particularly in microsomes. Fe accumulation was confirmed and extended histochemically by Prussian blue staining. It is assumed that salicylate increases intestinal Fe resorption and fetal transfer of Fe. It is discussed that salicylate nephrotoxicity and its enhancement by Zn deficiency is not caused by an Fe-dependent mechanism. This work is supported by the German Research Foundation (Sfb 174)     

Effects of gestational exposure to 1.95‐GHz W‐CDMA signals for IMT‐2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats

The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95‐GHz wide‐band code division multiple access (W‐CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT‐2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7–17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole‐body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243–271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses. Bioelectromagnetics 30:205–212, 2009. © 2008 Wiley‐Liss, Inc.     

Micro-computed tomography and alizarin red evaluations of boric acid–induced fetal skeletal changes in Sprague-Dawley rats

BACKGROUND: Assessment of developmental toxicity has historically included assessment of fetal skeletal morphology after alizarin red staining. X-ray micro-computed tomography (micro-CT) produces high-resolution images of skeletal structures and was investigated as an alternative method. METHODS: Groups of 5 mated Crl:CD (SD) female rats each were administered vehicle or boric acid (40 to 500 mg/kg/day) from GD 6 through 11. On GD 21, all live fetuses were weighed, euthanized, and viscera removed. Each litter was placed into a custom-made polystyrene holder and scanned in the micro-CT imaging system. Raw projection data were acquired in approximately 15 sec (∼20 litters per hour) and reconstructed images at 100-micron cubic voxel dimension could be viewed as early as 20 min later. Fetuses were subsequently stained with alizarin red, and findings recorded separately for each method without knowledge of treatment group. RESULTS: Micro-CT evaluation of fetal rat skeletons detected essentially the same skeletal malformations, variations, and incomplete ossifications as seen by the staining method. The specific skeletal abnormalities that did not match exactly involved the smallest skeletal elements with minimal degrees of ossification (i.e., cervical ribs, hypoplastic 13^th ribs, supernumerary ribs, the 5^th sternebra, and numbers of caudal vertebrae), but the differences did not impact the overall conclusions. Additional measures such as femur length were easily measured by micro-CT. CONCLUSIONS: These results indicate that micro-CT imaging can effectively assess rat fetal skeletal structures, and for those laboratories with this resource, it may be used to significantly reduce time prior to skeletal evaluation and hazardous wastes associated with staining. Birth Defects Res (Part B) 33:214–219, 2009 © 2009 Wiley-Liss, Inc.     

Canalization and developmental instability of the fetal skull in a mouse model of maternal nutritional stress

Nutritional imbalance is one of the main sources of stress in both extant and extinct human populations. Restricted availability of nutrients is thought to disrupt the buffering mechanisms that contribute to developmental stability and canalization, resulting in increased levels of fluctuating asymmetry (FA) and phenotypic variance among individuals. However, the literature is contradictory in this regard. This study assesses the effect of prenatal nutritional stress on FA and among‐individual variance in cranial shape and size using a mouse model of maternal protein restriction. Two sets of landmark coordinates were digitized in three dimensions from skulls of control and protein restricted specimens at E17.5 and E18.5. We found that, by the end of gestation, maternal protein restriction resulted in a significant reduction of skull size. Fluctuating asymmetry in size and shape exceeded the amount of measurement error in all groups, but no significant differences in the magnitude of FA were found between treatments. Conversely, the pattern of shape asymmetry was affected by the environmental perturbation since the angles between the first eigenvectors extracted from the covariance matrix of shape asymmetric component of protein restricted and control groups were not significantly different from the expected for random vectors. In addition, among‐individual variance in cranial shape was significantly higher in the protein restricted than the control group at E18.5. Overall, the results obtained from a controlled experiment do not support the view of fluctuating asymmetry of cranial structures as a reliable index for inferring nutritional stress in human populations. Am J Phys Anthropol 154:544–553, 2014. © 2014 Wiley Periodicals, Inc.     

Effect in rats of simultaneous prenatal exposure to ochratoxin A and aflatoxin B1. I. Maternal toxicity and fetal malformations

Ochratoxin A (OA) and Aflatoxin B1 (AFB1), the food borne mycotoxins are produced by several fungal species of the genera Aspergillus and Penicillium. To determine the teratogenic effects, these mycotoxins were administered orally either individually or in combination to the pregnant Wistar rats on days 6-15 of gestation. OA and AFB1 were dissolved in corn oil and different doses of OA (0.125, 0.25, 0.50, and 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, and 1.00 mg/kg), and a combination of OA+AFB1 (0.125+0.125; 0.25+0.50; 0.50+0.25 mg/kg) were given by gastric intubation to rats. During dosing period, the body weight and body weight gains significantly decreased at a higher dosage, in both individual and combined treatments. In all the combination treatments, the percent implants resorbed, fetal body weights, and crown-rump lengths were comparable to those of controls and with the individual mycotoxin treatment. The number of dead fetuses was significantly increased in the high OA combination (OA+AFB1 0.50+0.25) group as compared with the other two combinations. OA and AFB1 alone and in combination caused various gross, skeletal, and visceral anomalies. The occurrence was considerably less pronounced in fetuses of AFB1 and combination groups as compared with those of OA group fetuses. The exencephaly, incomplete closure of skull, wavy and fused ribs, agenesis of the ischium bone, and enlarged renal pelvis, recorded in OA treatment and ear abnormality and incomplete ossification of skull bones observed in AFB1 when given individually, were not seen in combination groups. However, new manifestations, such as gastroschisis and syndactyly were observed and the incidence of cardiac defects was increased in fetuses due to the combined treatment. The results of the present study indicated that there is some interaction between these mycotoxins that resulted in reduced teratogenic activity of OA in the presence of AFB1. Apparently, new manifestations observed in combination treatment points to the potential threat of teratogenicity in terms of public health hazards.     

β-ME和BHA体外诱导人胎肝CD34+细胞向神经组织细胞分化研究

目的:建立巯基乙醇(β-mercaptoethanol,β-ME)和丁羟回醚(butylated hydroxyanisole,BHA)体外诱导人胎肝(fetal liver,FL)干细胞向神经细胞分化模型.方法:采用MACS试剂盒分离人胚胎肝CD34 细胞,以DMEM 10%胎牛血清培养液培养;第五代细胞待细胞融合达80%后,用DMEM 10%胎牛血清 1mmol/L β-ME 0.2 mmol/L BHA诱导24 h,PBS洗涤.然后在无血清培养基中培养5 h～5 d.用免疫细胞化学方法分析诱导前后的细胞表型特点.结果:经β-ME BHA诱导处理后,细胞表现神经元样细胞形态,表达神经组织细胞特异蛋白,如neustin、NeuN、NF-M、TuJ-1和NSE.统计显示81%细胞NeuN染色阳性,75%细胞TuJ-1染色阳性,47%染色NF-M阳性,90%染色NSE阳性.结论:β-ME和BHA能够诱导体外培养的人FL CD34 细胞分化为具有神经细胞特异性抗原和成分的神经样细胞;胚胎肝细胞具有向神经组织分化的潜能.     

Effects of maternal uninephrectomy on the development of fetal rat kidney: Numerical and volumetric changes of the glomerulus and formation of the anionic site in the glomerular basement membrane

Developmental processes of the fetal rat kidney from uninephrectomized mothers were studied. The uninephrectomy was performed on day 5 of gestation. Glomerular number and volume in the fetal kidneys on days 18, 20, and 22 of gestation were morphometrically determined. To investigate the anionic site formation in the glomerular basement membrane, distribution of cationized ferritin (CF) in the fetal glomerulus was examined electron microscopically after CF injection. Blood urea nitrogen (BUN) concentration in the pregnant rats was also determined on various days after uninephrectomy. On fetal days 20 and 22, the glomerular volume was significantly larger in the fetuses from uninephrectomized mothers than in those from sham-operated ones. On fetal day 20, the CF particles were clustered in the laminae rarae interna and externa of the glomerular basement membrane in the fetuses from uninephrectomized mothers, while the clusters were arrayed in three to four layers in the glomerular basement membrane in the fetuses from sham-operated ones. On fetal day 22, the CF particles noted in the lamina rara externa in the fetuses from uninephrectomized mothers were slightly larger in number than such particles in the age-matched control fetuses. The BUN concentration of the uninephrectomized pregnant rats was significantly higher than that of the sham-operated pregnant ones on each postoperative day. These results suggest that the development of the fetal renal glomerulus is accelerated by the elevated BUN level following maternal uninephrectomy when the fetal kidney is functional in effective filtration in the rat. J. Morphol. 238:337–342, 1998. © 1998 Wiley-Liss, Inc.     

The effect of oscillating low intensity magnetic field on the Na+, K+, Ca++, and Mg++ concentrations in the maternal and fetal circulation of the dually perfused human placental cotyledon

Dual-sided perfusions of the human placental cotyledon in vitro were used to study effects of low intensity magnetic fields (MFs) of 2 mT, 50 Hz (E1, 10 perfusions) and 5 mT, 50 Hz (E2, 10 perfusions). In the control group C (10 experiments) no field was used. Perfusions lasted 180 min each. Increased release of calcium ions from the placental cotyledon was found in the fetal circulation during perfusion when the 2 mT, 50 Hz MF was used. No changes in the release of sodium and magnesium ions were observed compared to the control group. The 5 mT, 50 Hz oscillating MF intensified the release of sodium ions from the perfused cotyledon both to the fetal and maternal circulation up to the 150th min of the experiment. Increased release of magnesium ions was observed only to the fetal circulation between 120 and 180 min and of calcium ions to the fetal circulation between 60 and 180 min. No significant differences in K concentrations were found between the control and MF exposed cotyledons under conditions of these experiments.     

Red orange and lemon extract prevents the renal toxicity induced by ochratoxin A in rats

In this work, we investigated the effects of red orange and lemon extract (RLE) on ochratoxin A (OTA)-induced nephrotoxicity. In particular, we analyzed the change in renal function and oxidative stress in Sprague–Dawley rats treated with OTA (0.5 mg/kg body weight, b.w.) and with RLE (90 mg/kg b.w.) by oral administration. After OTA treatment, we found alterations of biochemical and oxidative stress parameters in the kidney, related to a severe decrease of glomerular filtration rate. The RLE treatment normalized the activity of antioxidant enzymes and prevented the glomerular hyperfiltration. Histopathological examinations revealed glomerular damages and kidney cortex fibrosis in OTA-rats, while we observed less severe fibrosis in OTA plus RLE group. Then, we demonstrated that oxidative stress could be the cause of OTA renal injury and that RLE reduces this effect.