Teratogenic Potential of Solenstemma argel Extract in Wistar Albino Rats

The majority of people in Africa receive their basic health care through herbal treatments. Herbal medicine may negatively impact fetal development irreparably. This study examined the teratogenic potential of Solenstemma argel extract in pregnant rats. Pregnant rats were treated with Solenstemma argel from 7th to 16th day of gestation. The dosage used was 250 mg/kg, intraperitoneal.Solenstemma argel extract treated group showed fetal abnormalities appeared as body hemorrhage, limbs abnormalities and resorption of fetuses. These appears in 25% of the fetuses (P-value = 0.01) which is significantly differed from control group. Furthermore, histopathological findings of liver sections from fetuses of Solenstemma argel - treated mothers showed loose liver texture and hepatocytes hemorrhage.In this study, we conclude that the use Solenstemma argel extract during the organogenesis period in pregnant rats has the potential to cause teratogenic effects, as well as abnormalities in liver histopathology.

Acupuncture at ST36 Alleviates the Behavioral Disorder of Autistic Rats by Inhibiting TXNIP-Mediated Activation of NLRP3

Autism is a common neurodevelopmental disorder that severely affects patients’ quality of life. We aimed to investigate whether acupuncture at Zusanli (ST36) could alleviate the behavior disorder of autistic rats by inhibiting thioredoxin-interacting protein (TXNIP)-mediated activation of NLRP3. An autism model was induced by intraperitoneal injection of pregnant rats with valproic acid (VPA). The pups’ behaviors were analyzed using hot plate, open field, Morris water maze, and 3-chamber social interaction tests. Nissl staining was used to visualize neurons in prefrontal cortex. Levels of TXNIP, NLRP3, interleukin (IL)-1β, and caspase were determined by Western blot or quantitative real-time PCR. After ST36 acupuncture, pain sensitivity, autonomous activity, sociability index, sociability preference index, and learning and memory were improved in the autism model rats. Levels of TXNIP, NLRP3, IL-1β, and caspase 1 were decreased after acupuncture. Interference with TXNIP alleviated the behavior disorders and inhibited NLRP3, caspase 1, and IL-1β levels. In summary, ST36 acupuncture reduced TXNIP expression, inhibited the activation of the NLRP3 inflammasome, and alleviated the behavior disorder related to the prefrontal cortex of the autistic rats. These results point to a potential mechanism for acupuncture-induced improvement of autistic behavioral disorders.

The Effect of Quercus infectoria Acorn on Clinical, Hematobiochemical Parameters of Pregnant Albino Rats

Background: Quercus infectoria is a kind of forest tree widely used for livestock feeding within the northern parts of Iraq with little was known about the Quercus infectoria toxicity mainly in pregnant animals. Therefore, this study aimed to investigate the potential effect of Quercus infectoria acorn on the pregnant albino rats. Methods: This study was conducted on the Wistar pregnant rats, using aqueous extract of the acorn at doses of 2 grams/ rat for a period of 10 days. The effect of the quercus acorn on the animal behavior, pregnancy hematobiochemical parameters was investigated compared to the control groups. Result: Neither mortality, nor significant changes in animals’ behavior were detected in treated rats; whereas, abortion and early parturition with lower weight of the pups were observed in treated pregnant rats. Significant increases in red blood cells, packed cell volume, hemoglobin concentration, means corpuscular volume and means corpuscular hemoglobin and levels of neutrophils and eosinophil were reported in treated rats compared to the control groups. Besides, blood urea nitrogen and aspartate aminotransferase were significantly increased in the treated group. Study results suggest that the aqueous extract of Quercus infectoria acorn has potential toxic effects on pregnancy.

Role of heme oxygenase in the regulation of the renal hemodynamics in a model of sex dependent programmed hypertension by maternal diabetes

Intrauterine programming of cardiovascular and renal function occurs in diabetes because of the adverse maternal environment. Heme oxygenase 1 (HO-1) and -2 (HO-2) exert vasodilatory, and antioxidant actions, particularly in conditions of elevated HO-1 expression, or deficient nitric oxide levels. We evaluated whether the activity of the heme-HO system is differentially regulated by oxidative stress in the female offspring of diabetic mothers, contributing to the improved cardiovascular function compared to male. Diabetes was induced in pregnant rats by a single dose of Streptozotocin (STZ, 50mg/kg i.p) in late gestation. Three months old male offspring from diabetic mothers (MOD) exhibited higher blood pressure values (BP), higher renal vascular resistance (RVR), worse endothelium -dependent response to Acetylcholine and an increased constrictor response to Phenylephrine, compared to those in aged matched female (FOD), which were abolished by chronic Tempol (1mM) treatment. In anesthetized animals, Stannous mesoporphyrin (SnMP; 40 µmol/kg i.v.) administration, to inhibit HO activity, increased RVR in FOD and reduced glomerular filtration rate in MOD, without altering these parameters in control animals. Compared to MOD, FOD showed lower nitrotirosyne levels, and higher HO-1 protein expression in renal homogenates. Indeed, chronic treatment with Tempol to MOD, prevented elevations in nitrotyrosine levels, and the acute renal hemodynamics response to SnMP. Then, maternal diabetes results in sex specific hypertension, and renal alterations associated to oxidative stress, mainly in adult male offspring, which are reduced in the female offspring, by elevation in HO-1 expression and lower oxidative stress levels.

Prenatal administration of heparin-binding epidermal growth factor-like growth factor in an experimental model of necrotizing enterocolitis decreased both incidence and severity of the disease

BackgroundNecrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death in premature infants and causes long-term disabilities. Previously, enteral heparin-binding epidermal growth factor-like growth factor (HB-EGF) administered after birth demonstrated decreased incidence and severity of NEC in a neonatal animal model of NEC. We investigated the potential prophylactic strategy of preventing NEC using prenatally administered HB-EGF.MethodsAn HB-EGF (800 µg/kg/dose) dose was injected into pregnant rats via tail vein or intraperitoneal route 2 hours prior to delivery. After cesarean section (C-section) at 21 days’ gestation, the rat pups were subjected to the NEC protocol by inducing stressors: hypoxia, hypothermia, hypertonic feeds, and orogastric gavage of lipopolysaccharide (2 mg/kg). Postnatally, pups were monitored for 96 hours and assessed for the development of clinical and postmortem histological NEC.ResultsThe experimental NEC incidence in untreated, stressed rat pups was 66%. Compared with untreated pups, the maternal administration of HB-EGF correlated with a significant NEC incidence and severity decrease in rat pups. The strongest decrease was seen when HB-EGF was administered via the intraperitoneal route 2 hours prior to C-section (66% vs 31%, *p<0.05). Prenatal HB-EGF administration significantly increased pups’ survival after NEC protocol exposure, with the greatest benefit observed in the group that received HB-EGF intraperitoneally 2 hours before delivery.ConclusionsPrenatal administration of HB-EGF decreases the incidence and severity of NEC, preserves gut barrier function and increases survival. This may represent a novel prophylactic clinical strategy for NEC offered to mothers at risk of delivering a premature infant.

Castor oil Induces Morphological Changes in Endometrium and Biochemical Parameters in Pregnant Wistar Rats

Background: Misoprostol is a synthetic prostaglandin E1 analogue, used for the management of miscarriages and labour. Castor oil is a natural plant extract that has been reported to have some abortifacient Properties Objectives: This study investigated the labour induction and abortifacient properties of castor oil, as well as possible effects on the electrolytes and hormones that regulate pregnancy, as well as to compare these effects with a standard labour inducing drug misoprostol, in Wistar rats. Methods: The study was conducted out in 2 phases. The pregnant rats were administered varying Castor oil doses of low (12.4ml/kg), medium (18.6ml/kg) and high (24.8ml/kg), which were compared with misoprostol group as well as a control group. All animals were euthanized on gestational day 15 and day 20 respectively for the two phases and blood samples collected via cardiac puncture from the apex of the heart for hormonal assay, electrolyte and kidney function tests. The uterus was also removed for histological processing. Results: The abortifacient effect of castor oil is dose dependent with high dose castor oil group seen to have significantly reduced serum progesterone level (32.8±4.25 and 40.8±0.70 compared with 51.0±2.00 of controls), resulted in weight loss and interference with kidney function (increase in serum potassium while decrease in sodium electrolytes). Castor oil also exhibited labor inducing properties. Conclusion: Castor oil has the potential to induce abortion. This study has demonstrated a possible usage of castor oil in medical induction of labor in rats as it exerted uterotonic principle on the uterus.

Effect of Parkia biglobosa seed on lipid profile of dexamethasone-treated pregnant rats

This study was aimed at evaluating the effect of Parkia biglobosa seed on dexamethasone-treated pregnant rats. Locust bean seeds were purchased from an open market in Ado Ekiti, Nigeria. It was processed and ground into powder which was subsequently used in formulating feed for experimental animals. Fifteen female pregnant rats were divided in three groups of five each. Animals in group A were exposed to standard animal feed only. This served as the control group. Those in group B were exposed to animal feed mixed with locust beans + 0.3 mg/kg body weight of dexamethasone, while those in group C were exposed to animal feed mixed with locust beans. At the end of eight days treatment, animals were sacrificed and blood sample was collected into EDTA bottles and centrifuged. Plasma was separated and used for the determination of glucose and lipid profile. Exposure of animals to dexamethasone was observed to significantly (p<0.05) increased the concentration of plasma glucose concentration when compared with the control as well as animals treated with P. biglobosa only. Animals treated with dexamethasone along with P. biglobosa were observed to have higher concentrations of triglyceride, total cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) when compared with those in animals in the control group as well as those treated with P. biglobosa only. Observations from this study revealed that dexamethasone adversely perturbed and unhinged plasma glucose and lipid profile in female pregnant rats while P. biglobosa-formulated diet was observed to be a potent hypoglycemic and hypolipidemic agent.

Morphine Perinatal Exposure Induces Long-Lasting Negative Emotional States in Adult Offspring Rodents

Psychoactive substances during pregnancy and lactation is a key problem in contemporary society, causing social, economic, and health disturbance. In 2010, about 30 million people used opioid analgesics for non-therapeutic purposes, and the prevalence of opioids use during pregnancy ranged from 1% to 21%, representing a public health problem. This study aimed to evaluate the long-lasting neurobehavioral and nociceptive consequences in adult offspring rats and mice exposed to morphine during intrauterine/lactation periods. Pregnant rats and mice were exposed subcutaneously to morphine (10 mg/kg/day) during 42 consecutive days (from the first day of pregnancy until the last day of lactation). Offspring were weighed on post-natal days (PND) 1, 5, 10, 15, 20, 30, and 60, and behavioral tasks (experiment 1) or nociceptive responses (experiment 2) were assessed at 75 days of age (adult life). Morphine-exposed female rats displayed increased spontaneous locomotor activity. More importantly, both males and female rats perinatally exposed to morphine displayed anxiety- and depressive-like behaviors. Morphine-exposed mice presented alterations in the nociceptive responses on the writhing test. This study showed that sex difference plays a role in pain threshold and that deleterious effects of morphine during pre/perinatal periods are nonrepairable in adulthood, which highlights the long-lasting clinical consequences related to anxiety, depression, and nociceptive disorders in adulthood followed by intrauterine and lactation morphine exposure.

Autism-Like Behavior in the Offspring of CYP11A1-Overexpressing Pregnant Rats

Autism spectrum disorders (ASD) represent a complex group of neurodevelopmental disorders that are characterized by impaired social behavior and communication as well as repetitive behavior and restricted interests. Prenatal exposure to high levels of testosterone and preeclampsia are thought to be risk factors of ASD. We had previously reported that overexpression of the mitochondrial cholesterol side-chain cleavage enzyme (CYP11A1) could lead to both preeclampsia-like symptoms and increased testosterone levels in pregnant rats. In this study, we investigated the association between high CYP11A1 levels in pregnant rats and autism-like behavior in their offspring. Timed-pregnant Sprague-Dawley (SD) rats were injected with CYP11A1 gene-carrying adenoviruses on gestational day 8.5, and their offspring were then compared with those from timed-pregnant control SD rats. Compared with their control counterparts, the offspring of the CYP11A1-ovexpressing dams displayed more symptoms of anxiety and spent less time in social interactions and more time in self-grooming and rearing, all indicators of autism-like behavior. Sequencing of the transcriptome in primary microglia from the offspring of CYP11A1-overexpressing dams revealed that immune pathways were highly activated, and the gamma-aminobutyric acid type A (GABAA) receptor genes were among the top differentially expressed genes. Using primary microglia cultures generated from neonatal rats, tumor necrosis factor-alpha expression was found to be elevated in the cells transfected with CYP11A1-carrying adenoviruses. Additionally, the offspring of CYP11A1-overexpressing dams displayed dysregulated GABAA receptor expression. Taken together, these results suggest that abnormal CYP11A1 gene expression in pregnant rats could lead to microglial immune activation and dysregulated GABAA receptor expression in their offspring and thereby anxiety and autism-related behavior. Our study suggests that the pathways regulated by CYP11A1 could be promising preventative and therapeutic targets for ASD.

Preclinical Trial of Traditional Plant Remedies for the Treatment of Complications of Gestational Malaria

Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, a suspension containing a mixture of AI and D.edulis (PS). Aim: This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of Plasmodium falciparum parasite. Method: A predetermined sample size of 30 dams was used (for a power level and confidence interval of 95%), and divided equally into six groups made up of non-malarous dams, untreated malarous dams, and malarous dams either treated exclusively with 1 mL of 3000 mg/kg b.w AI, 1000 mg/kg b.w PS, AI + PS (50% v/v), or 25 mg/kg b.w CQ. Result: No maternal mortality was recorded. AI significantly improved maternal weight gain from 32.4 to 82.2 g and placental weight from 0.44 to 0.53 g. In the curative test, AI and AI + PS significantly reduced the average percentage parasitemia (APP) in the pregnant rats from >80% to <20%. No significant difference in the APP was found between the pregnant rats treated with any of CQ or AI during the suppressive test. Results for the prophylactic test of the study groups showed that the APP was significantly reduced from 24.69% to 3.90% when treated with AI and 3.67% when combined with PS. AI + PS reduced diastolic blood pressure from 89.0 to 81.0 mm/Hg and compared with that of the non malarous dams. AI or AI + PS significantly increased the platelet counts (103 µL) from 214.1 to 364.5 and 351.2, respectively. AI and AI + PS improved birth weight from 2.5 to 3.9 g and crown rump length from 2.6 to 4.1 cm. For biomarkers of preeclampsia, combining AI and PS led to the reversal of the altered levels of creatine kinase, lactate dehydrogenase, cardiac troponin, soluble Fms-Like Tyrosine Kinase-1, and placental growth factor. Conclusions: This study validates the use of A. indica for the treatment of gestational malaria due to its antiplasmodial and related therapeutic effects and in combination with pear seeds for the management of malaria-in-pregnancy-induced preeclampsia.