Adverse Effects In Rats Research Articles

Effects of Increasing Oral Deoxynivalenol Gavage on Growth Performance, Blood Biochemistry, Metabolism, Histology, and Microbiome in Rats.

Mycotoxin-contaminated feed or food can affect physiological responses and cause illnesses in humans and animals. In this study, we evaluated the effects of deoxynivalenol (DON) toxicity on the growth performance, blood biochemistry, histology, microbiome, and metabolism of rats fed with different toxin concentrations. After 1 week of acclimatization, seven-week-old male rats received 0.9% saline as a control, 0.02 mg/kg DON as T1, and 0.2 mg/kg DON as T2 via oral gavage for 4 weeks. The final body weight of the T2 group was significantly lower than that of the control and T1; however, the average daily gain, feed intake, and feed conversion ratio did not differ. Fibrosis and apoptosis were observed in various tissues as DON concentration increased. Creatinine and alkaline phosphatase levels were significantly lower in the DON-treated group than in the control. Firmicutes and Desulfobacterota phyla dominated the cecum, whereas those in the feces were Proteobacteria and Bacteroidetes. Metabolomic profiling showed phenylalanine, tyrosine, and tryptophan biosynthesis as the most prominent pathways. Overall, our results suggest that low-dose and short-term DON exposure can trigger several adverse effects in rats. Dietary toxicants in rats may explain the physiological effects associated with the metabolism commonly reported in animals.

Biocompatibility Study of Purified and Low-Temperature-Sterilized Injectable Collagen for Soft Tissue Repair: Intramuscular Implantation in Rats.

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination. Traditional methods of sterilization (heat and irradiation) can denature collagen. This study addresses these issues by introducing a novel technique: the double filtration and low-temperature steam sterilization of a collagen gel. In vitro tests documented the sterility and confirmed that the collagen did not show cytotoxicity, degradation, integrity, and viscosity characteristics changes after the processing and sterilization. The collagen gel induced new collagen expression and the proliferation of human dermal fibroblasts when the cells were cultured with the collagen gel. An in vivo study found no adverse effects in rats or significant lesions at the implantation site over 13 weeks. These results suggest that this novel method to process collagen gels is a safe and effective skin booster. Advanced processing methods are likely to mitigate the safety risks associated with injectable collagen products, though further research is needed to validate their biological effectiveness and clinical benefits.

Genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2 in Sprague-Dawley rats and Beagle dogs.

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague-Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 109 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials.

A regulatory compliant short-term oral toxicity study of soluble [60]fullerenes in rats.

Thirty-eight years after its discovery, the safety of [60]fullerene (C60), the most abundant fullerene with many potential applications, particularly in oxidative stress-related medicine, remains controversial. This is mainly due to the alleged dangers of C60 nanomaterial, which are regularly supported by some publications. While several academic studies have confirmed the safety of C60 in various experimental models, it is well known that C60 aggregates can carry toxic elements. Meanwhile, countless websites offer C60-oily solutions to consumers, without any regulatory consideration. Therefore, an officially certified toxicity study is urgently needed to avoid any public health problems. In this context, we report on the first certified short-term oral toxicity study of soluble C60, designed according to the guidelines of the Organization for Economic Cooperation and Development, with a deviation in the duration (2 weeks instead of 4 weeks) accepted by the U.S. Food and Drug Administration. The results of this study, conducted in an independent accredited European Laboratory, clearly show that C60 in soluble form (0.8 mg/ml of extra virgin olive oil), administered at the highest possible dose of 3.8 mg/kg body weight/day, did not cause any adverse effects in rats after 14 days of daily oral administration. This report should settle the debate on the acute oral toxicity of C60 and pave the way for further preclinical studies. The study is accompanied by a comprehensive report that includes documentation of the raw data.

Xenogeneic Transplantation Promoted Human Exosome Sequestration in Rat Specific Organs.

Here, we aimed to study the distribution pattern of normal and cancer xenogeneic exosomes (Exos) and possible interspecies reactions in a rat model. Exos were isolated from normal Human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 breast cancer cells. Diameter size and zeta potential distribution were studied using dynamic light scattering (DLS). The morphology of isolated Exos was monitored by scanning electron microscopy (SEM) images. Using western blotting, protein levels of exosomal tetraspanins were detected. For the in vivo study, Dil-labeled normal and cancer Exos were injected into the tail vein (100 µg exosomal protein/rat) three times at 1-hour intervals. After 24 hours, rats were euthanized and the cellular uptake of Exos was monitored in different organs using immunofluorescence staining (IF). The size distribution and mean zeta potential of HUVEC and MDA-MB-231 cells Exos were 80±29.94 and 64.77±25.49 nm, and -7.58 and -11.8 mV, respectively. Western blotting revealed CD9, CD81, and CD63 in normal and cancer Exos. The SEM images exhibited typical nano-sized round-shape Exo particles. IF staining indicated sequestration of administrated Exos in splenic tissue and lungs. The distribution of Exo in kidneys, aorta, and hepatic tissue was less. These features were more evident in the group that received cancer Exos. We found no obvious adverse effects in rats that received normal or cancer Exos. Normal and cancerous xenogeneic human Exos can be sequestrated prominently in splenic tissue and lungs. Novel delivery approaches and engineering tools are helpful in the target delivery of administrated Exos to the injured sites.

Cytotoxicity, acute and sub-chronic toxicities of the leaves of Bauhinia thonningii (Schumach.) Milne-Redh. (Caesalpiniaceae)

BackgroundBauhinia thonningii is a plant traditionally used against many human diseases such as gastric ulcers, fever, inflammations, coughs, dysentery, diarrhea, and malaria. In the present investigation, the cytotoxicity of methanol extract of Bauhinia thonningii leaves (BTL), fractions and the isolated phytoconstituents was determined in a panel of 9 human cancer cell lines including drug sensitive and multidrug-resistant (MDR) phenotypes. The acute and sub-chronic oral toxicity of BTL was investigated as well.MethodsCompounds were isolated using chromatographic techniques while their chemical structures were determined using spectroscopic methods. The resazurin reduction assay (RRA) was used to evaluate the cytotoxicity of samples, propidium iodide (PI) for apoptosis, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining for mitochondrial membrane potential (MMP) analysis, 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining for the quantification of reactive oxygen species (ROS), whereas Caspase Glo assays were combined by means of flow cytometry. Furthermore, the toxicological investigations were performed as recommended by the Organization for Economic Cooperation and Development (OECD).ResultsThe botanicals as well as 6-C-methylquercetin-3,7-dimethyl ether (2), quercetin-3-O-L-rhamnopyranoside (5), quercetin-3-O-β-glucopyranoside (6), 6,8-C-dimethylkaempferol 3,7-dimethyl ether (7), and 6,8-C-dimethylkaempferol-3-methyl ether (8) had promising cytotoxic effects in the 9 tested cancer cell lines. The IC50 values below 20 µg/mL (botanicals) or 10 µM (compounds) on at least 1/9 tested cancer cell lines were considered. The best cytotoxic effects with IC50 values below 5 µM were achieved with compounds 7 against CEM/ADR5000 leukemia cells (2.86 µM) and MDA-MB-231-pcDNA breast adenocarcinoma cells (1.93 µM) as well as 8 against CCRF-CEM leukemia cells (3.03 µM), CEM/ADR5000 cells (2.42 µM), MDA-MB-231-pcDNA (2.34 µM), and HCT116 p53−/− cells (3.41 µM). BTL and compound 8 induced apoptotic cell death in CCRF-CEM cells through caspase activation, alteration of MMP, and increased ROS production. BTL did not cause any adverse effects in rats after a single administration at 5000 mg/kg or a repeated dose of 250 mg/kg body weight (b. w.).ConclusionBauhinia thonningii and its constituents are sources of cytotoxic drugs that deserve more in-depth studies to develop novel antiproliferative phytomedicine to fight cancer including resistant phenotypes.

Toxicity Test on the Combination of Caesalpinia sappan and Zingiber officinale in Rattus norvegicus Induced by Complete Freund's Adjuvant

Highlights:1. This study determined the toxic effects of combining Caesalpinia sappan and Zingiber officinale extracts, aspeople need to be aware of the potential side effects of these common herbal remedies for the treatment ofrheumatoid arthritis.2. The combination of Caesalpinia sappan and Zingiber officinale extracts is efficacious and non-toxic as an antiarthritis treatment, hence, the ingredients can be upgraded to standardized herbal medicines andphytopharmaceuticals. Abstract Sappanwood (Caesalpinia sappan) and red ginger (Zingiber officinale) are plant species that have been studied for theirefficacy in treating inflammation related to rheumatoid arthritis. This study aimed to examine the effects of combiningsappanwood and red ginger in order to determine the potential toxicity of the herbal extracts in medicine. The toxicitytesting was carried out in vivo using 32 Wistar strain male white rats (Rattus norvegicus) grouped into eight groups of four.The rats were injected with complete Freund's adjuvant to induce a chronic inflammatory effect. The eight groups consistedof the negative control group, the positive control group, the normal group, and five treatment groups. This study wasconducted by observing the animals for toxic symptoms and death to determine the safety of the extracts and drugs. Theobservation results were analyzed using a one-way analysis of variance (p<0.05). The analysis results showed that weightgain and relative organ weight among the groups had no significant differences (p>0.05). Microscopic examination of theorgan preparations observed under a light microscope revealed no significant changes or adverse effects in rats treated withthe extracts or drugs. In conclusion, a combination of sappanwood and red ginger ethanol extracts administered orally hasno toxic effect in rats injected with complete Freund's adjuvant.

Oral mometasone furoate administration preserves anti-inflammatory action with fewer metabolic adverse effects in rats

BackgroundExogenous glucocorticoids (CGs) possess relevant therapeutic effects but exert diabetogenic actions when in excess. Thus, ligands with potential therapeutic applications and fewer adverse effects are needed. To this, we analyzed whether mometasone furoate (MF), a CG expected to cause fewer side effects, given through systemic routes, could maintain the anti-inflammatory actions without relevant repercussions on metabolism. MethodsThe anti-inflammatory effect of MF was evaluated with both peritonitis and colitis models in rodents. Glucose and lipid metabolism were investigated in male and female rats treated daily with MF with different doses and routes of administration for seven days. The involvement of glucocorticoid receptor (GR) on MF actions was assessed in animals pretreated with mifepristone. Also, the potential reversibility of the adverse effects was assessed. Dexamethasone was used as a positive control. ResultsMF treatment resulted in glucose intolerance in male rats treated through intraperitoneal (ip) but not oral gavage route (og). In female rats, none of the routes led to glucose intolerance. MF treatment attenuated insulin sensitivity and increased pancreatic β-cell mass, regardless of the sex and route of administration. MF treatment through og route did not result in dyslipidemia, as observed in rats treated through the ip route (both sexes). The anti-inflammatory and metabolic adverse effects of MF were GR-dependent, and metabolic outcomes altered by MF administration were reversible. ConclusionMF maintains anti-inflammatory activity when administered by systemic routes and exerts less impact on metabolism when administered orally in male and female rats, effects that are GR-dependent and reversible.Category: Metabolic Disorders and Endocrinology.

Toxicological Evaluation of Alginic Acid, a Polysaccharide Isolated from <i>Turbinaria conoides</i> (J. Agardh) Kutzing on Wistar Albino Rats

Introduction: Alginic acid, a polysaccharide is one of the important phytochemical ingredients of brown algae, Turbinaria conoides (J. Agardh) Kutzing. T. conoides has been studied for various pharmacological activities, yet no toxicological information found in the literature therefore, preset study aimed at extraction and isolation of alginic acid and to assess the safety profile through acute and sub acute toxicity study in both male and female rats. Materials and Methods: Alginic acid was characterized through Fourier transform infrared spectroscopy, thermo gravimetric and differential scanning calorimetric analysis. In acute toxicity study, female rats received 2000 mg/kg of isolated product, at a single dose on oral administration. In subacute toxicity study, both male and female rats were given with 100, 200 and 400 mg/kg of the isolated product, orally, for a period of 28 days consecutively and behavioral changes, hematological, biochemical and histopathological investigations were verified. Results and Discussion: In acute toxicity study, no morbidity or mortality was reported with alginic acid treated animals at a dose of 2000 mg/kg. In sub-acute toxicity study, there were no treatment related abnormalities observed in hematological and biochemical parameters except, decreased red blood cell count (400 mg/kg); increased platelets (200 mg/kg) in female rats and increased levels of liver parameters (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma glutaryl transferase); lipid parameters (total cholesterol, triglycerides and blood glucose) in both male and female rats. Histopathology studies revealed a slight infiltration of cells and congestion in blood vessels in the liver; congestion of alveolar tissue in lungs with 400 mg/kg treated animals. No behavioural changes observed. Conclusion: From the obtained results it is indicated that the oral administration of alginic acid (active principle of T. conoides) did not produce any significant adverse effects in rats of both the sex. Hence, alginic acid was considered as safe to use for further therapeutic purpose.

Synthesis, characterization, and in vivo safety evaluation of propylated Dioscorea abyssinica starch.

The use of starch, a natural polymeric material, and derivatives thereof is based on its adhesive, thickening, gelling, swelling, and film-forming properties, as well as its ready availability. The objective of this research work is to develop an effective propylated Dioscorea abyssinica starch (PDAS) as a hydrophobic excipient for pharmaceutical applications with a reasonable price. This paper reports on the synthesis, characterization, and in vivo safety evaluation of PDAS. Native Dioscorea abyssinica starch (NDAS) was modified to its propylated form with propionic anhydride and characterized. Crystallinity, morphological structure, thermal behavior, solubility, and safety of PDAS were evaluated using x-ray diffraction, SEM, thermogravimetric, gravimetric, and toxicity studies, respectively. Propionyl content and degree of substitution (DS) of starch increased significantly (p < 0.05) with an increase in reaction time and temperature. Propionyl content and DS of starch increased significantly (p < 0.05) with a decrease in the ratio of starch to pyridine and starch to propionic anhydride in the reaction medium. FTIR spectra of PDAS indicated that hydroxyl groups participated in the propylation reaction. X-ray diffraction results showed that the chemical modification destroyed the crystalline structure of the NDAS. SEM of NDAS showed a rounded shape which became irregular after propylation. Thermogravimetric curves revealed that all the PDAS samples decomposed at higher temperatures than their native counterparts. At higher DS, swelling power and solubility in an aqueous environment significantly (p < 0.05) decreased below that of the native starch. PDAS with high DS, were soluble in organic solvents at room temperature. But PDAS with lower DS didn't dissolve in all types of organic solvents used. PDAS (DS = 2.842) in distilled water did not produce adverse effects in rats. Based on the results obtained, it can be concluded that PDAS can be considered as a generally safe excipient and fulfills the physicochemical properties of a hydrophobic excipient.

Therapeutic Targeting Notch2 Protects Bone Micro-Vasculatures from Methotrexate Chemotherapy-Induced Adverse Effects in Rats.

Intensive cancer chemotherapy is well known to cause bone vasculature disfunction and damage, but the mechanism is poorly understood and there is a lack of treatment. Using a rat model of methotrexate (MTX) chemotherapy (five once-daily dosses at 0.75 mg/kg), this study investigated the roles of the Notch2 signalling pathway in MTX chemotherapy-induced bone micro-vasculature impairment. Gene expression, histological and micro-computed tomography (micro-CT) analyses revealed that MTX-induced micro-vasculature dilation and regression is associated with the induction of Notch2 activity in endothelial cells and increased production of inflammatory cytokine tumour necrosis factor alpha (TNFα) from osteoblasts (bone forming cells) and bone marrow cells. Blockade of Notch2 by a neutralising antibody ameliorated MTX adverse effects on bone micro-vasculature, both directly by supressing Notch2 signalling in endothelial cells and indirectly via reducing TNFα production. Furthermore, in vitro studies using rat bone marrow-derived endothelial cell revealed that MTX treatment induces Notch2/Hey1 pathway and negatively affects their ability in migration and tube formation, and Notch2 blockade can partially protect endothelial cell functions from MTX damage.

Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer.

Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10B-labeled BPA (10B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague–Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue.

Toxicological Studies of Hydroethanolic Leaf Extract of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) on Wistar Rats

Introduction: The impact of aromatic plants used in cooking on health is indisputable.&#x0D; This study aims to evaluate the in vitro cytotoxicity of Artemia salina, acute and the 28 days subchronic toxicity of X. aethiopica dried fruit used like spice in Togo by oral administration of the extract to female Wistar rats.&#x0D; Results: The A. salina assay showed that the hydroalcoholic extract of X. aethiopica presented any toxicity. The LC50 values of X. aethiopica on brine shrimp were 0.64 ± 0.13 mg/mL. The acute toxicity study revealed neither behavioral disturbances nor death in rats. The lethal dose (DL50) of this extract is greater than 5000 mg/kg body weight. The results of subchronic toxicity showed no significant change in body and organs weight gain in rats at test doses throughout the treatment period. No changes in haematological parameters were observed apart from a significant increase in platelet number at doses of 500 and 1000 mg/kg. Biochemical parameters such as Urea, Creatinine, Triglycerides, Total cholesterol, Serum glutamic pyruvic transaminase (SGPT), C-reactive protein (CRP) and glycemia were not significantly changed. Serum glutamic oxaloacetic transaminase (SGOT) and Alkaline phosphatase (ALP) activities increased at doses of 500/1000 mg/kg and 1000 mg/kg respectively. Creatine Phosphokinase (CPK) activity decrease at the dose of 500 and 1000 mg/kg. Blood electrolytes showed no significant change. The histological sections showed no organ damage.&#x0D; Conclusions: Aqueous extract of X. aethiopica did not lead to any adverse effects in rats after acute and subchronic treatment at 500 and 1000 mg/kg doses. &#x0D; Keywords: Xylopia aethiopica, Cytotoxicity, Toxicity, Wistar rats.

In-vitro and in-vivo toxicological studies of hydroethanolic leaf extract of Ocimum gratissimum Linn. (Lamiaceae) in Wistar rats

Herbal medicines have been used for human health management, prevention, and cure of human diseases since ancient civilizations. In recent days, the use of herbal medicines has increased significantly in various forms such as herbal formulations, dietary supplements, and nutraceuticals in the global market. This growing demand undoubtedly improves the therapeutic claims of herbal medicines as biomedicines and/or functional foods. However, the safe use of herbal products and herbal drugs remains a challenge due to toxicity and regulatory issues. This study aims to evaluate the cytotoxicity of hydroethanolic leaf extract of Ocimum gratissimum on the larvae of Artemia salina in vitro and in-vivo acute and subchronic toxicity study in Wistar rats. The test on A. salina showed that the hydroalcoholic extract of O. gratissimum did not show any toxicity. The LC50 values of O. gratissimum on brine shrimp were 0.60 ± 0.19 mg/ml. The acute toxicity study revealed no behavioral disturbances or death in rats. The extract lethal dose (LD50) is greater than 5000 mg/kg body weight. Subchronic toxicity results showed a significant increase in abdominal fat at 1000 mg/kg. As for the hematological parameters, there was a significant decrease in the number of platelets at doses of 500 and 1000 mg/kg. Some biochemical parameters were affected by repeated administration of O. gratissimum extract for 28 days. Alkaline phosphatase (ALP) activity was increased at 500 and 1000 mg/kg. Creatine phosphokinase (CPK) and urea decreased at 500 and 1000 mg/kg, respectively. Blood electrolytes showed no significant change. Histological sections showed no organ damage. In conclusion, aqueous extract of O. gratissimum caused no adverse effects in rats after acute and subchronic treatment at 500 and 1000 mg/kg. However, specific hematological and biochemical parameters should be monitored during chronic use. Keywords: Ocimum gratissimum, cytotoxicity, toxicity, Wistar rats.

Perinatal exposure to the thyroperoxidase inhibitors methimazole and amitrole perturbs thyroid hormone system signaling and alters motor activity in rat offspring

Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by inhibiting the thyroperoxidase (TPO) enzyme, which is key to thyroid hormone synthesis. For the potent TPO-inhibiting drug propylthiouracil (PTU) this has been shown to result in thyroid hormone system disruption and altered brain development in animal studies. However, an outstanding question is which chemicals beside PTU can cause similar effects on brain development and to what degree thyroid hormone insufficiency must be induced to be able to measure adverse effects in rats and their offspring. To start answering these questions, we performed a perinatal exposure study in pregnant rats with two TPO-inhibitors: the drug methimazole (MMI) and the triazole herbicide amitrole. The study involved maternal exposure from gestational day 7 through to postnatal day 22, to MMI (8 and 16 mg/kg body weight/day) or amitrole (25 and 50 mg/kg body weight/day). Both MMI and amitrole reduced serum T4 concentrations in a dose-dependent manner in dams and offspring, with a strong activation of the hypothalamic-pituitary-thyroid axis. This reduction in serum T4 led to decreased thyroid hormone-mediated gene expression in the offspring’s brains and caused adverse effects on brain function, seen as hyperactivity and decreased habituation in preweaning pups. These dose-dependent effects induced by MMI and amitrole are largely the same as those observed with PTU. This demonstrates that potent TPO-inhibitors can induce effects on brain development in rats and that these effects are driven by T4 deficiency. This knowledge will aid the identification of TPO-inhibiting thyroid hormone system disruptors in a regulatory context and can serve as a starting point in search of more sensitive markers of developmental thyroid hormone system disruption.

Effects of soy hull polysaccharide on dyslipidemia and pathoglycemia in rats induced by a high-fat-high-sucrose diet

The present work aimed at investigating the effects of soy hull polysaccharide (SHP) in alleviating adverse effects in rats fed a high-fat-high-sucrose diet. After SHP feeding for 4 weeks, the fasting blood glucose (FBG), serum triglyceride (TG), serum high-density lipoprotein cholesterol (HDL-C), short chain fatty acids (SCFAs), and 16S rDNA gene sequence were determined. Administration of SHP significantly decreased body fat content and TG levels, and increased water intake and HDL-C levels after 4 weeks of treatment. The antihyperglycemic effect of SHP at a dose of 400mg/kg mb had the most significant effects among the three dosage groups. SHP notably restored the FBG in rats fed a high-fat-high-sucrose diet (P<0.05). Furthermore, SHP at 400mg/kg mb increased the abundance of Bacteroidetes and decreased that of Firmicutes and Actinobacteria at the phylum level. The polysaccharide treated groups had significantly higher content of total SCFAs, and the main fermentation products were acetic, propionic, n-valeric and i-valeric acids. Thus, SHP restores blood lipid levels in rats fed a high-fat-high sucrose diet through regulation of the gut microbiota.

Safety evaluation and hypolipidemic effect of aqueous-ethanol and hot-water extracts from E Se tea in rats

E Se tea, processed by the fresh leaves of Malus toringoides (Rehd.) Hughes, is a traditional herbal tea with various human benefits. The present study was aimed to evaluate the toxicity and hypolipidemic effect of aqueous-ethanol extract (EE) and hot-water extract (WE) from E Se tea. Eight main chemical constituents in EE and WE were respectively identified and quantified by UHPLC-HRMS/MS. EE is rich in TPC and TFC, while WE had higher TPS content. Both EE and WE exhibited strong antioxidant activity with no significant difference. The acute toxicity study revealed that the LD50 values were higher than 5000 mg/kg, while both WE and EE had no significant adverse effect in rats by subacute toxicity assay. However, the triglyceride (TG) content in experiment groups (male) and highest doses groups (female) significantly decreased. Furthermore, the hypolipidemic effect of WE and EE were performed on high fat diet induced hyperlipidemic rats. The result exhibited that either WE or EE could effectively regulate lipid droplet accumulation in liver, and reduce the adipocyte size. These results demonstrated that these two extracts from E Se tea could be regarded as a potential functional dietary supplement in preventing and treating diet induced metabolic diseases.

Safety assessment of phytase transgenic maize 11TPY001 by 90-day feeding study in rats

11TPY001 is a transgenic maize that expresses the Aspergillus niger phyA2 gene which could significantly improve phosphorus bioavailability in monogastric animals. The present study was conducted to investigate the potential health effects of phytase transgenic maize 11TPY001 through a 90-day subchronic rodent feeding study. Maize grains from 11TPY001 or its parental counterpart maize OSL963 were incorporated into rodent diets at 12.5%, 25% and 50% concentrations by mass and administered to Sprague-Dawley rats (n = 10/sex/group) for 90 days. An additional control group of rats (n = 10/sex/group) were fed with common maize Zhengdan958 diets at 50% by mass. All formulated diets were nutritionally balanced. Body weights, food intake, hematology, serum chemistry, absolute and relative organ weights were measured, and gross as well as microscopic pathology were examined. Compared with rats fed OSL963 maize and the common maize diet groups, no adverse diet-related differences were observed in rats fed 11TPY001 maize diets with respect to clinical signs of toxicity, body weight/gain, food consumption/efficiency, hematology, clinical chemistry, organ weights, and gross and microscopic pathology. Under the conditions of this study, the results indicated that 11TPY001 did not cause any treatment related adverse effects in rats compared with its non-transgenic parental maize OSL963.

Toxicological Profile of the Aqueous Extract of Tectona grandis L.F. (Verbenaceae) Leaves: A Medicinal Plant Used in the Treatment of Typhoid Fever in Traditional Cameroonian Medicine

Tectona grandis (T. grandis) is a medicinal plant widely used in Cameroon to treat typhoid fever and several other diseases. Despite its heavy use for medical purposes, no study has yet been conducted to assess its potentially toxic effects. This study aimed at evaluating the acute and subchronic toxicological profile of Tectona grandis leaf extract in rats. The acute toxicity study revealed neither behavioral disturbances nor death in rats. The lethal dose (DL50) of this extract is greater than 5000 mg/kg body weight. The subchronic toxicity study showed no significant change in weight gain in rats at test doses throughout the treatment period. However, there was a significant decrease in alanine transaminase activity and serum protein levels at all doses. Alkaline phosphatase activity decreased at doses of 30, 90, and 270 mg/kg and increased at the dose of 810 mg/kg body weight. Serum and urinary urea levels increased simultaneously at doses of 270 and 810 mg/kg body weight. Repeated administration of the extract also increased total cholesterol, high-density lipoprotein levels in both sexes were compared to respective controls, and the ratio of high- to low-density lipoprotein was found to be greater than 1 in all animals. However, at the dose of 810 mg/kg, necrosis was observed on the kidney sections and vascular congestion on the liver sections of animals. Aqueous extract of T. grandis did not lead to any adverse effects in rats after acute and subchronic treatment at 30 and 90 mg/kg doses. This extract can, therefore, be used for the formulation of typhoid fever phytomedicine at the therapeutic dose of 30 mg/kg, but before this, chronic and mutagenic toxicity evaluations must be carried out.

Acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii (Miq.) Miq. stem bark in rats

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.