scholarly journals A Pathology Review of the Lower Gastrointestinal Tract in Relation to Ulcerative Colitis in Rats and Cynomolgus Macaques Treated With Ammonium Perfluorooctanoate

2020 ◽  
Vol 48 (4) ◽  
pp. 593-602 ◽  
Author(s):  
Sue Chang ◽  
George A. Parker ◽  
Sarah E. Kleinschmidt ◽  
Geary W. Olsen ◽  
Carol A. Ley ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gastrointestinal Tract ◽  
Laboratory Animals ◽  
Ohio River ◽  
Positive Trend ◽  
Sprague Dawley ◽  
Toxicological Studies ◽  
Chronic Inflammatory Condition ◽  
Cynomolgus Macaques ◽  
Rigorous Treatment

Among many short-term, subchronic, and chronic toxicology studies with ammonium perfluorooctanoate (PFOA), the gastrointestinal tract has not been identified as a target organ for PFOA-related toxicity in laboratory animals where the corresponding serum PFOA concentrations typically approach several orders of magnitude higher than the general human population. These lack of gastrointestinal tract-related findings were in direct contrast to an epidemiological observation where a positive trend was observed for ulcerative colitis, an idiopathic chronic inflammatory condition of the gut, in a Mid-Ohio River community whose drinking water contained higher levels of PFOA. This study was conducted to perform a histological reevaluation of large intestine sections in laboratory animals from 2 long-term toxicological studies: one was with Sprague Dawley rats that received ammonium PFOA in their diet for 2 years and the other one was with cynomolgus macaques that received daily capsules of ammonium PFOA for 6 months. In both studies, there was a lack of histological evidence of treatment-related inflammatory lesions that was suggestive of the occurrence of ulcerative colitis in these laboratory animals even under the most rigorous treatment schedules. These findings do not offer support for the biological plausibility of the epidemiological associations reported.

scholarly journals Development and Validation of an Analytical Method for Quantitation of Monobutylphthalate, a Metabolite of Di-n-Butylphthalate, in Rat Plasma, Amniotic Fluid, Fetuses and Pups by UPLC-MS/MS

2020 ◽  
Vol 44 (4) ◽  
pp. 370-377 ◽  
Author(s):  
Melanie A Rehder Silinski ◽  
Reshan A Fernando ◽  
Veronica G Robinson ◽  
Suramya Waidyanatha
Keyword(s):  
Amniotic Fluid ◽  
Endocrine System ◽  
Rat Plasma ◽  
Consumer Products ◽  
Negative Ion ◽  
Laboratory Animals ◽  
Sprague Dawley ◽  
Simple Method ◽  
Toxicological Studies ◽  
Relative Standard

Abstract Phthalates have been used for decades as softening agents in the production of plastics, but in recent years have been extensively investigated for their potential hazards to human health and the environment. Di-n-butyl phthalate (DBP), with widespread exposure occurring through a variety of consumer products such as cosmetics and pesticides, is a suspected carcinogen and an endocrine system disruptor in both humans and laboratory animals. Its predominant metabolite is the monoester, monobutyl phthalate (MBP), which can serve as a marker of exposure. To support toxicological studies of DBP in pregnant and lactating rats and their offspring, a novel ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for quantitation of MBP in rat plasma, amniotic fluid, fetuses and whole pup samples. Plasma samples were extracted using a simple protein precipitation with acetonitrile. Extraction and delipidation of pup homogenate was performed using acetonitrile and then submerging the vials in liquid nitrogen. Extracts were analyzed by UPLC-MS/MS in the negative ion mode. The method was successfully validated over the concentration ranges 25–5,000 ng/mL in female Sprague Dawley (SD) rat plasma and 50–5,000 ng/g in SD pup homogenate. Matrix calibration curves were linear (r ≥ 0.99), and the percent relative error (%RE) values were ≤ ±15% for standards at all levels. Absolute recoveries were > 92% in both matrices. The limits of detection (LODs) were 6.9 ng/mL in plasma and 9.4 ng/g in pup homogenate. Acceptable intra- and interday accuracy and precision were demonstrated by mean %RE ≤ ±7.5 and relative standard deviation (%RSD) ≤ 10.1%. Extract stability was demonstrated for ~6 days at various temperatures and freeze–thaw stability was demonstrated after 3 cycles over 3 days. Secondary matrix evaluation was performed for MBP in amniotic fluid and pooled fetus homogenate (mean %RE ≤ ±11.5 and %RSD ≤ 13.7). These data demonstrate that this simple method is suitable for determination of MBP in plasma, amniotic fluid, fetus and pup samples from toxicological studies of DBP.

scholarly journals The POTENTIAL OF CAESALPINIA CRISTA LEAVES IN THE TREATMENT OF ULCERATIVE COLITIS IN LABORATORY ANIMALS

2018 ◽  
Vol 8 (5) ◽  
pp. 374-381
Author(s):  
Bharati Zaware ◽  
Ritu Gilhotra ◽  
Sanjay Chaudhari
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Acetic Acid Solution ◽  
Ethanol Extract ◽  
Experimental Colitis ◽  
Laboratory Animals ◽  
Sprague Dawley ◽  
Ulcer Index ◽  
Standard Drug ◽  
Sprague Dawley Rats

The aim of present investigation was to study the Ulcerative colitis effect of extracts of Caesalpinia crista in acetic acid induced experimental colitis in Sprague Dawley rats. Sprague Dawley rats were divided into nine groups (n=6). The rats were received 7 days pretreatment with chloroform, ethyl acetate, ethanolic extracts of C. crista 200 mg/kg and 400 mg/kg. Ulcerative colitis was induced by intrarectal administration of 1ml of 4% acetic acid solution on 8th day. Prednisolone (2 mg/kg) was used as standard drug administered orally for 3 days. After 48 hrs of colitis induction animals were sacrificed by cervical dislocation to remove colon and distal 5 cm of the colon was dissected. Macroscopical study, Ulcer index of the colon, colonic myeloperoxidase (MPO) and malondialdehyde (MDA) level in colon tissue and blood were studied. Intrarectal instillation of acetic acid caused enhanced ulcer index, myeloperoxidase and malondialdehyde. Ethanol extract of C.crista showed significant effect in lowering ulcer index as well as neutrophil infiltration at a dose of 400 mg/kg in acetic acid induced colitis. The present investigation demonstrates that the ethanol extract of C.crista is of potent therapeutic value in the amelioration of experimental colitis in rat by inhibiting the inflammatory mediator.

Actual issues of hygienic regulation and creation of safe working conditions at pharmaceutical manufacturing enterprises

2020 ◽  
Vol 60 (10) ◽  
pp. 640-644
Author(s):  
Vadim M. Vasilkevich ◽  
Ruslan V. Bogdanov ◽  
Elena V. Drozdova
Keyword(s):  
Pharmaceutical Industry ◽  
Working Conditions ◽  
Experimental Studies ◽  
Pharmaceutical Products ◽  
Laboratory Animals ◽  
Production Environment ◽  
Basic Principles ◽  
Toxicological Studies ◽  
Health Disorders ◽  
Safe Working

Introduction. The working conditions of pharmaceutical industry workers are characterized by the combined effect of unfavorable factors of the production environment, among which the leading one is chemical. The aim of study is to substantiate the basic principles and criteria for hygienic regulation of pharmaceutical products in their production to ensure safe working conditions for employees based on the results of their own research and existing requirements of technical regulations. Materials and methods. Analysis of working conditions and the prevalence of health disorders in pharmaceutical workers (according to literature data), toxicological studies of pharmaceutical substances on laboratory animals, scientific justification of hygiene standards in the air of the working area. Results. Among employees of the pharmaceutical industry, the predominant forms of production-related health disorders are diseases of the respiratory system, as well as skin dermatitis of allergic origin, liver and biliary tract diseases. Based on the results of experimental studies of domestic pharmaceutical products for the treatment of cardiovascular, oncological and mental diseases that have priority socio-economic significance, the basic principles and features of the practice of justifying the hygienic standards of medicines in the air of the working area are developed and systematized. Conclusions. During hygienic rationing of medicines, it is necessary to use a differentiated approach that allows, based on the analysis of information about the chemical structure, physical and chemical characteristics, production conditions, pharmacotherapeutic activity, and the results of studying the toxic effect in an experiment on laboratory animals, to determine the maximum permissible content in the air of the working area of medicines or to justify the prohibition of isolation with reasoned recommendations for their safe production.

scholarly journals Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food

2021 ◽  
Vol 18 (7) ◽  
pp. 3332
Author(s):  
Olga V. Naidenko ◽  
David Q. Andrews ◽  
Alexis M. Temkin ◽  
Tasha Stoiber ◽  
Uloma Igara Uche ◽  
...  
Keyword(s):  
Immune System ◽  
High Throughput ◽  
Environmental Protection Agency ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Specific Activity ◽  
Laboratory Animals ◽  
In Vitro Assays ◽  
Toxicological Studies

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

scholarly journals Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Robin Mesnage ◽  
Maxime Teixeira ◽  
Daniele Mandrioli ◽  
Laura Falcioni ◽  
Mariam Ibragim ◽  
...  
Keyword(s):  
Stress Response ◽  
Microbial Community Composition ◽  
Serum Biochemistry ◽  
Feed Consumption ◽  
Laboratory Animals ◽  
Toxicity Tests ◽  
Sprague Dawley ◽  
Shotgun Metagenomics ◽  
Low Concentrations ◽  
Sprague Dawley Rats

AbstractHealth effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants.

Lactobacillus acidophilus and Clostridium butyricum ameliorate colitis in murine by strengthening the gut barrier function and decreasing inflammatory factors

2018 ◽  
Vol 9 (5) ◽  
pp. 775-787 ◽  
Author(s):  
Y. Wang ◽  
Y. Gu ◽  
K. Fang ◽  
K. Mao ◽  
J. Dou ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Lactobacillus Acidophilus ◽  
Barrier Function ◽  
Clostridium Butyricum ◽  
In Vivo Studies ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Barrier Function ◽  
Anti Inflammatory

Ulcerative colitis is a type of chronic inflammation present in the intestines for which the aetiology is not yet clear. The current therapies for ulcerative colitis cannot be considered to be long-term management strategies due to their significant side effects. Therefore, it is essential to identify an alternative therapeutic strategy for ulcerative colitis. The present study focused on the evaluation of the anti-inflammatory activities of Lactobacillus acidophilus CGMCC 7282 and Clostridium butyricum CGMCC 7281. The roles of both single and combination of L. acidophilus CGMCC 7282 and C. butyricum CGMCC 7281 in ulcerative colitis were investigated in 2,4,6-trinitrobenzenesulfonic acid-induced acute colitis (Th1-type colitis) in Sprague-Dawley rats and oxazolone-induced chronic colitis (Th2-type colitis) in BALB/c mice. The in vivo studies showed that the administration of L. acidophilus CGMCC 7282, C. butyricum CGMCC 7281 and L. acidophilus CGMCC 7282 plus C. butyricum CGMCC 7281 could reduce the Th1-type colitis as well as the Th2-type colitis, and the combination of the two strains exhibited the most notable effects, as indicated by the reduced mortality rates, the suppressed disease activity indices, the improved body weights, the reduced colon weight/colon length and colon weight/body weight ratios, and the improved gross anatomic characteristics and histological features (ameliorations of neutrophil infiltration and ulceration in the colon). It was found that the alterations of the gut microbiome, the barrier function changing and the selected inflammation-related cytokines are observed in the ulcerative colitis rats/mice treated with L. acidophilus CGMCC 7282 and C. butyricum CGMCC 7281. The combination of L. acidophilus CGMCC 7282 plus C. butyricum CGMCC 7281 also exerted a stronger anti-inflammatory effect than either of the single strains alone in vitro. These findings provide evidence that the administration of L. acidophilus CGMCC 7282 plus C. butyricum CGMCC 7281 may be a promising therapy for ulcerative colitis.

scholarly journals Histomorphologic Analysis of the Late-term Rat Fetus and Placenta

2018 ◽  
Vol 46 (2) ◽  
pp. 158-168 ◽  
Author(s):  
Phanie L. Charest ◽  
Vanessa Vrolyk ◽  
Pauline Herst ◽  
Maryse Lessard ◽  
Deborah M. Sloboda ◽  
...  
Keyword(s):  
Cutting Planes ◽  
Whole Body ◽  
Future Research ◽  
Serial Sectioning ◽  
Sprague Dawley ◽  
Rat Fetus ◽  
Rat Fetuses ◽  
Toxicological Studies ◽  
Hematoxylin Eosin ◽  
Gross Examination

Histological examination of the rat placenta and fetus is uncommon. Toxicological studies mainly rely on gross examination of the fetus and on fetal and placental weights. These are often insufficient to assess the fetal and placental toxicity of xenobiotics. The small size of the fetus makes its dissection labor-intensive. Thus, our objective was to develop a simple and accurate technique to evaluate the rat fetus and placenta. Sprague-Dawley rat fetuses at gestational day 19.5 ( n = 18) and their placentas ( n = 32) were fixed in formalin. Placentas were cut transversally in the center. Fetuses were cut following a freehand whole-body serial sectioning diagram adapted from Wilson’s method. Sections were stained with hematoxylin–eosin–phloxine–saffron, and histomorphometry was used to measure the area of the fetal placental region (27.2 ± 1.7 mm2), including the labyrinth (22.2 ± 1.0 mm2) and the basal zone (4.8 ± 0.8 mm2). Our whole-fetus serial sectioning technique resulted in 12 precise cutting planes that fit on 3 histological slides, enabling the examination of most organs without labor-intensive dissection. Quantitative analysis of placental areas improves the understanding of the pathogenesis of treatment-related changes. This technique provides a standardized method for future research in pertinent fields such as developmental biology and toxicology.

Study of toxicity and peculiarities of biological effects of nanocomposite pectin-Ag: results of a subchronic experiment

2021 ◽  
Vol 29 (5) ◽  
pp. 25-33
Author(s):  
Vadzim Michailovich Vasilkevich ◽  
Ruslan Valerievich Bogdanov ◽  
Ksenia Sergeevna Gilevskaya ◽  
Victoria Igorevna Kulikouskaya
Keyword(s):  
Biological Effects ◽  
Experimental Studies ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Pectin Content ◽  
Target Organs ◽  
Toxicological Studies ◽  
Threshold Doses ◽  
20 Nm ◽  
Dose Dependent

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields. Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20-30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed. Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase. Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.

Crohn Disease in Childhood and Adolescence

2018 ◽  
Author(s):  
Lori Zimmerman
Keyword(s):  
Weight Loss ◽  
Gastrointestinal Tract ◽  
Crohn Disease ◽  
Signs And Symptoms ◽  
Mucosal Healing ◽  
Joint Disease ◽  
Perianal Disease ◽  
Childhood And Adolescence ◽  
Chronic Inflammatory Condition ◽  
And Behavior

Crohn disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract (the mouth to the anus). CD is classified by location within the gastrointestinal tract and behavior of the disease (inflammatory, penetrating, and/or stricturing). It can also affect the extraintestinal tissue and cause perianal disease. It occurs from a complex interplay of genetic predisposition, altered gut microbiota, immunologic dysregulation, and likely environmental triggers. Children with CD often present with signs and symptoms related to the inflammation within their gastrointestinal tract. Most children with CD will present with diarrhea and abdominal pain, whereas some will present with rectal bleeding, fevers, weight loss, perianal disease, or joint disease. There is no single test to confidently diagnose a patient with CD. Instead, clinicians rely on a combination of biomarkers in the serum and stool, imaging studies, and endoscopic evaluation to make the diagnosis. The general aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and ultimately target mucosal healing. This review contains 3 figures, 3 tables and 34 references. Key Words: biologics, child, chronic diarrhea, Crohn disease, hematochezia, inflammatory bowel disease, immunodeficiency, pediatric, weight loss

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