scholarly journals Shotgun metagenomics and metabolomics reveal glyphosate alters the gut microbiome of Sprague-Dawley rats by inhibiting the shikimate pathway

2019 ◽  
Author(s):  
Robin Mesnage ◽  
Maxime Teixeira ◽  
Daniele Mandrioli ◽  
Laura Falcioni ◽  
Quinten Raymond Ducarmon ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Shikimic Acid ◽  
Biological Effects ◽  
Shikimate Pathway ◽  
Control Group ◽  
Human Populations ◽  
Sprague Dawley ◽  
Epsp Synthase ◽  
Shotgun Metagenomics ◽  
Rat Gut

AbstractThere is intense debate as to whether glyphosate can interfere with aromatic amino acid biosynthesis in microorganisms inhabiting the gastrointestinal tract, which could potentially lead to negative health outcomes. We have addressed this major gap in glyphosate toxicology by using a multi-omics strategy combining shotgun metagenomics and metabolomics. We tested whether glyphosate (0.5, 50, 175 mg/kg bw/day), or its representative EU commercial herbicide formulation MON 52276 at the same glyphosate equivalent doses, has an effect on the rat gut microbiome in a 90-day subchronic toxicity test. Clinical biochemistry measurements in blood and histopathological evaluations showed that MON 52276 but not glyphosate was associated with statistically significant increase in hepatic steatosis and necrosis. Similar lesions were also present in the liver of glyphosate-treated groups but not in the control group. Caecum metabolomics revealed that glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase in the shikimate pathway as evidenced by an accumulation of shikimic acid and 3-dehydroshikimic acid. Levels of caecal microbiome dipeptides involved in the regulation of redox balance (γ-glutamylglutamine, cysteinylglycine, valylglycine) had their levels significantly increased. Shotgun metagenomics showed that glyphosate affected caecum microbial community structure and increased levels of Eggerthella spp. and Homeothermacea spp.. MON 52276, but not glyphosate, increased the relative abundance of Shinella zoogleoides. Since Shinella spp. are known to degrade alkaloids, its increased abundance may explain the decrease in solanidine levels measured with MON 52776 but not glyphosate. Other glyphosate formulations may have different effects since Roundup® GT Plus inhibited bacterial growth in vitro at concentrations at which MON 52276 did not present any visible effect. Our study highlights the power of a multiomics approach to investigate effects of pesticides on the gut microbiome. This revealed the first biomarker of glyphosate effects on rat gut microbiome. Although more studies will be needed to ascertain if there are health implications arising from glyphosate inhibition of the shikimate pathway in the gut microbiome, our findings can be used in environmental epidemiological studies to understand if glyphosate can have biological effects in human populations.Graphical Abstract

scholarly journals Gut microbiome signature of Viliuisk encephalomyelitis in Yakuts includes an increase in microbes linked to lean body mass and eating behaviour

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Veronika Kuznetsova ◽  
Alexander Tyakht ◽  
Lyudmila Akhmadishina ◽  
Vera Odintsova ◽  
Natalia Klimenko ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Body Mass ◽  
Gut Microbiome ◽  
Dietary Habits ◽  
Eating Behaviour ◽  
Cortical Atrophy ◽  
Control Group ◽  
Human Populations ◽  
Endemic Diseases ◽  
The Impact

Abstract Background Viliuisk encephalomyelitis (VE) is a rare endemic neurodegenerative disease occurring in the Yakut population of Northeastern Siberia. The main clinical features of VE are spasticity, dysarthria, dementia, central paresis and paralysis, and cortical atrophy observed via MRI. Many hypotheses have been proposed regarding its etiology, including infectious agents, genetics, environmental factors, and immunopathology. Each of these hypotheses has been supported to some extent by epidemiological and experimental data. Nevertheless, none of them has been decisively proven. Gut microbiome is one of the factors that might be involved in VE pathogenesis. Results Here we performed a pilot survey of the stool microbiomes of Yakut subjects with VE (n = 6) and without VE (n = 11). 16S rRNA sequencing showed that in comparison with the control group, the Yakuts with VE had increased proportions of Methanobrevibacter and Christensenella, which are reported to be linked to body mass index, metabolism, dietary habits and potentially to neurodegenerative disorders. The identified associations suggest that the microbiome may be involved in VE. Overall, the Yakut microbiome was quite specific in comparison with other populations, such as metropolitan Russians and native inhabitants of the Canadian Arctic. Conclusions Describing the gut microbiome of indigenous human populations will help to elucidate the impact of dietary and environmental factors on microbial community structure and identify risks linked to the lifestyles of such groups as well as endemic diseases.

scholarly journals Elevated Levels of Apelin-36 in Heart Failure Due to Chronic Systemic Hypoxia

2018 ◽  
Vol 28 (03) ◽  
pp. 194-199
Author(s):  
Frans Ferdinal ◽  
David Limanan ◽  
Retno Dwi Rini ◽  
Rio Alexsandro ◽  
Rizal Helmi
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Structural Damage ◽  
Molecular Mechanisms ◽  
Ventricular Remodeling ◽  
Biological Effects ◽  
Orphan Receptor ◽  
Control Group ◽  
Sprague Dawley ◽  
Systemic Hypoxia

AbstractApelin is a novel adipokine identified as an endogenous ligand of the specific orphan receptor APJ. Among the various isoforms of apelin, an increase in the apelin-36 plasma level has been associated with oxidative stress, and this isoform has various biological effects, such as positive inotropic, vasodilatory, and antiatherosclerotic effects. Therefore, apelin-36 may be used as a biomarker of heart failure (HF). Advances in the understanding of the molecular mechanisms underlying HF cannot be achieved without the use of animal models. However, it is unclear whether chronic systemic hypoxia can cause HF in rats. The present study aimed to determine whether chronic systemic hypoxia can cause HF in rats and whether apelin-36 can be used as a biomarker of HF. The study included Sprague–Dawley rats. The rats were randomly divided into seven groups (n = 4). One of the groups was a control group, and the six other groups were exposed to hypoxia (8% O2) for different durations (6 hours, 1 day, 3 days, 5 days, 7 days, and 14 days). The exposure groups showed ventricular hypertrophy accompanied by myocardial structural damage, which indicated ventricular remodeling. In addition, the exposure groups showed elevated apelin-36 plasma levels and signs of oxidative stress. Moreover, gel electrophoresis of heart tissue showed five bands that corresponded to apelin isotypes, including apelin-36. In an experimental rat HF model with chronic systemic hypoxia, apelin-36 was elevated along with oxidative stress. Apelin-36 along with oxidative stress may serve as a biomarker of HF in this model.

scholarly journals Association of zinc administration with growth suppression of intracranial aneurysms via induction of A20

2020 ◽  
pp. 1-7 ◽  
Author(s):  
Kosuke Hayashi ◽  
Hiroharu Kataoka ◽  
Manabu Minami ◽  
Taichi Ikedo ◽  
Takeshi Miyata ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Biological Effects ◽  
Nuclear Factor Κb ◽  
Male Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Zinc Treatment ◽  
Sulfate Heptahydrate ◽  
Treatment Groups ◽  
Surgically Induced

OBJECTIVEZinc is an essential micronutrient with multiple biological effects, including antiinflammation. Previously, the authors demonstrated that the pathogenesis of intracranial aneurysms (IAs) is strongly related to chronic inflammation. In this study, the authors investigated whether administration of zinc inhibits the growth of IAs in a rat model.METHODSThe authors analyzed surgically induced IAs in Sprague-Dawley male rats, which were subsequently treated with intraperitoneal injections of zinc sulfate heptahydrate (ZnSO4; 3 mg/kg/day) or vehicle for 4 weeks.RESULTSSize and wall thickness ratios of experimentally induced IAs were assessed in both treatment groups after induction and in a control group. The effects of zinc administration in IAs were examined by immunohistochemistry and Western blotting. Zinc administration significantly suppressed aneurysm size and also preserved the internal elastic lumen. Administration of zinc significantly attenuated infiltration of macrophages into IAs.CONCLUSIONSZinc treatment significantly increased expression of the antiinflammatory signaling protein A20, an inhibitor of the nuclear factor κB (NF-κB) pathway, in rat IAs. Zinc administration may prevent the growth of rat IAs by inducing A20-attributed inactivation of NF-κB signaling.

scholarly journals Role of essential oils in antioxidant capacity and immunity in a rat model of mixed stress

2021 ◽  
Vol 51 (4) ◽  
pp. 426-436
Author(s):  
N. Seyidoglu ◽  
E. Koseli ◽  
R. Gurbanli ◽  
C. Aydin
Keyword(s):  
Essential Oils ◽  
Water Consumption ◽  
Rat Model ◽  
Animal Feed ◽  
Biological Effects ◽  
Interleukin 4 ◽  
Control Group ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Stressed Group

Animal wellbeing is a balance between environmental stress and nutrition that regulates homeostasis. Augmentation of animal feed with essential oils can promote homeostasis. The present study was designed to observe the biochemical, immunological, and biological effects of daily administration of a mixture of essential oils (EOM) in a stressed rat model. Forty-eight adult male Sprague Dawley rats were  randomly allocated to four groups, namely a control group (C), a stressed group (S), a treated group (Tr), and a stressed group that  received the treatment (TrS). The treatment was applied by adding EOM to the water (0.2 ml/l) three days per week for 28 days. Two  chronic stressors (isolation and crowding) were applied to animals in groups S and TrS. Total oxidant status (TOS) increased in the S group  compared with C, whereas it decreased when fed with EOM. Although TOS was the same in S and C, it increased in Tr compared with C. There was a significant increase in interleukin 4 (IL-4) in S compared with C, and EOM reversed the IL-4 level. Nevertheless, an increase was seen in the weights of the liver, intestine, brain, and testes in TrS compared with S. The increase in water intake was a result of stress, but feeding with EOM decreased water consumption gradually. This study showed that 0.2 ml/l EOM had protective effects on antioxidant status, immunity and liver function, and decreased water consumption under stress conditions.

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

Effect of Green Tea and (-)-Epigallocatechin Gallate on the Pharmacokinetics of Rosuvastatin

2020 ◽  
Vol 21 (6) ◽  
pp. 471-478
Author(s):  
Shenjia Huang ◽  
Qingqing Xu ◽  
Linsheng Liu ◽  
Yicong Bian ◽  
Shichao Zhang ◽  
...  
Keyword(s):  
Green Tea ◽  
Cell Model ◽  
Hek293t Cell ◽  
Epigallocatechin Gallate ◽  
Drug Uptake ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Curve ◽  
Uptake And Transport

Background: Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin. Objective: This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism. Methods: Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). Results: GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050). Conclusion: GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.

Motor Recovery after Chronic Spinal Cord Transection in Rats: A Proof-of-Concept Study Evaluating a Combined Strategy

2019 ◽  
Vol 18 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Antonio Ibarra ◽  
Erika Mendieta-Arbesú ◽  
Paola Suarez-Meade ◽  
Elisa García-Vences ◽  
Susana Martiñón ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Strategies ◽  
Chronic Phase ◽  
Motor Recovery ◽  
Neural Regeneration ◽  
Histological Evaluation ◽  
Control Group ◽  
Proof Of Concept ◽  
Sprague Dawley ◽  
Concept Study

Background: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP). Methods: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers. Results: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers. Conclusion: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.

scholarly journals Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

2021 ◽  
Vol 18 (4) ◽  
pp. 1645
Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Endurance Exercise ◽  
Field Tests ◽  
Treadmill Running ◽  
Control Group ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies

2021 ◽  
pp. 002367722110018
Author(s):  
Yuri K Sinzato ◽  
Eduardo Klöppel ◽  
Carolina A Miranda ◽  
Verônyca G Paula ◽  
Larissa F Alves ◽  
...  
Keyword(s):  
Adult Life ◽  
Tolerance Test ◽  
Full Term ◽  
Female Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Oral Glucose ◽  
Postnatal Life ◽  
Sprague Dawley ◽  
Term Pregnancy

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague–Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.

scholarly journals The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  
Keyword(s):  
Sperm Count ◽  
Semen Analysis ◽  
Study Groups ◽  
Testicular Biopsy ◽  
Male Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Sprague Dawley ◽  
Left Testis ◽  
Significant Difference

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.

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