scholarly journals Toluene Can Disrupt Rat Ovarian Follicullogenesis and Steroidogenesis and Induce Both Autophagy and Apoptosis

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1153
Author(s):  
Abdulkarem Alrezaki ◽  
Nouf Aldawood ◽  
Lamjed Mansour ◽  
Mukhtar Ahmed ◽  
Alexander V. Sirotkin ◽  
...  
Keyword(s):  
Low Dose ◽  
Ovarian Function ◽  
Ovarian Cells ◽  
Cell Proliferation And Differentiation ◽  
Female Wistar Rats ◽  
Toluene Exposure ◽  
Ovarian Structure ◽  
Encoding Gene ◽  
High Doses

Toluene has been shown to be highly toxic to humans and animals and can cause damage to various tissues. However, studies reporting its effects on ovarian function are still limited. In this study, we investigated the in vivo effect of toluene using female Wistar rats. We found that toluene exposure decreased ovarian weight and affected ovarian structure by increasing the number of abnormally growing follicles. Moreover, it significantly increased progesterone and testosterone levels. We also showed that toluene exposure decreased GDF-9 protein and its encoding gene. In addition, it inhibited the expression of most of the genes involved in granulosa cell proliferation and differentiation, such as Insl3, ccnd2 and actb. The TUNEL assay showed that apoptosis occurred at the middle and high doses only (4000 and 8000 ppm, respectively), whereas no effect was observed at the low dose (2000 ppm). Interestingly, we showed that toluene exposure induced autophagy as LC3 protein and its encoding gene significantly increased for all doses of treatment. These results may suggest that the activation of autophagy at a low dose of exposure was to protect ovarian cells against death by inhibiting apoptosis, whereas its activation at high doses of exposure triggered apoptosis leading to cell death.

scholarly journals Toll-Like Receptor Signaling in Airborne Burkholderia thailandensis Infection

2009 ◽  
Vol 77 (12) ◽  
pp. 5612-5622 ◽  
Author(s):  
T. Eoin West ◽  
Thomas R. Hawn ◽  
Shawn J. Skerrett
Keyword(s):  
Low Dose ◽  
Inflammatory Responses ◽  
High Dose ◽  
Tlr Signaling ◽  
Necrosis Factor Alpha ◽  
Airborne Infection ◽  
Essential Components ◽  
High Doses

ABSTRACT Melioidosis is a tropical disease endemic in southeast Asia and northern Australia caused by the gram-negative soil saprophyte Burkholderia pseudomallei. Although infection is often systemic, the lung is frequently involved. B. thailandensis is a closely related organism that at high doses causes lethal pneumonia in mice. We examined the role of Toll-like receptors (TLRs), essential components of innate immunity, in vitro and in vivo during murine B. thailandensis pneumonia. TLR2, TLR4, and TLR5 mediate NF-κB activation by B. thailandensis in transfected HEK293 or CHO cells. In macrophages, TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are required for tumor necrosis factor alpha production induced by B. thailandensis. In low-dose airborne infection, TLR4 is needed for early, but not late, bacterial containment, and MyD88 is essential for control of infection and host survival. TLR2 and TLR5 are not necessary to contain low-dose infection. In high-dose airborne infection, TLR2 deficiency confers a slight survival advantage. Lung and systemic inflammatory responses are induced by low-dose inhaled B. thailandensis independently of individual TLRs or MyD88. These findings suggest that redundancy in TLR signaling or other MyD88-dependent pathways may be important in pneumonic B. thailandensis infection but that MyD88-independent mechanisms of inflammation are also activated. TLR signaling in B. thailandensis infection is substantially comparable to signaling induced by virulent B. pseudomallei. These studies provide additional insights into the host-pathogen interaction in pneumonic Burkholderia infection.

scholarly journals Dose-response effects of equine chorionic gonadotrophin (eCG) and human chorionic gonadotrophin (hCG) on early embryonic development and viable pregnancy rate in rats

Reproduction ◽  
2001 ◽  
pp. 283-287 ◽  
Author(s):  
CF Tain ◽  
HH Goh ◽  
SC Ng
Keyword(s):  
Embryonic Development ◽  
Pregnancy Rate ◽  
Dose Response ◽  
Early Embryo ◽  
Chorionic Gonadotrophin ◽  
Early Embryonic Development ◽  
Embryo Yield ◽  
Female Wistar Rats ◽  
High Doses

The present study examined the dose-response effects of eCG treatment alone and in combination with various doses of hCG on early embryonic development in vivo and viable pregnancy rate in rats. Mated female Wistar rats were treated with eCG alone (0, 10, 20 or 40 iu), or with 20 iu eCG in combination with various doses of hCG (10, 20, 40 or 80 iu) administered 48 h later. The animals were killed on days 2, 3, 4, 5 or 14 of pregnancy and the numbers of embryos and fetuses recovered were scored. All rats treated with 0 or 10 iu eCG were pregnant. The pregnancy rate was reduced from 62.5% on day 2 to 25% on day 14 and from 31% on day 2 to 10% on day 14 in the groups treated with 20 and 40 iu eCG, respectively. The reduction in pregnancy rate induced by 20 iu eCG was negated by the increasing doses of hCG used. A 100% pregnancy rate was noted on days 2 and 3 in the groups treated with doses of hCG between 10 and 80 iu and from day 2 to day 4 in the groups treated with doses of hCG between 20 and 80 iu. However, a higher viable pregnancy rate was observed only in the group treated with 10 iu hCG compared with the group treated with 20 iu eCG and 0 iu hCG. These results imply that hyperstimulation of rats with high doses of eCG compromises pregnancy rate and markedly reduces litter size and that the addition of hCG is required for complete ovulation, which results in higher embryo yield and a delay in early embryo demise.

scholarly journals Chronic Exposure to High Doses of Bisphenol A Exhibits Significant Atrial Proarrhythmic Effects in Healthy Adult Rats

2021 ◽  
Vol 31 (3) ◽  
pp. 587-595
Author(s):  
Vasile Bogdan HALATIU ◽  
◽  
Alkora Ioana BALAN ◽  
Dan Alexandru COZAC ◽  
Remus BOBARNAC ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Chronic Exposure ◽  
Atrial Pacing ◽  
Autonomic Tone ◽  
Adult Rats ◽  
Female Wistar Rats ◽  
High Doses ◽  
Premature Beats

Objectives: We aimed to evaluate the effects of chronic exposure to bisphenol A (BPA) on atrial fibrillation (AF) occurrence in rats. Methods: Twenty-two healthy female Wistar rats were randomized into three groups: Control (no BPA; n=7), BPA (exposed to usual BPA doses; 50 μg/kg/day, 9 weeks; n=7), and hBPA (exposed to high BPA doses; 25 mg/kg/day, 9 weeks; n=8). 24-h ECG monitoring was performed using radiotelemetry ECG devices prior to and after transesophageal atrial pacing. Spontaneous and pacing-induced atrial arrhythmias, autonomic tone, and in vivo an in vitro atrial arrhythmogenicity-related parameters were evaluated. Results: All studied parameters were similar between Control and BPA (all p>0.05). However, compared to Control, hBPA presented more atrial premature beats both at baseline (p=0.04) and after pacing (p=0.03), more AF episodes (p<0.001) and of longer duration (p=0.02) following transesophageal stimulation, and significantly higher vagal tone (all p<0.05). Conclusions: Chronic exposure to high, but not usual BPA doses induced significant atrial proarrhythmic effects in healthy rats, and this may be at least partially due to BPA-induced vagal hyperactivation. Exposure to high BPA doses, such as that occurring in plastics industry workers, could favor AF occurrence even in the absence of underlying cardiovascular disease.

scholarly journals Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chunyu Huang ◽  
Zeming Liu ◽  
Mingzhu Chen ◽  
Liang Du ◽  
Chunping Liu ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Low Dose ◽  
Immune Escape ◽  
Redox Homeostasis ◽  
Low Dose Radiotherapy ◽  
Tumor Tissues ◽  
High Doses ◽  
Intracellular Hydrogen Peroxide

AbstractHigh doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes. Graphical Abstract

scholarly journals Tumor-Derived Biomimetic Nanozyme With Immune Evasion Ability For Synergistically Enhanced Low Dose Radiotherapy

2021 ◽  
Author(s):  
Chunyu Huang ◽  
Zeming Liu ◽  
Mingzhu Chen ◽  
Liang Du ◽  
Yongfa Zheng ◽  
...  
Keyword(s):  
High Performance ◽  
Low Dose ◽  
Immune Escape ◽  
Redox Homeostasis ◽  
Low Dose Radiotherapy ◽  
Tumor Tissues ◽  
High Doses ◽  
Intracellular Hydrogen Peroxide

Abstract High doses of radiation can cause serious side effects and drug resistance, high-performance radiosensitizers are urgently needed. To overcome this issue, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for use in combination with low-dose RT. CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH) and peroxidase activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2Gy) can provide a substantial suppression of tumor proliferation. To summarize, this is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

scholarly journals Impact of Eimeria tenella Oocyst Dose on Parasite Replication, Lesion Score and Cytokine Transcription in the Caeca in Three Breeds of Commercial Layer Chickens

2021 ◽  
Vol 8 ◽  
Author(s):  
Francesca Soutter ◽  
Dirk Werling ◽  
Sungwon Kim ◽  
Iván Pastor-Fernández ◽  
Virginia Marugán-Hernández ◽  
...  
Keyword(s):  
Low Dose ◽  
Eimeria Tenella ◽  
Lesion Score ◽  
Layer Chicken ◽  
Parasite Replication ◽  
Layer Chickens ◽  
High Doses ◽  
The Impact ◽  
Cytokine Transcription

Eimeria species parasites infect the gastrointestinal tract of chickens, causing disease and impacting on production. The poultry industry relies on anticoccidial drugs and live vaccines to control Eimeria and there is a need for novel, scalable alternatives. Understanding the outcomes of experimental infection in commercial chickens is valuable for assessment of novel interventions. We examined the impact of different infectious doses of Eimeria tenella (one low dose, three high doses) in three commercial layer chicken lines, evaluating lesion score, parasite replication and cytokine response in the caeca. Groups of eight to ten chickens were housed together and infected with 250, 4,000, 8,000 or 12,000 sporulated oocysts at 21 days of age. Five days post-infection caeca were assessed for lesions and to quantify parasite replication by qPCR and cytokine transcription by RT-qPCR. Comparison of the three high doses revealed no significant variation between them in observed lesions or parasite replication with all being significantly higher than the low dose infection. Transcription of IFN-γ and IL-10 increased in all infected chickens relative to unchallenged controls, with no significant differences associated with dose magnitude (p &gt; 0.05). No significant differences were detected in lesion score, parasite replication or caecal cytokine expression between the three lines of chickens. We therefore propose 4,000 E. tenella oocysts is a sufficient dose to reliably induce lesions in commercial layer chickens, and that estimates of parasite replication can be derived by qPCR from these same birds. However, more accurate quantification of Eimeria replication requires a separate low dose challenge group. Optimisation of challenge dose in an appropriate chicken line is essential to maximize the value of in vivo efficacy studies. For coccidiosis, this approach can reduce the numbers of chickens required for statistically significant studies and reduce experimental severity.

scholarly journals Regulation of the transcription factor E2F1 mRNA in ovarian granulosa cells of cattle

2019 ◽  
Vol 98 (1) ◽  
Author(s):  
Breanne C Morrell ◽  
M Chiara Perego ◽  
Excel Rio S Maylem ◽  
Lingna Zhang ◽  
Luis F Schütz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Ovarian Function ◽  
Follicular Development ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Mrna Abundance ◽  
Concomitant Treatment ◽  
Ovarian Cells ◽  
Cell Proliferation And Differentiation

Abstract The E2F family of transcription factors plays an important role in the control of the cell cycle, cell proliferation, and differentiation, and their role in ovarian function is just emerging. Although some evidence suggests a possible role of E2F1 in ovarian follicular development, what regulates its production in ovarian cells is unknown. Objectives of this study were to determine whether: (i) E2F1 gene expression in granulosa cells (GCs) and theca cells (TCs) change with follicular development and (ii) E2F1 mRNA abundance in TC and GC is hormonally regulated. Using real-time PCR, E2F1 mRNA abundance in GC was 5.5-fold greater (P &lt; 0.05) in small (SM; 1 to 5 mm) than large (LG; &gt;8 mm) follicles, but in TC, E2F1 expression did not differ among follicle sizes. SM-follicle GC had 2.1-fold greater (P &lt; 0.05) E2F1 mRNA than TC. In SM-follicle GC, FGF9 induced a 7.6-fold increase in E2F1 mRNA abundance; however, FGF9 did not affect (P &gt; 0.10) abundance of E2F1 mRNA in LG-follicle TC or GC. Follicle-stimulating hormone (FSH) had no effect (P &gt; 0.10) on E2F1 gene expression in SM- or LG-follicle GC. SM-follicle GC were concomitantly treated with insulin-like growth factor 1 (30 ng/mL), FSH (30 ng/mL), and either 0 or 30 ng/mL of FGF9 with or without 50 µM of an E2F inhibitor (E2Fi; HLM0064741); FGF9 alone increased (P &lt; 0.05) GC numbers, whereas E2Fi alone decreased (P &lt; 0.05) GC numbers, and concomitant treatment of E2Fi with FGF9 blocked (P &lt; 0.05) this stimulatory effect of FGF9. Estradiol production was inhibited (P &lt; 0.05) by FGF9 alone and concomitant treatment of E2Fi with FGF9 attenuated (P &lt; 0.05) this inhibitory effect of FGF9. SM-follicle GC treated with E2Fi decreased (P &lt; 0.05) E2F1 mRNA abundance by 70%. Collectively, our studies show that GC E2F1 mRNA is developmentally and hormonally regulated in cattle. Inhibition of E2F1 reduced FGF9-induced GC proliferation and attenuated FGF9-inhibited estradiol production, indicating that E2F1 may be involved in follicular development in cattle.

scholarly journals The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep

Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 721-732 ◽  
Author(s):  
B K Campbell ◽  
N R Kendall ◽  
V Onions ◽  
R J Scaramuzzi
Keyword(s):  
Low Dose ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Insulin Response ◽  
Acute Effect ◽  
Arterial Infusion ◽  
Fourfold Increase ◽  
Glucose Challenge ◽  
Insulin Responses

Glucose is a critical metabolic fuel in most mammals although many foodstuffs also contain high levels of the monosaccharides, galactose and fructose. The aims of this work were to determine the insulin response to challenges of these sugars (experiment 1) and to examine the effect of systemic (experiment 2) and direct ovarian (experiment 3) infusion of these monosaccharides on ovarian function in ewes with autotransplanted ovaries. In experiment 1, both fructose (fourfold increase peaking in 2 h) and galactose (twofold increase; 30 min) elicited markedly different (P<0.001) insulin responses than glucose (sevenfold increase; 20 min) although the total amount released following fructose and glucose challenge was similar. In experiment 2, low-dose systemic fructose infusion had no acute effect on insulin but did depress FSH (P<0.05), and following the end of fructose infusion, a transient increase in FSH and insulin was observed (P<0.05), which was associated with an increase (P<0.05) in ovarian oestradiol and androstenedione secretion. Systemic infusion of neither glucose nor galactose had a significant effect on ovarian steroidogenesis although glucose acutely suppressed insulin levels. In contrast, ovarian arterial infusion of fructose and glucose had no effect on ovarian function whereas galactose suppressed ovarian follicle number and steroid secretion (P<0.05). In conclusion, this work indicates that fructose and galactose can influence ovarian functionin vivoin sheep and that different mechanisms are involved. Thus, fructose exerts stimulatory effects through indirect modulation of peripheral insulin and/or gonadotrophin levels whereas galactose exerts primarily suppressive effects by direct actions on the ovary.

Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport

1982 ◽  
Vol 243 (6) ◽  
pp. G455-G462 ◽  
Author(s):  
G. M. Groothuis ◽  
M. J. Hardonk ◽  
K. P. Keulemans ◽  
P. Nieuwenhuis ◽  
D. K. Meijer
Keyword(s):  
Biliary Excretion ◽  
Low Dose ◽  
Blood Stream ◽  
Water Soluble ◽  
Salt Transport ◽  
High Doses ◽  
Pentobarbital Sodium Anesthesia ◽  
Taurocholate Transport ◽  
Bile Salt Transport

A combination of autoradiography of water-soluble compounds and normal and retrograde perfusions was used to study whether there was a heterogeneity in bile salt transport between zone 1 and zone 3 hepatocytes of the rat and, if so, whether such a heterogeneity was due to the localization of these cells in the liver blood-stream, to intrinsic cellular differences, or to both. When a low dose of [3H]taurocholate was administered under pentobarbital sodium anesthesia in vivo or to normally perfused livers, the label was localized primarily in zone 1; in livers perfused in a retrograde direction, it appeared predominantly in zone 3. High doses of [3H]taurocholate administered in vivo and in normal and retrograde perfusions resulted in a more homogeneous labeling of the acini. The plasma disappearance of [3H]taurocholate was similar in normal and retrograde perfusions, but in the latter biliary excretion occurred at a considerably slower rate. From these results it is concluded that at low doses bile salts are primarily transported by zone 1 cells. Zone 3 cells appear to be able to take up taurocholate with ease, but their biliary excretion is slower compared with zone 1 cells.

scholarly journals Requirements for Identification of Low Dose and Non-Linear Mutagenic Responses to Ionising Radiation

Dose-Response ◽  
2007 ◽  
Vol 5 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
Pamela J. Sykes ◽  
Tanya K. Day
Keyword(s):  
Low Dose ◽  
Threshold Model ◽  
Dose Range ◽  
Cellular Transformation ◽  
Low Dose Radiation ◽  
Spontaneous Frequency ◽  
High Doses ◽  
Dose Radiation

Cancer results from multiple changes in gene expression that can occur both genetically and epigenetically. High doses of radiation can lead to mutations and cancer. At high doses the number of mutations caused by radiation is essentially linear with dose. Low dose radiation induced protective responses observed for cancer in vivo and cellular transformation in vitro would predict that hormetic responses would also be observed in mutation assays. Although there are a large number of different mutation assays available, very few are able to detect changes in mutation frequency in response to very low doses of DNA damaging agents. The easiest way to cope with this lack of data in the low dose range is to invoke a linear-no-threshold model for risk assessment. The reasons for the lack of data are discussed. In order to identify hormetic mutation responses, assays need to have a spontaneous frequency that is high enough to enable a reduction below spontaneous frequency to be detected in a feasible number of scored cells and also need to be able to identify both genetic and epigenetic changes. The pKZ1 chromosomal inversion assay fits the criteria for detecting hormetic responses to low dose radiation.

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