ACTIONS OF CATECHOL OESTROGENS ON CONCENTRATIONS OF SERUM LUTEINIZING HORMONE IN THE ADULT CASTRATED RAT: VARIOUS EFFECTS OF 4-HYDROXYOESTRADIOL AND 2-HYDROXYOESTRADIOL

1981 ◽  
Vol 89 (2) ◽  
pp. 289-295 ◽  
Author(s):  
S. FRANKS ◽  
N. J. MacLUSKY ◽  
S. J. NAISH ◽  
F. NAFTOLIN
Keyword(s):  
Serum Levels ◽  
Male Rats ◽  
Hydroxyl Group ◽  
High Dose ◽  
Binding Properties ◽  
Potent Effect ◽  
Naturally Occurring ◽  
Serum Luteinizing Hormone ◽  
The Right

The pharmacological effect of 2-hydroxyoestradiol (2-OHE2) and 4-OHE2 on concentrations of LH in the chronically castrated rat have been compared with that of oestradiol in order to determine whether the in-vivo activity is altered by insertion of a hydroxyl group at position 2 or 4 of the aromatic A ring; these derivatives are naturally occurring oestrogen metabolites. Four groups of six adult male rats were used 4 weeks after bilateral orchidectomy. The right jugular vein was exposed under ether anaesthesia and a basal blood sample taken (10.00 h) immediately before an intravenous injection of vehicle alone (0·1 ml ethanol with 0·01 % ascorbic acid), oestradiol, 2-OHE2 or 4-OHE2 (10 μg of each in 0·1 ml vehicle). Blood was taken from each animal at 2, 4, 6, 8 and 24 h after treatment and serum assayed for LH. Baseline LH levels were similar in the four groups. At 2 h there was no change in 2-OHE2-treated rats but there was a significant decrease of serum levels of LH in rats treated with oestradiol and 4-OHE2 compared with vehicle-treated controls. The decrease in LH was quantitatively similar in oestradiol- and 4-OHE2-treated groups and was sustained at 4, 6 and 8 h, returning to control values at 24 h. In subsequent experiments the effects of lower doses of these two steroids were compared and the potency of 4-OHE2 was estimated to be about 25% that of oestradiol. In a further experiment, 2-OHE2 (100 μg) had no effect when given alone, but when injected i.v. immediately before treatment with 1 μg oestradiol, it was able to inhibit the suppression of LH by oestradiol. In conclusion, 4-OHE2 had a potent effect in lowering plasma LH levels whereas 2-OHE2, even at a high dose (100 μg), did not suppress LH but it was able to inhibit the effect of oestradiol. These differences in biological activity may reflect more rapid metabolism of 2-OHE2 or differences in binding properties of these catechol oestrogens to the oestrogen receptor.

scholarly journals In vivo uptake of [14C]leucine by skeletal muscle ribosomes after injury in rats fed two levels of protein

1969 ◽  
Vol 23 (2) ◽  
pp. 271-280 ◽  
Author(s):  
V. R. Young ◽  
P. C. Huang
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Male Rats ◽  
Thigh Muscle ◽  
Left Femur ◽  
The Right ◽  
And Control ◽  
The Relationship ◽  
In Vivo Uptake

1. After 14 days on a diet containing 5 or 25% casein male rats received a fracture of the left femur. Four hours before they were killed the injured and control rats were injected with [1-14C]leucine; the incorporation of radioactivity into an isolated fraction of skeletal muscle ribosomes was studied 6, 12, 24, 48, 72, 96 and 228 h after injury.2. The incorporation of [14C]leucine into the ribosome fraction in right thigh muscles dropped to 40% of control values 72 h after fracture in well-nourished rats and after 96 h with diets containing 5 or 25%, casein.3. The specific activity of the trichloroacetic acid-soluble fraction of muscle from injured rats was equal to or higher than that of the controls during the first 72 h but lower at 96 h.4. These results suggest that a reduced incorporation of amino acids by ribosomes from the right thigh muscle occurred on day 3 after fracture in the group receiving 25% casein but not in the group receiving 5% casein.5. Muscle RNA and DNA concentrations were not affected by the injury.6. The relationship between these findings and the loss of muscle N after injury is discussed.

scholarly journals Intratracheal administration of bone marrow c-kit+ cells offered hopes in ameliorating asthmatic pathologies via the control of miRNA-133 and -126

2020 ◽  
Author(s):  
Reza Rahbarghazi ◽  
Rana Keyhanmanesh ◽  
Fatemeh Mirershadi ◽  
Hossain Heiran ◽  
Hesam Saghaei Bagheri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Serum Levels ◽  
Male Rats ◽  
Pathological Examination ◽  
Pcr Analysis ◽  
Control Group ◽  
Intratracheal Administration ◽  
Therapeutic Outcomes ◽  
Mirnas Expression

Abstract Background There are still challenges regarding c-kit+ cells therapeutic outcome in the clinical setting. Here, we examined of c-kit+ cells effect on the alleviation of asthma by modulating miRNAs expression.MethodsTo induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (each in 6 rats). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) were assessed by real-time PCR analysis.ResultsPathological examination, Th1 and Th2 associated cytokines fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared to the control group (p<0.05). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had potential to changes INF-γ/IL-4 ratio and closed to the normal values compared to matched-control asthmatic rats (p<0.05). We also found that c-kit+ cells regulated the expression of miRNA-126 and -133, indicated by increase of miRNA-133 and decrease of miRNA-126 compared to cell-free sensitized groups (p<0.05). c-kit- cells were unable to promote any therapeutic outcomes in asthmatic milieu.ConclusionsIn overall, c-kit+ cells had potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.

scholarly journals Protective effect of Curcumin against rotenone-induced Substantia nigra pars compacta neuronal dysfunction

2021 ◽  
Author(s):  
Lilit Vahan Darbinyan ◽  
Lilia Eduard Hambardzumyan ◽  
Larisa Paylak Manukyan ◽  
Karen Vazgen Simonyan ◽  
Carlos Augusto Carvalho de Vasconcelos ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Therapeutic Agent ◽  
Male Rats ◽  
Substantia Nigra Pars Compacta ◽  
Nissl Staining ◽  
Histological Changes ◽  
Naturally Occurring ◽  
The Brain

Abstract Rotenone is involved in the degeneration of dopaminergic neurons, and curcumin may prevent or effectively slow the progression of Parkinson disease (PD). Previous research has shown that the naturally occurring phenolic compound curcumin can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative diseases. The present study involves investigation of rotenone induced histological changes in the brain areas, hippocampus using Nissl staining after 35 day of subcutaneous injection administration of rotenone in adult male rats. In this study, we investigated whether curcumin protects against rotenone-induced dopaminergic neurotoxicity in a rat model by in vivo electrical recording from Substantia nigra pars compacta (SNc). Curcumin treatment significantly improved electrical activity of neurons in the SNc of rotenone-induced PD model rats. The pattern of histological alterations corresponds with electrophysiological manifestations.

312 An Evaluation of the Clinical and Histological Effects of High Dose Radiosurgery on the Rat Dorsal Root Ganglion

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 266-267
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Erin Paschel ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
The Body ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Histopathological Response ◽  
Histological Techniques ◽  
Sensory Deficits ◽  
The Right

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a safe and effective technique to create lesions of the brain and trigeminal nerve (TGN) in order to achieve neuromodulation. The lumbar dorsal root ganglion (DRG) contains the body of the sensory neurons responsible for pain sensitivity and can be targeted to treat chronic and debilitating pain in the extremities. Neuromodulation of the DRG might therefore improve chronic peripheral pain. This study was performed to determine the feasibility as well as clinical and histological effects of delivering high dose SRS targeted to the lumbar DRG in a rat model. METHODS Four Sprague Dawley male rats underwent 80 Gy maximum dose single-fraction SRS to the left L5 and L6 DRG using the Leksell Gamma Knife Icon (Elekta, Atlanta, GA) with onboard cone-beam CT imaging using 4 mm diameter collimators. The right L5 and L6 DRGs served as the controls. The animals were evaluated for motor and sensory deficits every two weeks. Two animals were sacrificed at 3 and two at 6 months after SRS. The lumbar spines were harvested and decalcified. Common histological techniques (Masson trichrome, Prussian blue) were used to assess for fibrosis and demyelination. RESULTS >No detectable motor or sensory deficits were seen in any animal. Histological changes including fibrosis and loss of myelin were noted to the left L5 and L6 DRGs, but not the right side control DRGs. Fibrotic changes within the vertebral body were also evident on the treated sides of the vertebral bodies. CONCLUSION We were able to detect a demyelinating histopathological response from SRS delivered to the DRG in rats. Since such changes mimic those seen after trigeminal SRS in experimental animals, we hypothesize that radiosurgery may be a potential option in chronic spinal radicular pain amenable to neuromodulation.

scholarly journals Inhibition of cyclo-oxigenase-2 activity does not abolish the anabolic effect of prostaglandin E2 in vivo or in vitro

2002 ◽  
Vol 174 (1) ◽  
pp. 127-135 ◽  
Author(s):  
M Weinreb ◽  
A Kelner ◽  
S Keila
Keyword(s):  
Bone Formation ◽  
Bone Tissue ◽  
Receptor Expression ◽  
Male Rats ◽  
Nodule Formation ◽  
High Dose ◽  
Anabolic Effect ◽  
Cox 2

It was previously reported that the expression of cyclo-oxigenase-2 (COX-2) is induced by prostaglandin E(2) (PGE(2)) in vitro in an osteogenic cell line and organ culture, suggesting an autoamplification mechanism. In this study, we first tested whether this phenomenon also occurs in bone tissue in vivo and found that a single anabolic dose of PGE(2) (5 mg/kg) induced (between 30 and 120 min) in rat tibiae, an increase in the mRNA level of COX-2 (2.5- to 9-fold) but not that of COX-1. Secondly, to test whether COX-2 activity in generating endogenous prostaglandins (PGs) is required for the in vivo anabolic properties of PGE(2), young male rats were injected daily with either vehicle (8% ethanol) or 5 mg/kg PGE(2) for 21 days. PGE(2)-injected rats received, 45 min prior to PGE(2), either dimethyl sulphoxide (as vehicle) or one of two doses of NS-398, a selective COX-2 inhibitor: a low dose (3 mg/kg) or a high dose (10 mg/kg). PGE(2) increased bone formation (measured as cancellous mineralizing surface, mineral apposition rate and bone formation rate) and bone mass (measured as cancellous bone area and surface and cortical width). None of these increases was suppressed by pre-administration of NS-398. In contrast, the high dose of NS-398 effectively suppressed an increase in rat hind-paw volume induced by a local carrageenan injection. Furthermore, since COX-2 inactivation may affect PG receptor expression, we found that pre-administration of NS-398 did not abolish the induction in EP(4) receptor mRNA levels, caused by PGE(2) in rat bone tissue. For in vitro testing, rat femoral bone marrow stromal cell cultures were initiated and were incubated in the absence or presence of PGE(2) at 100 nM (as an inducer) and with increasing concentrations of NS-398 (10(-8) M to 10(-5) M) for 21 days, after which time mineralized (Von-Kossa positive) nodules were counted. PGE(2) increased nodule formation as previously reported; however, NS-398 reduced nodule formation in both control and PGE(2)-treated cultures to the same extent. We conclude that while the level of COX-2 mRNA is increased in vivo by administration of PGE(2), inhibition of its activity (i.e. generation of endogenous PGs) does not abolish the anabolic effect of PGE(2).

scholarly journals Increased In Vivo Antibody Activity Against Interferon α, Interleukin-1α, and Interleukin-6 After High-Dose Ig Therapy

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2376-2380 ◽  
Author(s):  
Christian Ross ◽  
Morten Svenson ◽  
Henrik Nielsen ◽  
Charlotte Lundsgaard ◽  
Morten Bagge Hansen ◽  
...  
Keyword(s):  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interferon Α ◽  
High Dose ◽  
Antibody Activity ◽  
High Avidity ◽  
Cytokine Levels ◽  
Antiviral Activities ◽  
Interleukin 1Α

Abstract High-avidity antibodies against interferon α (IFNα), interleukin-1α (IL-1α), and IL-6 have been demonstrated in preparations of normal human IgG, and in vivo modulation of these cytokines may therefore account for immunomodulatory and anti-inflammatory effects of high-dose intravenous IgG therapy. We have investigated the in vivo recovery and the effect on serum cytokine levels of antibodies to IFNα, IL-1α, and IL-6 infused with IgG preparations. Fifteen treatment series of 0.4 g IgG/kg/d were administered over 3 days to eight patients with autoimmune diseases. All IgG preparations contained variable amounts of antibodies binding to 125I-labeled human IFNα2A, -IL-1α, and -IL-6, and the contents of these molecules correlated with increased levels in serum anticytokine activities after IgG infusion. The infused anti–IL-1α antibody activity was fully recovered, whereas the recovery of anti-IFNα2A antibodies was significantly reduced. Serum antiviral activities were significantly reduced after IgG therapy (before, 0 to 5.6 IU/mL; after, 0 to 0.6 IU/mL). In contrast, enzyme-linked immunosorbent assay (ELISA) showed no significant reduction in the serum levels of IL-6 (before, 1 to 70 pg/mL; after, 2 to 55 pg/mL), and the levels of IL-1α were consistently below the detection limit (<30 pg/mL). In conclusion, increased levels of antibodies to IFNα2A, IL-1α, and IL-6 occurred in patients receiving IgG and this reduced the serum antiviral activity.

Significance of experimental studies for assessing adverse effects of endocrine-disrupting chemicals

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2125-2141 ◽  
Author(s):  
L. E. Gray ◽  
P. M. D. Foster
Keyword(s):  
Adverse Effects ◽  
Statistical Power ◽  
Experimental Studies ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Tier 2 ◽  
In Vivo Assays ◽  
Endocrine Disrupting

The U.S. Environmental Protection Agency (USEPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce androgen (AR) and estrogen (ER) receptor-mediated effects in mammals and other animals. The utility of this approach is based upon the knowledge that mechanisms of endocrine-disrupting chemical (EDC) action are highly conserved at the cellular and molecular levels among vertebrates. Some EDC mechanisms also are shared with invertebrates. High-priority chemicals would be evaluated in a Tier 1 screening (T1S) battery, and chemicals that are positive in T1S would then be tested in Tier 2 (T2). T1S includes in vitro ER and AR receptor binding and/or gene expression, an assessment of steroidogenesis and mammalian (rat) and nonmammalian (fish) in vivo assays. In vivo, the uterotropic assay detects estrogens and antiestrogens, while steroidogenesis, antithyroid activity, antiestrogenicity, and HPG function are assessed in a pubertal female assay. Antiandrogens are detected in the Hershberger assay (weight of androgen-dependent tissues in castrate-immature-male rats). Fish and amphibian assays are also being developed to identify EDCs. Several alternative mammalian in vivo assays have been proposed. Of these, a short-term pubertal male rat assay appears most promising. T1S is designed to be sensitive to EAT activities, but many of the effects detected at the screening level would not be considered adverse, the dosage levels may be high, and the route of administration used may not be the most relevant. However, issues of adversity, dose response, and route(s) of exposure would be resolved in the testing phase. In addition to using an enhanced multigenerational test for Tier 2, an in utero-lactational screening protocol is also being evaluated by USEPA for use in T2 or T1S. For T2, the numbers of endocrine-sensitive end-points and offspring (F1) examined in multigenerational tests need to be expanded for EDCs in a thoughtful manner, based in part upon the results of T1S. In addition, for some chemicals histological examination of 10 adult F1 per sex in only the control and high-dose groups provides inadequate statistical power to detect low-dose lesions induced during development. In these cases, we propose that all the offspring be examined after puberty for gross and histological reproductive abnormalities. Since EDCs, like the phthalates and AR-antagonists, produce characteristic profiles, or syndromes, of adverse effects, data need to be reported in a manner that clearly identifies the proportion of animals displaying one or more of the abnormalities in a syndrome. Consideration should be given to tailoring T2, based on the results of T1S to assure that all of the effects in such chemically induced developmental syndromes are included in the study.

scholarly journals Effects of Diethyl Phosphate, a Non-Specific Metabolite of Organophosphorus Pesticides, on Serum Lipid, Hormones, Inflammation, and Gut Microbiota

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 2003 ◽  
Author(s):  
Fangwei Yang ◽  
Jinwang Li ◽  
Guofang Pang ◽  
Fazheng Ren ◽  
Bing Fang
Keyword(s):  
Gut Microbiota ◽  
Organophosphorus Pesticides ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Epidemiological Studies ◽  
Sensu Stricto ◽  
Male Rats ◽  
High Dose ◽  
Diethyl Phosphate

Organophosphorus pesticides (OPs) can be metabolized to diethyl phosphate (DEP) in the gut environment, which may affect the immune and endocrine systems and the microbiota. Correlations between OPs and diseases have been established by epidemiological studies, mainly based on the contents of their metabolites, including DEP, in the serum or urine. However, the effects of DEP require further study. Therefore, in this study, adult male rats were exposed to 0.08 or 0.13 mg/kg DEP for 20 weeks. Serum levels of hormones, lipids, and inflammatory cytokines as well as gut microbiota were measured. DEP significantly enriched opportunistic pathogens, including Paraprevotella, Parabacteroides, Alloprevotella, and Helicobacter, leading to a decrease in interleukin-6 (IL-6). Exposure to the high dose of DEP enriched the butyrate-producing genera, Alloprevotella and Intestinimonas, leading to an increase in estradiol and a resulting decrease in total triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C); meanwhile, DEP-induced increases in peptide tyrosine‒tyrosine (PYY) and ghrelin were attributed to the enrichment of short-chain fatty acid-producing Clostridium sensu stricto 1 and Lactobacillus. These findings indicate that measuring the effects of DEP is not a proxy for measuring the effects of its parent compounds.

scholarly journals Toxicity and Anti-inflammatory Activities of an Extract of the Eleutherine bulbosa Rhizome on Collagen Antibody-induced Arthritis in a Mouse Model

2018 ◽  
Vol 13 (7) ◽  
pp. 1934578X1801300
Author(s):  
Pham Thi Bich Hanh ◽  
Do Thi Thao ◽  
Nguyen Thi Nga ◽  
Ngo Thi Phuong ◽  
Le Ngoc Hung ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ethanol Extract ◽  
Serum Levels ◽  
Negative Control ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Beneficial Effects ◽  
Anti Inflammatory

As a continuation of our interest in the anti-inflammatory activities of Vietnamese plants, we searched for novel anti-inflammatory agents in Eleutherine bulbosa and evaluated the anti-inflammatory effects of an ethanol extract of the rhizome of E. bulbosa (EBE) on lipopolysaccharide-stimulated RAW 264.7 macrophages in vitro and in a collagen antibody-induced arthritic (CAIA) mouse model in vivo. Treatment of the CAIA mice with EBE decreased the incidence of arthritis, especially at a dose of 1000 mg/kg body weight. A significant ( P<0.05) decrease in the arthritis score was seen after high-dose EBE treatment between days 10 and 14 in comparison with the negative control. The serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 in the mice were measured using commercial ELISA kits. The results suggest that an ethanol extract of the E. bulbosa rhizome has beneficial effects on inflammatory cytokine regulation in an experimental CAIA model.

scholarly journals The antiprogestin RU486 dissociates LH and FSH secretion in male rats: evidence for direct action at the pituitary level

1999 ◽  
Vol 160 (2) ◽  
pp. 197-203 ◽  
Author(s):  
JE Sanchez-Criado ◽  
C Bellido ◽  
M Tebar ◽  
A Ruiz ◽  
D Gonzalez
Keyword(s):  
Negative Feedback ◽  
Direct Action ◽  
Serum Levels ◽  
Male Rats ◽  
Pituitary Stalk ◽  
Gonadotrophin Secretion ◽  
Lhrh Antagonist ◽  
Lh Secretion

Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing FSH and decreasing LH secretion. In subsequent experiments we evaluated the involvement of testicular or adrenal secretory products, as well as hypothalamic LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of gonadotrophins. The first day of RU486 injection was designated day 1, subsequent days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii) bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle or were sham operated. To ascertain whether the secretion of LHRH is involved in the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486-treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100 ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000 h on days 2 and 4. Controls were given saline. All animals were decapitated at 1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and testosterone assays.%While ADX had no effect on FSH and LH secretion in either oil- or RU486-treated rats, the removal of androgen negative feedback with flutamide treatment or by ORCH substantially increased serum levels of FSH and LH in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No differences in pituitary stalk plasma LHRH concentrations were found between oil- and RU486-treated rats. Injection of LHRH increased serum FSH and LH concentrations in oil-treated rats but only, and to a lesser extent, LH concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum concentrations of FSH and LH in both oil- and RU486-treated rats. These results suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.

Sign in / Sign up

Export Citation Format

Share Document