scholarly journals Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 251 ◽  
Author(s):  
Bernadette Lázár ◽  
Gábor Brenner ◽  
András Makkos ◽  
Mihály Balogh ◽  
Szilvia László ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Mucosal Damage ◽  
Inhibitory Effect ◽  
Intestinal Dysbiosis ◽  
Bowel Diseases ◽  
Direct Inhibitory Effect ◽  
Cox 2 ◽  
Small Intestinal

Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it.

scholarly journals 2,4-EPIBRASSIONOLIDE ACTIVATES PRIMING RESISTANCE AGAINST RHIZOPUS STOLONIFER INFECTION IN PEACH FRUIT

2020 ◽  
Vol 49 (2) ◽  
pp. 135-143
Author(s):  
C.H. Li ◽  
M.Y. Du ◽  
K.T. Wang
Keyword(s):  
Fungal Infection ◽  
Inhibitory Effect ◽  
The Other ◽  
Antifungal Compounds ◽  
Rhizopus Stolonifer ◽  
Peach Fruit ◽  
Direct Inhibitory Effect ◽  
Potential Alternative ◽  
Direct Toxicity

This study was conducted to assess the effects of 2,4-epibrassionolide (EBR) on mold decay caused by Rhizopus stolonifer and its capability to activate biochemical defense reactions in postharvest peaches. The treatment of EBR at 5 μM possessed the optimum effectiveness on inhibiting the Rhizopus rot in peach fruit among all treatments. The EBR treatment significantly up-regulated the expression levels of a set of defense-related enzymes and PR genes that included PpCHI, PpGns1, PpPAL, PpNPR1, PpPR1 and PpPR4 as well as led to an enhancement for biosynthesis of phenolics and lignins in peaches during the incubation at 20 °C. Interestingly, the EBR-treated peaches exhibited more striking expressions of PR genes and accumulation of antifungal compounds upon inoculation with the pathogen, indicating a priming defense could be activated by EBR. On the other hand, 5 μM EBR exhibited direct toxicity on fungal proliferation of R. stolonifer in vitro. Thus, we concluded that 5 μM EBR inhibited the Rhizopus rot in peach fruit probably by a direct inhibitory effect on pathogen growth and an indirect induction of a priming resistance. These findings provided a potential alternative for control of fungal infection in peaches during the postharvest storage.

scholarly journals Dietary ascorbic acid lowers the concentration of soluble copper in the small intestinal lumen of rats

1994 ◽  
Vol 71 (5) ◽  
pp. 701-707 ◽  
Author(s):  
G. J. Van Den Berg ◽  
S. YU ◽  
A. G. Lemmens ◽  
A. C. Beynen
Keyword(s):  
Ascorbic Acid ◽  
Small Intestine ◽  
Liquid Phase ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Intestinal Lumen ◽  
Distal Intestine ◽  
Small Intestinal ◽  
Ascorbic Acid Supplementation

We tested the hypothesis that ascorbic acid in the diet of rats lowers the concentration of soluble Cu in the small intestine, causing a decrease in apparent Cu absorption. Male rats were fed on diets adequate in Cu (5 mg Cu/kg) without or with 10 g ascorbic acid/kg. The diet with ascorbic acid was fed for either 6 or 42 d. Ascorbic acid depressed tissue Cu concentrations after a feeding period of 42, but not after 6 d. Dietary ascorbic acid lowered apparent Cu absorption after 6, but not after 42 d. The lowering of tissue Cu concentrations after long-term ascorbic acid feeding may have increased the efficiency of Cu absorption, and thus counteracted the inhibitory effect of ascorbic acid. Dietary ascorbic acid caused a significant decrease in the Cu concentrations in the liquid phase of both the proximal and distal parts of the small intestinal lumen. This effect was due to both a decrease in the amount of Cu in the liquid digesta and an increase in the volume of the liquid phase; only the latter effect for the distal intestine was statistically significant. We conclude that ascorbic acid supplementation lowers Cu absorption by decreasing the concentration of soluble Cu in the small intestine.

scholarly journals Selective Inhibition of Coxiella burnetii Replication by the Steroid Hormone Progesterone

2020 ◽  
Vol 88 (12) ◽  
Author(s):  
Zachary P. Howard ◽  
Anders Omsland
Keyword(s):  
Coxiella Burnetii ◽  
Efflux Pump ◽  
Q Fever ◽  
Steroid Hormone ◽  
Natural Infection ◽  
Placental Tissue ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Content Type ◽  
Direct Inhibitory Effect

ABSTRACT Coxiella burnetii is a zoonotic bacterial obligate intracellular parasite and the cause of query (Q) fever. During natural infection of female animals, C. burnetii shows tropism for the placenta and is associated with late-term abortion, at which time the pathogen titer in placental tissue can exceed one billion bacteria per gram. During later stages of pregnancy, placental trophoblasts serve as the major source of progesterone, a steroid hormone known to affect the replication of some pathogens. During infection of placenta-derived JEG-3 cells, C. burnetii showed sensitivity to progesterone but not the immediate precursor pregnenolone or estrogen, another major mammalian steroid hormone. Using host cell-free culture, progesterone was determined to have a direct inhibitory effect on C. burnetii replication. Synergy between the inhibitory effect of progesterone and the efflux pump inhibitors verapamil and 1-(1-naphthylmethyl)-piperazine is consistent with a role for efflux pumps in preventing progesterone-mediated inhibition of C. burnetii activity. The sensitivity of C. burnetii to progesterone, but not structurally related molecules, is consistent with the ability of progesterone to influence pathogen replication in progesterone-producing tissues.

scholarly journals Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1497-1504 ◽  
Author(s):  
VF Quesniaux ◽  
GJ Graham ◽  
I Pragnell ◽  
D Donaldson ◽  
SD Wolpe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Inhibitory Effect ◽  
In Vivo Model ◽  
Hematopoietic Progenitors ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Abstract A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5-FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst- forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP- 1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors.

Role of endothelial cells in regulating hemoglobin-induced changes in lymphatic pumping

1992 ◽  
Vol 263 (6) ◽  
pp. H1880-H1887 ◽  
Author(s):  
R. M. Elias ◽  
J. Eisenhoffer ◽  
M. G. Johnston
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Inhibitory Effect ◽  
Direct Inhibitory Effect ◽  
Induced Changes ◽  
Lymphatic Pumping ◽  
Pumping Activity

Studies with a sheep isolated duct preparation in vivo demonstrated that the route of administration of hemoglobin was important in demonstrating its inhibitory effect on lymphatic pumping. With autologous oxyhemoglobin administered intravenously (final plasma concentration 5 x 10(-5) M), pumping was not inhibited. However, the addition of oxyhemoglobin (5 x 10(-5) M) into the reservoir (lumen of the duct) resulted in > 95% inhibition of pumping. The extraluminal administration of oxyhemoglobin (10(-5) M) to bovine mesenteric lymphatics in vitro resulted in a 40% inhibition of pumping, whereas the introduction of oxyhemoglobin (10(-5) M) into the lumen of the vessels suppressed pumping 95%. In vessels mechanically denuded of endothelium, intraluminal oxyhemoglobin inhibited pumping 50%. These results suggested that oxyhemoglobin depressed pumping through an effect on both smooth muscle and endothelium. Once pumping was inhibited with oxyhemoglobin administration, stimulation of the duct with elevations in transmural pressure restored pumping activity when endothelial cells were present. However, in the absence of endothelium, pumping decreased with increases in distending pressures. We conclude that oxyhemoglobin has a direct inhibitory effect on lymphatic smooth muscle. The ability of oxyhemoglobin to alter the pressure range over which the lymph pump operates appears to be dependent on an intact endothelium.

scholarly journals PPARγAgonists as an Anti-Inflammatory Treatment Inhibiting Rotavirus Infection of Small Intestinal Villi

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Dory Gómez ◽  
Natalia Muñoz ◽  
Rafael Guerrero ◽  
Orlando Acosta ◽  
Carlos A. Guerrero
Keyword(s):  
Host Cell ◽  
Cellular Proteins ◽  
Proinflammatory Response ◽  
Intestinal Villi ◽  
Rotavirus Infection ◽  
Infectious Virion ◽  
Cox 2 ◽  
Small Intestinal

Rotavirus infection has been reported to induce an inflammatory response in the host cell accompanied by the increased expression or activation of some cellular molecules including ROS, NF-κB, and COX-2. PPARγstimulation and N-acetylcysteine (NAC) treatment have been found to interfere with viral infections including rotavirus infection. Small intestinal villi isolated fromin vivoinfected mice with rotavirus ECwt were analyzed for the percentage of ECwt-infected cells, the presence of rotavirus antigens, and infectious virion yield following treatment with pioglitazone. Isolated villi were also infectedin vitroand treated with PPARγagonists (PGZ, TZD, RGZ, DHA, and ALA),all-transretinoic acid (ATRA), and NAC. After treatments, the expression of cellular proteins including PPARγ, NF-κB, PDI, Hsc70, and COX-2 was analyzed using immunochemistry, ELISA, immunofluorescence, and Western blotting. The results showed that rotavirus infection led to an increased accumulation of the cellular proteins studied and ROS. The virus infection-induced accumulation of the cellular proteins studied and ROS was reduced upon pioglitazone treatment, causing also a concomitant reduction of the infectious virion yield. We hypothesized that rotavirus infection is benefiting from the induction of a host cell proinflammatory response and that the interference of the inflammatory pathways involved leads to decreased infection.

Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not inhibit acid secretion or motility

1997 ◽  
Vol 273 (1) ◽  
pp. G112-G117 ◽  
Author(s):  
C. McKenzie ◽  
T. Marchbank ◽  
R. J. Playford ◽  
W. Otto ◽  
L. Thim ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Mucosal Damage ◽  
Inhibitory Effect ◽  
Gastric Mucosal Damage ◽  
Conscious Rat ◽  
Immature Rat ◽  
Trefoil Peptide ◽  
Spasmolytic Polypeptide ◽  
Evoked Contractions

The objectives of these studies were to examine whether the trefoil peptide porcine pancreatic spasmolytic polypeptide (PSP) had gastric mucosal protectant properties similar to its human equivalent human spasmolytic polypeptide (hSP) and to confirm the antisecretory and antimotility action of the peptide. PSP and recombinant hSP reduced gastric mucosal damage caused by a combination of subcutaneous indomethacin and restraint stress in the conscious rat. At a dose of 500 micrograms/kg bolus plus 500 micrograms.kg-1.h-1 sc, PSP significantly reduced the total area of damage by 58%. PSP at a dose of 150 micrograms/kg iv had no inhibitory effect on pentagastrin-stimulated gastric acid secretion in the perfused stomachs of anesthetized rats. This lack of antisecretory activity was confirmed in vitro using an isolated stomach preparation from the immature rat. PSP and hSP at concentrations up to 800 nM did not inhibit electrically or chemically evoked contractions of the guinea pig ileum and duodenum in vitro. Thus antisecretory and antimotility actions do not underlie the mucosal protectant properties of PSP. PSP did, however, stimulate cell migration, and this may, at least in part, account for its protectant properties.

scholarly journals α-Mangostin fromCratoxylum arborescens(Vahl) Blume Demonstrates Anti-Ulcerogenic Property: A Mechanistic Study

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Heyam M. A. Sidahmed ◽  
Siddig Ibrahim Abdelwahab ◽  
Syam Mohan ◽  
Mahmood Ameen Abdulla ◽  
Manal Mohamed Elhassan Taha ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
Inhibitory Effect ◽  
Mechanistic Study ◽  
Gastric Lesions ◽  
Property A ◽  
Hsp70 Protein ◽  
Cox 2 ◽  
H Pylori ◽  
Asian Herbal Medicine

Cratoxylum arborescens(Vahl) Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s) ofα-mangostin (AM) in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation ofC. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and nonprotein sulfhydryl groups (NP-SH) were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitory effect, and antioxidant activity of AM were also investigatedin vitro. AM (10 and 30 mg/kg) inhibited significantly (P<0.05) ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC) of AM showed an effectivein vitroanti-H. pyloriactivity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity ofα-mangostin.

Homologous and heterologous regulation of somatostatin-binding sites on chicken adenohypophysial membranes

1990 ◽  
Vol 127 (3) ◽  
pp. 417-425 ◽  
Author(s):  
S. Harvey ◽  
J. S. Baidwan ◽  
D. Attardo
Keyword(s):  
Pituitary Gland ◽  
Binding Sites ◽  
Recombinant Dna ◽  
Inhibitory Effect ◽  
Partial Recovery ◽  
Caudal Lobe ◽  
Direct Inhibitory Effect ◽  
Pituitary Glands

ABSTRACT Binding of 125I-labelled [Tyr1]-somatostatin (125I-[Tyr1]-SRIF) to pituitary caudal lobe membranes was suppressed in immature chickens 1 and 2 h after i.v. administration of unlabelled SRIF at concentrations of 1–100 μg/kg. In-vitro preincubation of chicken pituitary glands for 0·5–4·0 h with 0·1 μmol SRIF/l similarly reduced the binding of 125I-[Tyr1]-SRIF to caudal lobe membrane preparations. After a 4-h incubation in 0·1 mmol SRIF/l, the withdrawal of SRIF from the incubation media was accompanied 4 h later by a partial recovery in the binding of 125I-[Tyr1]-SRIF to pituitary membranes. Passive immunoneutralization of endogenous SRIF resulted in a prompt (within 1 h) and sustained (for at least 24 h) suppression of 125I-[Tyr1]-SRIF binding to pituitary membranes. The i.m. administration of cysteamine (300 mg/kg) to 12-week-old birds depleted hypothalamic SRIF stores and decreased the density of 125I-[Tyr1]-SRIF-binding sites in the caudal and cephalic lobes of the chicken pituitary gland. The reduction in SRIF content and in SRIF-binding sites occurred within 1 h of cysteamine administration and was maintained for at least 24 h. In 6-week-old birds, cysteamine (300 mg/kg) administration suppressed pituitary binding of 125I-[Tyr1]-SRIF for at least 5 days. Circulati concentrations of GH were markedly decreased 1 and 4 h after cysteamine injection, but not after 24 h. Pituitary binding sites for 125I-[Tyr1]-SRIF were not affected by pretreatment of pituitary glands for 2–12 h in vitro with thyroxine or oestradiol-17β (1 nmol/l–10 μmol/l) or with ovine GH or recombinant DNA-derived chicken GH (1–100 μg/ml in vitro and 100–1000 μg/kg in vivo). Ovine prolactin, at concentrations of 1–100 μg/ml was also without effect on 125I-[Tyr1]-SRIF binding to pituitary membranes following a 2- or 4-h incubation with pituitary glands. Pituitary binding sites for 125I-[Tyr1]-SRIF were, however, increased after a 24-h incubation with 1 μmol tri-iodothyronine (T3)/l in vitro and 4 and 24 h after the administration of T3 (100–1000 μg/kg) in vivo. Although T3 had no direct inhibitory effect on 125I-[Tyr1]-SRIF binding to pituitary membranes, binding was suppressed 1 and 2 h after the in-vivo administration of T3 at concentrations of 100–1000 μg/kg. These results therefore demonstrate homologous and heterologous regulation of SRIF-binding sites in the chicken pituitary gland. Journal of Endocrinology (1990) 127, 417–425

scholarly journals Direct Inhibitory Effect of Estrogen on the Human Testis in Vitro

1988 ◽  
Vol 20 (2) ◽  
pp. 131-135 ◽  
Author(s):  
M. Namiki ◽  
M. Kitamura ◽  
N. Nonomura ◽  
H. Sugao ◽  
M. Nakamura ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Human Testis ◽  
Direct Inhibitory Effect
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