Effects Of Histamine Research Articles

GABA-ergic agents modulated the effects of histamine on the behaviour of male mice in the elevated plus maze test.

What is the central question of this study? Is there an interaction between histamine and the GABAergic system in modulation of anxiety in mice? What is the main finding and its importance? There is a synergistic anxiogenic effect between histamine and bicuculline in mice. This effect may be due to a direct or an indirect effect of the histaminergic system on the GABAergic system. It has been documented that both histaminergic and GABAergic systems participate in the neurobiology of anxiety behaviour. In the current research, we investigated the effects of the histaminergic system and GABAA receptor agents on anxiety-related behaviours and their interaction using the elevated plus maze test in mice. Intraperitoneal (i.p.) administration of muscimol (0.12 and 0.25mg/kg) increased the open arm time (OAT) (P<0.001) without affecting the open arm entries (OAE) and locomotor activity, showing an anxiolytic effect. i.p. injection of bicuculline (0.5 and 1mg/kg) decreased OAT (P<0.001) but not OAE and locomotor activity, suggesting an anxiogenic behaviour. Intracerebroventricular (i.c.v.) microinjection of histamine (2.5 and 5μg/mouse) resulted in a decline in OAT (P<0.001) but not OAE and locomotor activity, indicating an anxiogenic response. Co-administration of histamine with GABAergic agents, muscimol (0.06mg/kg; i.p.) and bicuculline (0.25mg/kg; i.p.), decreased (P<0.001) and increased (P<0.05), respectively, the anxiogenic-like response to the effective dose (5μg/mouse; i.c.v.) of histamine. In addition, co-treatment of effective doses of histamine (2.5 and 5μg/mouse;i.c.v.) with an effective dose of muscimol (0.12mg/kg; i.p.) and a non-effective dose of bicuculline (0.25mg/kg; i.p.) significantly decreased OAT (P<0.001), suggesting a likely interaction between the histaminergic and GABAergic systems in the regulation of anxiety. The results demonstrated a synergistic anxiogenic-like effect between histamine and bicuculline in mice. In conclusion, our results present an interaction between the histaminergic and GABAergic systems in anxiolytic/anxiogenic-like behaviours in the elevated plus maze test.

Histamine Sensitization of the Voltage-Gated Sodium Channel Nav1.7 Contributes to Histaminergic Itch in Mice.

Itch, a common clinical symptom of many skin diseases, severely impairs the life quality of patients. Nav1.7, a subtype of voltage-gated sodium channels mainly expressed in primary sensory neurons, is responsible for the amplification of threshold currents that trigger action potential (AP) generation. Gain-of-function mutation of Nav1.7 leads to paroxysmal itch, while pharmacological inhibition of Nav1.7 alleviates histamine-dependent itch. However, the crosstalk between histamine and Nav1.7 that leads to itch is unclear. In the present study, we demonstrated that in the dorsal root ganglion (DRG) neurons from histamine-dependent itch model mice induced by compound 48/80, tetrodotoxin-sensitive (TTX-S) but not TTX-resistant Na+ currents were activated at more hyperpolarized membrane potentials compared to those on DRG neurons from vehicle-treated mice. Meanwhile, bath application of histamine shifted the activation voltages of TTX-S Na+ currents to the hyperpolarized direction, increased the AP frequency, and reduced the current threshold required to elicit APs. Further mechanistic studies demonstrated that selective activation of H1 but not H2 and H4 receptors mimicked histamine effect on TTX-S Na+ channels in DRG neurons. The protein kinase C (PKC) inhibitor GO 8963, but not the PKA inhibitor H89, normalized histamine-sensitized TTX-S Na+ channels. We also demonstrated that histamine shifted the activation voltages of Na+ currents to the hyperpolarized direction in Chinese hamster ovary (CHO) cells expressing Nav1.7. Importantly, selective inhibition of Nav1.7 by PF-05089771 significantly relieved the scratching frequency in a histamine-dependent itch model induced by compound 48/80. Taken together, these data suggest that activation of H1 receptors by histamine sensitizes Nav1.7 channels through the PKC pathway in DRG neurons that contributes to histamine-dependent itch.

Direct effect of lipopolysaccharide and histamine on permeability of the rumen epithelium of steers ex vivo.

Disruption of the ruminal epithelium barrier occurs during subacute ruminal acidosis due to low pH, hyper-osmolality, and increased concentrations of lipopolysaccharide and histamine in ruminal fluid. However, the individual roles of lipopolysaccharide and histamine in the process of ruminal epithelium barriers disruption are not clear. The objective of the present investigation was to evaluate the direct effect of lipopolysaccharide and histamine on the barrier function of the ruminal epithelium. Compared with control (CON), histamine (HIS, 20 μM) increased the short-circuit current (Isc; 88.2%, P < 0.01), transepithelial conductance (Gt; 29.7%, P = 0.056), and the permeability of fluorescein 5(6)-isothiocyanate (FITC) (1.04-fold, P < 0.01) of ruminal epithelium. The apparent permeability of LPS was 1.81-fold higher than HIS (P < 0.01). The mRNA abundance of OCLN in ruminal epithelium was decreased by HIS (1.1-fold, P = 0.047). The results of the present study suggested that mucosal histamine plays a direct role in the disruption of ruminal epithelium barrier function, whereas lipopolysaccharide (at a pH of 7.4) has no effect on the permeability of rumen tissues ex vivo.

Dipotassium Glycyrrhizinate Against Fibrotic Effects of Histamine Depletes Intracellular Glutathione to Discomfort Mitochondrial, Inducing Cell Apoptosis/ Ferroptosis of Over-Activated Lung Fibroblast

Pulmonary fibrosis (PF) is the common outcome of a variety of chronic lung diseases and systemic diseases, and the consequence of Coronavirus Disease 2019 (COVID-19). There is currently a lack of effective treatments to reverse this disease or prevent its development. The purpose of this study is to investigate the effect of dipotassium glycyrrhizinate (DG) on lung fibroblasts and the possible mechanism of alleviating pulmonary fibrosis. Extract primary lung fibroblasts, establish cell models, and use time-lapse photography to continuously monitor the effects of dipotassium glycyrrhizinate and histamine on the morphology of lung fibroblasts. The content of glutathione in cells was detected by the fluorescence method. Cell mitochondrial membrane potential was examined, protein expressions of P53, Caspase-3, Bax and Bal-2 of lung fibroblasts were evaluated by western blot and immune cytochemistry. Our data demonstrated that dipotassium glycyrrhizinate inhibited histamine-induced cell growth/proliferation, glutathione content, mitochondrial membrane potential; also down-regulated P53 and up-regulated the ratio of Bax/Bcl-2, leading to the ferritosis/apoptosis of activated lung fibroblasts, against the fibrotic effects of histamine. Present study provided a new pharmaceutics mechanism of dipotassium glycyrrhizinate for the treatment of lung fibrosis that dipotassium glycyrrhizinate against fibrotic effects of histamine depletes intracellular glutathione to discomfort mitochondrial, inducing cell apoptosis/ferroptosis of over-activated lung fibroblast.

Effects of systemic inflammation and histamine on the network oscillation in the anterior cingulate cortex

Effects of systemic inflammation and histamine on the network oscillation in the anterior cingulate cortex

4-Carvomenthenol, a monoterpene of essential oils, and its underlying effects on anti-inflammatory activity and immediate hypersensitivity reaction

The monoterpene 4-carvomenthenol (Carvo) is found in essential oils of plant. Here, we evaluate the Carvo oral pretreatment in acute inflammatory experimental models and in silico molecular docking. Mice pretreated with Carvo were challenged and submitted to the protocols: paw edema, peritonitis, scratching behavior and anaphylactic shock reaction. Besides, we used histamine H1 receptor, cyclooxygenases (COX-1 and COX-2) and phospholipase A2, as targets for molecular docking analysis. Carvo inhibited the carrageenan-induced paw edema and decreased the peritoneal influx of polymorphonuclear cells on carrageenan-challenged mice without interfering with the mononuclear cell influx. Moreover, Carvo diminished the histamine, PGE2 and compound 48/80 induced paw edematogenic effect. The monoterpene also diminished the mice scratching behavior and, surprisingly, avoided the animal death caused by compound 48/80 in 30 min. Through the docking analysis, Carvo showed favorable binding energy to the histamine H1 receptor. This study demonstrates that Carvo attenuated the allergic inflammatory process, decreasing edema, cell migration, activation of mast cells and the histamine release, probably due to interaction of Carvo with the histamine H1 receptor, ameliorating the itching and the anaphylactic shock reaction. Therefore, the results of this study indicate that Carvo has anti-inflammatory properties by reducing the histamine effects.

Revealing histamine-sensible activity of Wood umbilical cord serum in experiments with ring segments of arteries and umbilical cord vein and with myometrium strips of pregnant women

In experiments with 60 segments of arteries and 46 segments of the umbilical cord vein of 24 newborns and 35 strips of myometrium of 12 pregnant women, the effect of 100-fold dilutions of cord blood serum (SPK-1: 100) on the contractile effects of histamine (0.01, 0.1 and 1 ϻg l ml). SPK-1: - 100 increased the vasoconstrictor and uterostimulating effects of histamine.&#x0D; H1-histaminosensitizing activity of SPK-1: 100 and the efficiency of activation of H1-histamine receptors of myocytes of the arteries and umbilical cord veins are increased in the presence of obstetric complications. A conclusion was made about the content of endogenous sensitizer H1-histamine receptors (ESGR) in the fetal blood, the level of which increases in the presence of obstetric complications, as well as the possible role of histamine and ESGR in the regulation of fetoplacental blood circulation in conditions of normal and pathological conditions.

Histamine enhances ATP-induced itching and responsiveness to ATP in keratinocytes

Mechanical stimulation of cultured keratinocytes and a living epidermis increases intracellular calcium ion concentrations ([Ca2+]i) in stimulated cells. This action propagates a Ca2+ wave to neighboring keratinocytes via ATP/P2Y2 receptors. Recent behavioral, pharmacological studies revealed that exogenous ATP induces itching via P2X3 receptors in mice. We previously showed that alloknesis occurs when an external stimulus is applied to the skin with increased epidermal histamine in the absence of spontaneous pruritus. Based on these results, we investigated the effects of histamine at a concentration that does not cause itching on ATP-induced itching. The mean number of scratching events induced by the mixture of ATP and histamine increased by 28% over the sum of that induced by histamine alone or ATP alone. A317491, a P2X3 receptor antagonist, suppressed the mixture-induced scratching more often than the ATP-induced scratching. Next, we examined the ATP-induced [Ca2+]i change before and after histamine stimulation using normal human epidermal keratinocytes. Some cells did not respond to ATP before histamine stimulation but responded to ATP afterward, the phenomenon suppressed by chlorpheniramine maleate. These findings suggest that histamine enhances ATP-induced itching and that a potential mechanism could involve increased responsiveness to ATP in keratinocytes.

Autochthonous Probiotics Alleviate the Adverse Effects of Dietary Histamine in Juvenile Grouper (Epinephelus coioides).

High dose (0.3%) of dietary histamine can cause adverse effects on growth performance, innate immunity, and gut health in juvenile grouper (Epinephelus coioides). In the present study, three autochthonous probiotics (Bacillus pumilus SE5, Psychrobacter sp. SE6, and Bacillus clausii DE5) were supplemented separately to diets containing 0.3% of histamine and their effects on growth performance, innate immunity, and gut health of grouper (E. coioides) were evaluated in a 56-day feeding trial. The results showed considerable increase in weight gain, specific growth rate, hepatosomatic index, and decreased feed conversion rate in groupers fed with probiotic-supplemented diets. Supplementation of autochthonous probiotics has improved antioxidant capacity and innate immunity of E. coioides by measuring correlative parameters, such as total antioxidant capacity, superoxide dismutase activity, malondialdehyde content, and so on. Additionally, dietary probiotics have significantly reduced the levels of serum interleukin-1β (at days 28 and 56), fatty acid-binding protein 2, and intestinal trefoil factor (at day 28), and promoted intestinal integrity following remarkably increased muscle thickness and mucosal fold height at day 56, especially in grouper fed with B. pumilus SE5 containing diet (P < 0.05). On day 56, the gut microbial composition of E. coioides was positively shaped by autochthonous probiotics, the relative abundance of potentially pathogenic Photobacterium decreased while beneficial Lactobacillus increased in fish fed with probiotic strains, especially with B. pumilus SE5 and B. clausii DE5. These results suggest that among the three autochthonous probiotic strains tested, B. pumilus SE5 is showing better efficiency in alleviating the adverse effects of (high levels) dietary histamine by decreasing the expression of inflammatory markers and by improving the growth, innate immunity, and gut health of juvenile grouper E. coioides.

Optimization of oxidative stress-induced premature senescence model using VH10 fibroblasts for assessment of natural compounds

The diverse physiological functions of histamine are mediated through distinct histamine receptors. In this study we investigated the role of H2R and H4R in the effects of histamine on the production of reactive oxygen species by phagocytes in whole blood.Changes in reactive oxygen species (ROS) production by whole blood phagocytes after treatment with histamine, H4R agonists (4-methylhistamine, VUF8430), H2R agonist (dimaprit) and their combinations with H4R antagonist (JNJ10191584) and H2R antagonist (ranitidine) were determined using the chemiluminescence (CL) assay. To exclude the direct scavenging effects of the studied compounds on the CL response, the antioxidant properties of all compounds were measured using several methods (TRAP, ORAC, and luminol–HRP–H2O2 based CL).Histamine, 4-methylhistamine, VUF8430 and dimaprit inhibited the spontaneous and OZP-activated whole blood CL in a dose-dependent manner. On the other hand, only VUF8430 was able to inhibit PMA-activated whole blood CL. Ranitidine, but not JNJ10191584, completely reduced the effects of histamine, 4-methylhistamine and dimaprit. The direct scavenging ability of tested compounds was negligible.Our results demonstrate that the inhibitory effects of histamine on ROS production in whole blood phagocytes were caused by H2R. Our results also suggest that H4R agonists in concentrations higher than 10− 6 M may also influence ROS production via binding to H2R.

Electrochemical Imaging of Endothelial Permeability Using a Large-Scale Integration-Based Device.

It is important to clarify the transport of biomolecules and chemicals to tissues. Herein, we present an electrochemical imaging method for evaluating the endothelial permeability. In this method, the diffusion of electrochemical tracers, [Fe(CN)6]4–, through a monolayer of human umbilical vein endothelial cells (HUVECs) was monitored using a large-scale integration-based device containing 400 electrodes. In conventional tracer-based assays, tracers that diffuse through an HUVEC monolayer into another channel are detected. In contrast, the present method does not employ separated channels. In detail, a HUVEC monolayer is immersed in a solution containing [Fe(CN)6]4– on the device. As [Fe(CN)6]4– is oxidized and consumed at the packed electrodes, [Fe(CN)6]4– begins to diffuse through the monolayer from the bulk solution to the electrodes and the obtained currents depend on the endothelial permeability. As a proof-of-concept, the effects of histamine on the monolayer were monitored. Also, an HUVEC monolayer was cocultured with cancer spheroids, and the endothelial permeability was monitored to evaluate the metastasis of the cancer spheroids. Unlike conventional methods, the device can provide spatial information, allowing the interaction between the monolayer and the spheroids to be monitored. The developed method is a promising tool for organs-on-a-chip and drug screening in vitro.

EVALUATION OF ANTI-ASTHMATIC ACTIVITY OF ETHANOLIC EXTRACT OF CYNODON DACTYLON LEAVES

In the present study Cynodon dactylon leaves ethanolic extract and its chloroform and ethyl acetate fractions were used to evaluate the anti-asthmatic activity, using various experimental in vivo and in vitro animal models. Ethanolic extract of Cynodon dactylon and its chloroform and ethyl acetate fractions were evaluated for its anti-asthmatic activity by in vitro models (isolated guinea pig ileum preparation and isolated guinea pig tracheal chain preparation) in vivo models (Histamine and acetylcholine induced bronchospasm in guinea pigs and milk induced eosinophilia in mice model). Ethanolic extract of Cynodon dactylon and its ethyl acetate fraction at the concentration of 10 mg significantly antagonized the effect of histamine induced contraction on isolated guinea pig ileum preparation. Ethyl acetate fraction of Cynodon dactylon showed the maximum spasmolytic activity and significantly extended the latent period of convulsion as compared to standard (Ketotifen fumarate) upon histamine and acetylcholine exposure in a dose dependent manner. The study concluded that, chloroform and ethyl acetate fractions of Cynadon dactylon was shown significant anti-asthmatic activity.

Impact of Biogenic Amines on the Growth of Green Microalgae

Background: The goal of this research project was to test various neuroactive amines in the capacity of growth stimulators/accelerators of the green microalgae Scenedesmus quadricauda and Chlorella vulgaris that have much biotechnological potential because they can be used for producing drugs, food ingredients, cosmetics, and biofuel. The issue of the ecological role of the biogenic amines in terms of interspecies communication in aqueous ecosystems was also addressed in this work. Methods: S. quadricauda strain GEHD and C. vulgaris strain ALP were cultivated in the light with constant aeration at 24oC in a minerals-containing medium. Experimental systems contained 1, 10 or 100 mM of dopamine hydrochloride, histamine hydrochloride, norepinephrine hydrochloride, or serotonin hydrochloride that were added at inoculation as freshly prepared aqueous solutions. Algal cells were counted using a light microscope , and their number in 1 mL of culture was calculated. The culture liquid and sonicated biomass of S. quadricauda and C. vulgaris were tested for the presence of endogenous amines using high-performance liquid chromatography (HPLC) with an amperometric detector. Results: The biogenic amines serotonin, norepinephrine, dopamine, and histamine significantly stimulated the growth of S. quadricauda, at concentrations of 1 and/or 10 mM but not 100 mM. Histamine was the most efficient stimulator, causing an average 65% increase in biomass accumulation at the end of the cultivation period. The effects of serotonin, dopamine and histamine on C. vulgaris were reported in our previous publication [1], but this work contains the results of our experiments with the previously untested norepinephrine that slightly stimulated the growth of C. vulgaris. HPLC analysis failed to reveal any endogenous amines in the culture liquid and biomass of both microalgae. Conclusions: Since biogenic amines stimulate the growth of the microalgae S. quadricauda and C. vulgaris but are not synthesized by them, we suggest that the algae normally respond to amines produced by other components of aqueous ecosystems, including zooplankton and fish that are known to release significant amounts of biogenic amines into the environment. The data obtained hold some promise with regard to developing a relatively economical technique of boosting algal biomass production.

A novel biosensing of histamine based on liquid crystal through dielectric and electro-optical approaches

The effects of histamine on blood vessels play a key role in immune response at the time of physical damage or some allergic reaction. The prevalent measurement methods for the detection of histamine are amperometric and capacitive biosensor techniques. Here, we present an easy fabrication and optimization studies of a novel liquid crystal (LC) based biosensor capable of detecting histamine level. The proposed biosensor is based on the orientational transition of nematic LC (NLC), 4′-octyl-4-biphenylcarbonitrile by enzymatic reaction of biomolecules. The sensing mechanism is based on homeotropic-to-planar configurational change of long molecular axes of LC when diamine oxidase/histamine was immobilized on the pretreated glass substrate. The developed LC-based histamine biosensor provides a good optical and dielectric response at a detection limit of 20 mg/L–500 mg/L.

H1-Receptor Antagonist Olopatadine Inhibits MUC5AC Secretion by Conjunctival Goblet Cells.

The study examined the effect of H1-receptor antagonist olopatadine on the secretory function of cultured rat conjunctival goblet cells (CGC) assessed by enzyme-linked lectin assay employing UEA-I lectin. The level of mRNA for membrane-bound protein MUC16 in histaminestimulated CGC was assayed by reverse transcription PCR in the control and after preliminary application of olopatadine. The intracellular calcium concentration [Ca2+]i was measured by the calcium colorimetric method using GENMED kits. The effects of histamine and olopatadine on p-ERK level were assessed by Western blotting. Histamine up-regulated secretion of mucin MUC5AC and expression of membrane-bound protein MUC16 in CGC. In addition, it increased both [Ca2+]i and the level of phosphorylated ERK. These effects were diminished by preliminary application of olopatadine that probably acted via the ERK signaling pathway. Thus, olopatadine reduced [Ca2+]i and down-regulated ERK phosphorylation by binding to H1-receptors, thereby inhibiting secretion of mucin from histamine-stimulated CGC.

Functional interaction of H2-receptors and 5HT4-receptors in atrial tissues isolated from double transgenic mice and from human patients

In the past, we generated transgenic mice that overexpress the human histamine 2 (H2)-receptor (H2-TG) or that overexpress the human serotonin 4 (5-HT4)-receptor (5-HT4-TG) in the heart. Here, we crossbred these lines of mice to generate double transgenic mice that overexpress both receptors (DT). This was done to study a conceivable interaction between these receptors in the mouse heart as a model for the human heart. When in left atria, initially, force of contraction was elevated maximally with 1 µM serotonin, and subsequently, histamine was cumulatively applied; a biphasic effect of histamine was noted: the force of contraction initially decreased, maximally at 10 nM histamine, and thereafter, the force of contraction increased again at 1 µM histamine. Notably, functional interaction between 5-HT and histamine was also identified in isolated electrically stimulated trabeculae carneae from human right atrium (obtained during cardiac surgery). These functional and biochemical data together are consistent with a joint overexpression of inotropically active H2-receptors and 5-HT4-receptors in the same mouse heart. We also describe an antagonistic interaction on the force of contraction of both receptors in the mouse atrium (DT) and in the human atrial muscle strips. We speculate that via this interaction, histamine might act as a “brake” on the cardiac actions of 5-HT via inhibitory GTP-binding proteins acting on the activity of adenylyl cyclase.

Активність ферментів антиоксидантного захисту і вміст глутатіону у плазмі крові щурів за дії кверцетину та гістаміну в дослідах in vitro

The effect of histamine and quercetin, as well as their combined effect on the activity of superoxide dismutase, catalase and the content of reduced glutathione in the blood plasma of rats was studied. It was found that the addition to the blood of quercetin at a concentration of 0.1; 0.3; 0.5; 1.0; 5.0 mM causes an increase in superoxide dismutase activity. It was found that histamine at concentrations of .01 and 0.1 μm leads to a decrease in superoxide dismutase activity by 31 and 17 %, respectively. Whereas the biogenic amine in the lowest and highest concentrations does not change the activity of superoxide dismutase in plasma. At simultaneous introduction into blood of histamine in the maximum concentration (10.0 μm) and quercetin in concentration of 0,1; 0.5; 3.0 mM normalizes the activity of superoxide dismutase. And only the combined action of histamine of this concentration and quercetin at a concentration of 5.0 mM reduces the activity of the enzyme by 21 %. Histamine at a concentration of 0.01 μm and the simultaneous action of quercetin at a concentration of 0.1; 0.5; 3.0; 5.0 mM increases the activity of superoxide dismutase, which indicates the generation of reactive oxygen species, in particular the superoxide anion radical. It was found that the addition of whole concentrations of quercetin to whole blood causes a decrease in plasma catalase activity. The combined action of quercetin and histamine causes a decrease in catalase activity. It was found that the addition to the blood of quercetin at a concentration of 0.1; 0.3; 0.5; 1.0 mM causes a decrease in the content of reduced glutathione. Quercetin at a concentration of 3.0 and 5.0 mM causes an increase in reduced glutathione by 27 and 14 %, respectively, compared to the reference plasma. Histamine at concentrations of 10.0, 1.0 and 0.01 μm leads to an increase in the amount of reduced glutathione by 24, 26 and 19 %, respectively. And at a concentration of 0.1 μm, the biogenic amine reduces the GSH content by 39 %. With simultaneous introduction into the blood of histamine at a concentration of 10.0 μm and quercetin at a concentration of 0.1; 0.5; 3.0 mM there is an increase in the content of reduced glutathione. And only at a concentration of 5.0 mM quercetin on the background of the action of histamine (10.0 μm), the content of reduced glutathione is slightly reduced. However, with the combined action of histamine at a minimum concentration (0.01 μM) and quercetin at a concentration of 0.1; 0.5; 3.0 and 5.0 mM there is a decrease in the content of reduced glutathione. After performing a dispersion analysis, it was found that the state of the antioxidant system, both enzymatic and non-enzymatic, is significantly affected by histamine. The smallest, but significant share of the effect is on the action of quercetin in the blood plasma of rats. The indirect and significant effect of the simultaneous action of histamine and quercetin on the antioxidant system of rat plasma was revealed.

Effect of dietary histamine on intestinal morphology, inflammatory status, and gut microbiota in yellow catfish (Pelteobagrus fulvidraco)

The toxic effect of dietary histamine on the intestine of aquatic animals has been demonstrated, but reports on the morphological observation of the intestine are limited. Thus, a feeding trial was conducted to determine the effect of dietary histamine on intestinal histology, inflammatory status and gut microbiota of yellow catfish (Pelteobagrus fulvidraco). Here, we showed that histamine-rich diets caused severe abnormality and damage to the intestine, including a decreased villi length and reduced villi number. In addition, the quantitative real-time PCR (qRT-PCR) demonstrates that histamine-rich diets increased the expression of pro-inflammatory genes (Tnfα, Il1β, and Il8) and decreased the expression of an anti-inflammatory gene (Il10). Furthermore, the alpha-diversity (observed OTUs, Chao1, Shannon and Simpson) and beta-diversity (non-metric multidimensional scaling, with the stress value of 0.17) demonstrated that histamine-rich diets caused alterations in gut microbiota composition and diversity. Co-occurrence networks analysis of the gut microbiota community showed that the histamine influenced the number and the relationship between bacteria species in the phyla of Acidobacteria, Proteobacteria, and Bacteroidetes, which caused the instability of the intestinal microbiota community. Additionally, random forest selected six bacterial species as the biomarkers to separate the three groups, which are Lachnospiraceae Blautia (V520), Bacteroidales S24.7 (V235), Chloroplast Streptophyta (V368), Actinomycetales Streptomycetaceae (V152), Clostridia Clostridiales (V491) and Paraprevotellaceae Prevotella (V245). Finally, Pearson correlation analysis demonstrated that V520, V235, and V491 were negatively correlated with pro-inflammatory factors (Tnfα, Il1β, and Il8) and positively correlated with an anti-inflammatory factor (Il10), which indicated that V520, V235, and V491 might be anti-inflammatory. These findings improved our understanding of the toxic effect of dietary histamine to intestinal histological damage, the induction of mucosa inflammatory status, and the alteration of gut microbiota.

Effects of histamine and various histamine receptor antagonists on gene expression profiles of macrophages during compressive strain.

PurposeTissue hormone histamine can accumulate locally within the periodontal ligament via nutrition or may be released during allergic reactions by mast cells, which may have an impact on orthodontic tooth movement. In addition to periodontal ligament fibroblasts, cells of the immune system such as macrophages are exposed to compressive strain. The aim of this study was thus to investigate the impact of histamine on the gene expression profile of macrophages in the context of simulated orthodontic compressive strain.MethodsMacrophages were incubated with different histamine concentrations (50, 100, 200 µM) for 24 h and then either left untreated or compressed for another 4 h. To assess the role of different histamine receptors, we performed experiments with antagonists for histamine 1 receptor (cetirizine), histamine 2 receptor (ranitidine) and histamine 4 receptor (JNJ7777120) under control and pressure conditions. We tested for lactate dehydrogenase release and analyzed the expression of genes involved in inflammation and bone remodeling by reverse transcription quantitative polymerase chain reaction (RT-qPCR).ResultsHistamine elevated gene expression of tumor necrosis factor under control conditions and in combination with pressure application. Increased prostaglandin-endoperoxide synthase‑2 mRNA was observed when histamine was combined with compressive force. Interleukin‑6 gene expression was not affected by histamine treatment. In macrophages, compressive strain increased osteoprotegerin gene expression. Histamine further elevated this effect. Most of the observed histamine effects were blocked by the histamine 1 receptor antagonist cetirizine.ConclusionsHistamine has an impact on the gene expression profile of macrophages during compressive strain in vitro, most likely having an impairing effect on orthodontic tooth movement by upregulation of osteoprotegerin expression.

Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors.

Histamine is involved in the regulation of collagen metabolism during healing following a myocardial infarction; however, its effects on the intact heart tissue is unknown. The aim of the present study was to determine whether histamine may influence collagen content in cells isolated from intact heart, and to identify the histamine receptor involved in the regulation of collagen deposition. Cells were isolated from intact rat hearts and subjected to identification by flow cytometry. The effects of histamine and its receptor agonists and antagonists were investigated. The heart cells were found to be actin, desmin and vimentin positive. Histamine (used at a concentrations of 1x10-10-1x10-5 M) increased collagen content within the culture and increased the expression of α1 chain of the procollagen type III gene. The H2, H3 and H4 receptor inhibitors ranitidine, ciproxifan and JNJ 7777120 blocked the effect of histamine on collagen content. All tested histamine receptor agonists, viz. 2-pyridylethylamine dihydrochloride (H1 receptor agonist), amthamine dihydrobromide (H2 receptor agonist), imetit (H3 receptor agonist) and 4-methylhistamine hydrochloride (H4 receptor agonist), elevated collagen content within the heart myofibroblast cultures. The cells isolated from the intact heart were identified as myofibroblasts. Thus, the results of the present study showed that histamine augmented collagen content in the heart myofibroblast culture by activation of three histamine receptors (H2, H3 and H4). The effect of the amine was also dependent on the activation of collagen type III gene expression.