Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic. Therefore, the search for compounds with significant immunobiological properties but with decreased cytotoxicities suitable for use in immune-based pharmacotherapy is ongoing. Therefore, we extended our previous investigation of the immunobiological effects of trilobolide to a series of structurally related guaianolides and germacranolides. To evaluate the relationship, we tested a series of selected derivatives containing α-methyl lactone or exomethylene lactone ring. For a wider comparison, we also included some of their glycosidic derivatives. We assessed the in vitro immunobiological effects of the tested compounds on nitric oxide (NO) production, cytokine secretion, and prostaglandin E2 (PGE2) release by mouse peritoneal cells, activated primarily by lipopolysaccharide (LPS), and evaluated their viability. The inhibitory effects of the apparently most active substance, 8-deoxylactucin, seem to be the most promising.

• Klíčová slova
• 8-deoxylactucin, 8-epiisoamberboin, germacranolides, guaianolides, immune-modulatory effects,
• MeSH
• butyráty MeSH
• cytokiny metabolismus   MeSH
• dinoproston metabolismus   biosyntéza   MeSH
• furany MeSH
• laktony * farmakologie   chemie   MeSH
• lipopolysacharidy farmakologie   MeSH
• myši MeSH
• oxid dusnatý * metabolismus   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• seskviterpeny germakranové * farmakologie   chemie   MeSH
• seskviterpeny guajanové * farmakologie   chemie   MeSH
• seskviterpeny farmakologie   chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• butyráty MeSH
• cytokiny MeSH
• dinoproston MeSH
• furany MeSH
• germacranolide MeSH Prohlížeč
• laktony * MeSH
• lipopolysacharidy MeSH
• oxid dusnatý * MeSH
• seskviterpeny germakranové * MeSH
• seskviterpeny guajanové * MeSH
• seskviterpeny MeSH
• trilobolide MeSH Prohlížeč

Saponins, a diverse group of natural compounds, offer an interesting pool of derivatives with biomedical application. In this study, three structurally related spirostanol saponins were isolated and identified from the leek flowers of Allium porrum L. (garden leek). Two of them were identical with the already known leek plant constituents: aginoside (1) and 6-deoxyaginoside (2). The third one was identified as new component of A. porrum; however, it was found identical with yayoisaponin A (3) obtained earlier from a mutant of elephant garlic Allium ampeloprasun L. It is a derivative of the aginoside (1) with additional glucose in its glycosidic chain, identified by MS and NMR analysis as (2α, 3β, 6β, 25R)-2,6-dihydroxyspirostan-3-yl β-D-glucopyranosyl-(1 → 3)-β-D-glucopranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl]-(1 → 4)-β-D-galactopyranoside, previously reported also under the name alliporin. The leek native saponins were tested together with other known and structurally related saponins (tomatonin and digitonin) and with their related aglycones (agigenin and diosgenin) for in vitro cytotoxicity and for effects on NO production in mouse peritoneal cells. The highest inhibitory effects were exhibited by 6-deoxyaginoside. The obtained toxicity data, however, closely correlated with the suppression of NO production. Therefore, an unambiguous linking of obtained bioactivities of saponins with their expected immunobiological properties remained uncertain.

• Klíčová slova
• Allium porrum, NO production, aginoside, alliporin, cytotoxicity, leek flowers, steroid saponins,
• MeSH
• Allium chemie   MeSH
• buněčné linie MeSH
• květy chemie   MeSH
• lipopolysacharidy antagonisté a inhibitory   farmakologie   MeSH
• molekulární konformace MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oxid dusnatý antagonisté a inhibitory   biosyntéza   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• saponiny chemie   izolace a purifikace   farmakologie   MeSH
• spirostany chemie   izolace a purifikace   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipopolysacharidy MeSH
• oxid dusnatý MeSH
• saponiny MeSH
• spirostany MeSH

In vitro models are often used for studying macrophage functions, including the process of phagocytosis. The application of primary macrophages has limitations associated with the individual characteristics of animals, which can lead to insufficient standardization and higher variability of the obtained results. Immortalized cell lines do not have these disadvantages, but their responses to various signals can differ from those of the living organism. In the present study, a comparative proteomic analysis of immortalized PMJ2-R cell line and primary peritoneal macrophages isolated from C57BL/6 mice was performed. A total of 4005 proteins were identified, of which 797 were quantified. Obtained results indicate significant differences in the abundances of many proteins, including essential proteins associated with the process of phagocytosis, such as Elmo1, Gsn, Hspa8, Itgb1, Ncf2, Rac2, Rack1, Sirpa, Sod1, C3, and Msr1. These findings indicate that outcomes of studies utilizing PMJ2-R cells as a model of peritoneal macrophages should be carefully validated. All MS data are deposited in ProteomeXchange with the identifier PXD022133.

• Klíčová slova
• LC-MS/MS, PMJ2-R, peritoneal macrophages, phagocytosis, proteome,
• MeSH
• down regulace MeSH
• fagocytóza MeSH
• genová ontologie MeSH
• kultivované buňky MeSH
• mapy interakcí proteinů MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• peritoneální makrofágy metabolismus   MeSH
• proteom metabolismus   MeSH
• proteomika * MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteom MeSH

Superparamagnetic iron oxide nanoparticles (SPIOn) are widely used as a contrast agent for cell labeling. Macrophages are the first line of defense of organisms in contact with nanoparticles after their administration. In this study we investigated the effect of silica-coated nanoparticles (γ-Fe2O3-SiO2) with or without modification by an ascorbic acid (γ-Fe2O3-SiO2-ASA), which is meant to act as an antioxidative agent on rat peritoneal macrophages. Both types of nanoparticles were phagocytosed by macrophages in large amounts as confirmed by transmission electron microscopy and Prusian blue staining, however they did not substantially affect the viability of exposed cells in monitored intervals. We further explored cytotoxic effects related to oxidative stress, which is frequently documented in cells exposed to nanoparticles. Our analysis of double strand breaks (DSBs) marker γH2AX showed an increased number of DSBs in cells treated with nanoparticles. Nanoparticle exposure further revealed only slight changes in the expression of genes involved in oxidative stress response. Lipid peroxidation, another marker of oxidative stress, was not significantly affirmed after nanoparticle exposure. Our data indicate that the effect of both types of nanoparticles on cell viability, or biomolecules such as DNA or lipids, was similar; however the presence of ascorbic acid, either bound to the nanoparticles or added to the cultivation medium, worsened the negative effect of nanoparticles in various tests performed. The attachment of ascorbic acid on the surface of nanoparticles did not have a protective effect against induced cytotoxicity, as expected.

• Klíčová slova
• Cytotoxicity, Macrophages, Nanoparticles, Oxidative stress,
• MeSH
• antioxidancia metabolismus   toxicita   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kyselina askorbová metabolismus   toxicita   MeSH
• magnetické nanočástice toxicita   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• potkani Wistar MeSH
• synergismus léků MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• kyselina askorbová MeSH
• magnetické nanočástice MeSH

Apelin, the endogenous ligand of the G protein-coupled receptor (APJ), plays an important role in the physiological response to homeostatic perturbations. The aim of the present study was to investigate the effect of apelin on the functions of peritoneal macrophages. A double staining immunofluorescence technique was used to determine the expression of APJ in peritoneal macrophages. Rat peritoneal macrophages were randomly divided into three groups: control, apelin and apelin+F13A. A significant decrease in phagocytic and chemotactic activity of peritoneal macrophages resulted when the macrophages were incubated with [Pry(1)]-Apelin-13 (10 ng/ml). Incubation of peritoneal macrophages with the APJ receptor antagonist, F13A (20 ng/ml) prevented the suppressive effect of apelin on phagocytosis and chemotaxis. Peritoneal macrophages incubated with [Pry(1)]-Apelin-13 exhibited a decrease in the production of TNF-alpha and IL-6 compared to the control macrophages. Incubation of peritoneal macrophages with [Pry(1)]-Apelin-13 plus F13A prevented the decrease in the production of proinflammatory cytokines produced by [Pry(1)]-Apelin-13. In conclusion, apelin may be a mediator that inhibits the functions of activated macrophages.

• MeSH
• apelin farmakologie   MeSH
• fagocytóza účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• mediátory zánětu metabolismus   MeSH
• mezibuněčné signální peptidy a proteiny farmakologie   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• potkani Wistar MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• apelin 13, Pyr(1)- MeSH Prohlížeč
• apelin MeSH
• mediátory zánětu MeSH
• mezibuněčné signální peptidy a proteiny MeSH

The present in vitro experiments demonstrate inhibitory effects of polysubstituted 2-aminopyrimidines on high output production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by interferon-γ and lipopolysaccharide (LPS) in peritoneal macrophages of mouse and rat origin. PGE2 production was inhibited also in LPS-activated human peripheral blood mononuclear cells. A tight dependence of the suppressive activities on chemical structure of pyrimidines was observed. Derivatives containing hydroxyl groups at the C-4 and C-6 positions of pyrimidine ring were devoid of any influence on NO and PGE2. Remarkable inhibitory potential was acquired by the replacement of hydroxyl groups with chlorine, the 4,6-dichloro derivatives being more effective than the monochloro analogues. The effects were further intensified by modification of the amino group at the C-2 position, changing it to the (N,N-dimethylamino)methyleneamino or the formamido ones. There was no substantial difference in the expression of NO-inhibitory effects among derivatives containing distinct types of substituents at the C-5 position (hydrogen, methyl, ethyl, propyl, butyl, phenyl, and benzyl). In contrast to NO, larger substituents then methyl were required to inhibit PGE2 production. Overall, no significant correlation between the extent of NO and PGE2 suppression was observed. The IC50s of derivatives with the strongest effects on both NO and PGE2 were within the range of 2-10 μM. Their NO-inhibitory potential of pyrimidines was stronger than that of non-steroidal anti-inflammatory drugs (NSAIDs) aspirin and indomethacin. The PGE2-inhibitory effectiveness of pyrimidines was about the same as that of aspirin, but weaker as compared to indomethacin. The NO- and PGE2-inhibitory activity of tested pyrimidines has been found associated with decreased expression of iNOS mRNA and COX-2 mRNA, respectively, and with post-translation interactions. Selected NO-/PGE2-inhibitory derivatives decreased severity of intestinal inflammation in murine model of ulcerative colitis.

• Klíčová slova
• Nitric oxide, Prostaglandin E(2), Pyrimidines, Ulcerative colitis,
• MeSH
• antiflogistika nesteroidní aplikace a dávkování   farmakologie   MeSH
• Aspirin farmakologie   MeSH
• cyklooxygenasa 2 genetika   metabolismus   MeSH
• dinoproston antagonisté a inhibitory   biosyntéza   MeSH
• indomethacin farmakologie   MeSH
• interferon gama farmakologie   MeSH
• kolon účinky léků   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• messenger RNA metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• oxid dusnatý antagonisté a inhibitory   biosyntéza   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• potkani inbrední LEW MeSH
• pyrimidiny aplikace a dávkování   farmakologie   MeSH
• synthasa oxidu dusnatého, typ II genetika   metabolismus   MeSH
• ulcerózní kolitida farmakoterapie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• Aspirin MeSH
• cyklooxygenasa 2 MeSH
• dinoproston MeSH
• indomethacin MeSH
• interferon gama MeSH
• lipopolysacharidy MeSH
• messenger RNA MeSH
• mitogenem aktivované proteinkinasy MeSH
• oxid dusnatý MeSH
• pyrimidiny MeSH
• synthasa oxidu dusnatého, typ II MeSH

Our previous research on immunostimulatory properties of trilobolide and its structurally related natural analogues isolated from Laser trilobum (L.) Borkh., encouraged us to investigate structurally related guaianolides belonging to a specific group of sesquiterpene lactones with characteristic glycol moiety attached to the lactone ring. Ever increasing attention has been paid to certain guaianolides such as thapsigargin and trilobolide for their promising anti-inflammatory, anticancer, anti-infectious and SERCA inhibitory activities. However, due to their alkylation capabilities, they might be cytotoxic. Search for compounds with preserved immunobiological properties and decreased cytotoxicity led us to transform some of their structural features, particularly those related to their side chain functionality. For this reason, we prepared a series of over 20 various deacylated, acyl modified, or relactonized derivatives of trilobolide. The immunobiological effects were screened in vitro using the rat peritoneal cells primed with lipopolysaccharide. Secretion of interferon-γ (IFN-γ), interleukins (IL) IL-1β, IL-6 and tumour necrosis factor-α (TNF-α) were determined by ELISA, and nitric oxide (NO) production by Griess reagent. Relation between the molecular structure and immunobiological activity was investigated. Acetylation at 7-OH and 11-OH positions of the lactone ring, or acyl modification of the guaianolide functionalities (including relactonization) of trilobolide, led to inability to stimulate secretion of cytokines and production of NO. Interestingly, minor structural changes achieved by catalytic hydrogenation or hydrogenolysis retained the original immunoactivity of trilobolide. It can be concluded that several new chemically transformed sesquiterpene lactones resembling the immunobiological properties of trilobolide or thapsigargin were prepared and identified. The implication of the lactone vicinal diol (glycol) moiety, combined with other structure functionality, was confirmed as essential for immune properties of the trilobolide or thapsigargin type of guaianolides.

• Klíčová slova
• Cytokines, Guaianolides, Immunoactivity, Nitric oxide, Sesquiterpene lactones, Trilobolide derivatives,
• MeSH
• Apiaceae chemie   MeSH
• butyráty chemie   MeSH
• cytokiny metabolismus   MeSH
• furany chemie   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• laktony chemie   farmakologie   MeSH
• molekulární struktura MeSH
• oxid dusnatý metabolismus   MeSH
• peritoneální makrofágy účinky léků   MeSH
• potkani Wistar MeSH
• seskviterpeny chemie   farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• butyráty MeSH
• cytokiny MeSH
• furany MeSH
• laktony MeSH
• oxid dusnatý MeSH
• seskviterpeny MeSH
• trilobolide MeSH Prohlížeč

A low-molecular-weight (under 10 kDa) dialysable leukocyte extract (called transfer factor, TF) has been shown to be a prospective substance to improve or modulate immune response in autoimmunity, inflammation, infectious diseases or cancers. However, the use of TF has been limited by the absence of any data on the mechanism of its action. Here we show that TF prepared from peripheral blood leukocytes of healthy human donors displays multiple regulatory effects on individual parameters of the immune system. TF decreases proliferation of T and B lymphocytes and partially alters the production of cytokines and nitric oxide by activated macrophages. TF also inhibits production of T helper 1 (Th1) cytokines interleukin 2 (IL-2) and interferon γ, slightly stimulates production of Th2 cytokine IL-10 and considerably enhances the secretion of IL-17 by activated mouse spleen T cells. At the molecular level, TF enhances expression of genes for transcription factor RORγt and for IL-17. The enhanced expression of the RORgt gene corresponds with an increase in the number of RORγt⁺CD4⁺ Th17 cells and with enhanced IL-17 production. In contrast, the expression of the Foxp3 gene and the proportion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells are not significantly changed in the presence of TF. These results suggest that the activation of pro-inflammatory Th17 cells, which have multiple immunoregulatory properties, could be the main mechanism of the immunomodulatory action of a low-molecular-weight leukocyte extract.

• MeSH
• adjuvancia imunologická farmakologie   MeSH
• aktivace lymfocytů účinky léků   MeSH
• B-lymfocyty účinky léků   MeSH
• buněčné dělení účinky léků   MeSH
• CD4-pozitivní T-lymfocyty účinky léků   metabolismus   MeSH
• forkhead transkripční faktory biosyntéza   genetika   MeSH
• interferon gama biosyntéza   genetika   MeSH
• interleukin-17 biosyntéza   genetika   MeSH
• interleukiny biosyntéza   genetika   MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 analýza   biosyntéza   genetika   MeSH
• konkanavalin A farmakologie   MeSH
• kultivované buňky MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• molekulová hmotnost MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• oxid dusnatý biosyntéza   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• podskupiny lymfocytů účinky léků   metabolismus   MeSH
• preklinické hodnocení léčiv MeSH
• regulace genové exprese účinky léků   MeSH
• slezina cytologie   MeSH
• transfer faktor farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• forkhead transkripční faktory MeSH
• Foxp3 protein, mouse MeSH Prohlížeč
• interferon gama MeSH
• interleukin-17 MeSH
• interleukiny MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 MeSH
• konkanavalin A MeSH
• oxid dusnatý MeSH
• transfer faktor MeSH

To test whether macrophages can play any role in hypoxic pulmonary vasoconstriction, we tested the in vitro response of rings from small pulmonary arteries to the activation of macrophages by FMLP, a substance stimulating predominantly membrane-bound NADPH oxidase. A small vessel myograph was used to measure the responses of rings from small pulmonary arteries (300-400 microm) isolated from rat lungs. Rings from 5 rats were placed into both chambers of the myograph. The vessels were stabilized for 40 min and then normalized by automatic stretching to a wall tension equivalent to the intravascular pressure 30 mm Hg. At the start of each experiment, vessels were exposed to 80 mM K+ to obtain maximal contractile response, which was used to normalize subsequent contractile responses. 2x10(6) viable macrophages, obtained by peritoneal lavage, were added into one chamber, then 5 microM FMLP was administrated to both chambers and the tension measurement was started. The hydrogen peroxide concentration produced by stimulated macrophages was measured luminometrically. The concentrations of H2O2 in specimens from chambers containing activated macrophages rose from 3.5+/-1.5 nM to 110+/-28 nM within 25 min of stimulation, while FMLP itself didn't increase the H2O2 concentration from the baseline value (4.5+/-3 nM) in samples from control chambers. After FMLP administration, the tension of the vessel rings in the presence of macrophages reached 0.23+/-0.07 of maximal contractile response, it did not change in controls. The addition of ROS scavenger 4-hydroxy-TEMPO blocked the contractile response to the activation of macrophages. We conclude that the activation of macrophages stimulates the contraction of small pulmonary arteries and that this contraction is probably mediated by reactive oxygen species.

• MeSH
• arteria pulmonalis metabolismus   MeSH
• krysa rodu Rattus MeSH
• orgánové kultury - kultivační techniky MeSH
• peritoneální makrofágy metabolismus   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• vazokonstrikce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• reaktivní formy kyslíku MeSH

Two major effector systems are frequently implicated in the immune and endothelial cell alternations associated with inflammation. They include the enhanced production of reactive oxygen species and diminished bioavailability of nitric oxide (NO). Importantly, these processes can be regulated by endogenously produced methylarginines, inhibitors for NO derived from macrophages and endothelial cells. Therefore, the aim of this study was to show the potential pharmacological intervention of methylarginines (N(G)-methyl-L-arginine, L-NMMA; N(G), N(G)'-dimethyl-L-arginine-symmetric dimethylarginine, SDMA; and N(G), N(G)-dimethyl-L-arginine-asymmetric dimethylarginine, ADMA) in activation of murine peritoneal (RAW 264.7) and alveolar (MHS) macrophages with lipopolysaccharide from Gram-negative bacteria (LPS). The data presented in this study clearly declare that L-NMMA (1-50μM) and ADMA (10-50 μM) significantly inhibited the LPS-induced NO production from macrophages in a concentration-dependent manner. It was demonstrated, for the first time, that the ADMA- and L-NMMA-induced down regulation of NO production was accompanied by reduced expression of mRNA and protein for inducible NO synthase as well as decreased activation of nuclear factor-κB. Importantly, we found a negative correlation between the ADMA-dependent reduction of NO production and ADMA-increased superoxide formation, which indicates that ADMA can negatively affect the balance in LPS-induced macrophage-derived production of reactive mediators. The only effect of SDMA was observed for LPS-triggered superoxide production, which was significantly decreased in its highest concentration (50 μM). In summary, L-NMMA and ADMA can mediate their effects on macrophage activation via regulation of intracellular signaling pathways, which can affect critical functions in activated macrophages.

• MeSH
• alveolární makrofágy účinky léků   imunologie   metabolismus   MeSH
• arginin analogy a deriváty   chemie   farmakologie   MeSH
• buněčné kultury MeSH
• buněčné linie MeSH
• exprese genu účinky léků   MeSH
• lipopolysacharidy toxicita   MeSH
• myši MeSH
• NF-kappa B antagonisté a inhibitory   biosyntéza   genetika   MeSH
• oxid dusnatý biosyntéza   MeSH
• peritoneální makrofágy účinky léků   imunologie   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• superoxidy metabolismus   MeSH
• synthasa oxidu dusnatého, typ II antagonisté a inhibitory   biosyntéza   genetika   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• dimethylarginine MeSH Prohlížeč
• lipopolysaccharide, E. coli O26-B6 MeSH Prohlížeč
• lipopolysacharidy MeSH
• NF-kappa B MeSH
• Nos2 protein, mouse MeSH Prohlížeč
• oxid dusnatý MeSH
• superoxidy MeSH
• synthasa oxidu dusnatého, typ II MeSH