Bilirubin has potent biological beneficial effects, protecting against atherosclerosis, obesity, and metabolic syndrome. The aim of this study was to assess serum bilirubin concentrations and (TA)n and (GT)n microsatellite variations in the promoter regions of the UGT1A1 and HMOX1 genes, respectively, in patients with type 2 diabetes mellitus (T2DM). The study was carried out in 220 patients with T2DM and 231 healthy control subjects, in whom standard biochemical tests were performed. The (TA)n and (GT)n dinucleotide variations were determined by means of fragment (size-based) analysis using an automated capillary DNA sequencer. Compared to controls, both male and female patients with T2DM had lower serum bilirubin concentrations (9.9 vs. 12.9 μmol/L, and 9.0 vs. 10.6 μmol/L, in men and women, respectively, p < 0.001). Phenotypic Gilbert syndrome was much less prevalent in T2DM patients, as was the frequency of the (TA)7/7UGT1A1 genotype in male T2DM patients. (GT)nHMOX1 genetic variations did not differ between diabetic patients and controls. Our results demonstrate that the manifestation of T2DM is associated with lower serum bilirubin concentrations. Consumption of bilirubin due to increased oxidative stress associated with T2DM seems to be the main explanation, although (TA)n repeat variations in UGT1A1 partially contribute to this phenomenon.

• Klíčová slova
• Gilbert syndrome, HMOX1, UGT1A1, benign hyperbilirubinemia, bilirubin, heme oxygenase, type 2 diabetes mellitus,
• MeSH
• bilirubin metabolismus   MeSH
• diabetes mellitus 2. typu * genetika   MeSH
• genotyp MeSH
• glukuronosyltransferasa genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• promotorové oblasti (genetika) MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• bilirubin MeSH
• glukuronosyltransferasa MeSH
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč

Background The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03. Conclusions Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03033810.

• Klíčová slova
• coronary flow reserve, fractional flow reserve, instantaneous wave‐free ratio,
• MeSH
• frakční průtoková rezerva myokardu * MeSH
• hemodynamika MeSH
• hemoglobiny MeSH
• hemoxygenasa-1 genetika   MeSH
• koronární angiografie metody   MeSH
• koronární stenóza * MeSH
• lidé MeSH
• renální insuficience * MeSH
• synthasa oxidu dusnatého, typ III MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hemoglobiny MeSH
• hemoxygenasa-1 MeSH
• synthasa oxidu dusnatého, typ III MeSH

The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondrial function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex II/III, reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.

• MeSH
• edaravon farmakologie   MeSH
• encefalomyelitida autoimunitní experimentální * patologie   MeSH
• encefalomyelitida * MeSH
• exprese genu MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• myši MeSH
• stupeň závažnosti nemoci MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• edaravon MeSH
• faktor 2 související s NF-E2 MeSH
• hemoxygenasa-1 MeSH

Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes. In contrast to G-CSF, CoPP does not increase the number of circulating T cells. Transplantation of CoPP-mobilized peripheral blood mononuclear cells (PBMC) results in higher chimerism and faster hematopoietic reconstitution than transplantation of PBMC mobilized by G-CSF. Although CoPP is used to activate Nrf2/HO-1 axis, the observed effects are Nrf2/HO-1 independent. Concluding, CoPP increases expression of mobilization-related cytokines and has superior mobilizing efficiency compared with recombinant G-CSF. This observation could lead to the development of new strategies for the treatment of neutropenia and HSPC transplantation.

• Klíčová slova
• CoPP, HO-1, granulocyte colony-stimulating factor, hematopoietic stem and progenitor cells, mobilization,
• MeSH
• faktor stimulující kolonie granulocytů metabolismus   MeSH
• granulocyty účinky léků   MeSH
• hematopoetické kmenové buňky účinky léků   MeSH
• hemoxygenasa-1 nedostatek   genetika   MeSH
• mobilizace hematopoetických kmenových buněk MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• protoporfyriny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cobaltiprotoporphyrin MeSH Prohlížeč
• faktor stimulující kolonie granulocytů MeSH
• hemoxygenasa-1 MeSH
• protoporfyriny MeSH

Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.o., 9 weeks)-treated groups. After 2 weeks of treatment, rats were subjected to 30-min left coronary artery occlusion or sham operation. Systolic blood pressure (SBP) and echocardiography (ECHO) measurements were performed at the beginning of study, 4 days before, and 7 weeks after MI. At the end of the study, tissue samples were collected for histological and biochemical analyses. We demonstrated that EET-B treatment did not affect blood pressure and cardiac parameters in SHR prior to MI. Fractional shortening (FS) was decreased to 18.4 ± 1.0% in vehicle-treated MI rats compared with corresponding sham (30.6 ± 1.0%) 7 weeks following MI induction. In infarcted SHR hearts, EET-B treatment improved FS (23.7 ± 0.7%), markedly increased heme oxygenase-1 (HO-1) immunopositivity in cardiomyocytes and reduced cardiac inflammation and fibrosis (by 13 and 19%, respectively). In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI.

• Klíčová slova
• blood pressure, epoxyeicosatrienoic acid, heart failure, myocardial infarction, spontaneously hypertensive rat,
• MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• infarkt myokardu farmakoterapie   genetika   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• kyseliny arachidonové aplikace a dávkování   chemie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední SHR MeSH
• srdce patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• hemoxygenasa-1 MeSH
• kyseliny arachidonové MeSH

Bilirubin is considered to be one of the most potent endogenous antioxidants in humans. Its serum concentrations are predominantly affected by the activity of hepatic bilirubin UDP-glucuronosyl transferase (UGT1A1). Our objective was to analyze the potential bilirubin-modulating effects of natural polyphenols from milk thistle (Silybum marianum), a hepatoprotective herb. Human hepatoblastoma HepG2 cells were exposed to major polyphenolic compounds isolated from milk thistle. Based on in vitro studies, 2,3-dehydrosilybins A and B were selected as the most efficient compounds and applied either intraperitoneally or orally for seven days to C57BL/6 mice. After, UGT1A1 mRNA expression, serum, intrahepatic bilirubin concentrations, and lipoperoxidation in the liver tissue were analyzed. All natural polyphenols used increased intracellular concentration of bilirubin in HepG2 cells to a similar extent as atazanavir, a known bilirubinemia-enhancing agent. Intraperitoneal application of 2,3-dehydrosilybins A and B (the most efficient flavonoids from in vitro studies) to mice (50 mg/kg) led to a significant downregulation of UGT1A1 mRNA expression (46 ± 3% of controls, p < 0.005) in the liver and also to a significant increase of the intracellular bilirubin concentration (0.98 ± 0.03vs.1.21 ± 0.02 nmol/mg, p < 0.05). Simultaneously, a significant decrease of lipoperoxidation (61 ± 2% of controls, p < 0.005) was detected in the liver tissue of treated animals, and similar results were also observed after oral treatment. Importantly, both application routes also led to a significant elevation of serum bilirubin concentrations (125 ± 3% and 160 ± 22% of the controls after intraperitoneal and oral administration, respectively, p < 0.005 in both cases). In conclusion, polyphenolic compounds contained in silymarin, in particular 2,3-dehydrosilybins A and B, affect hepatic and serum bilirubin concentrations, as well as lipoperoxidation in the liver. This phenomenon might contribute to the hepatoprotective effects of silymarin.

• MeSH
• bilirubin metabolismus   MeSH
• buňky Hep G2 MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• glukuronosyltransferasa genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• intracelulární prostor metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši inbrední C57BL MeSH
• peroxidace lipidů účinky léků   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• silibinin aplikace a dávkování   farmakologie   MeSH
• silymarin izolace a purifikace   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bilirubin MeSH
• flavonoidy MeSH
• glukuronosyltransferasa MeSH
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• silibinin MeSH
• silymarin MeSH
• UGT1A1 enzyme MeSH Prohlížeč

Oxidative stress and inflammation are predominant features of several chronic diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a major arbiter in counteracting these insults via up-regulation of several defensive proteins, including heme oxygenase-1 (HO-1). HO-1-derived carbon monoxide (CO) exhibits anti-inflammatory actions and can be delivered to tissues by CO-releasing agents. In this study we assessed the pharmacological and anti-inflammatory properties of HYCO-3, a dual activity compound obtained by conjugating analogues of the CO-releasing molecule CORM-401 and dimethyl fumarate (DMF), an immunomodulatory drug known to activate Nrf2. HYCO-3 induced Nrf2-dependent genes and delivered CO to cells in vitro and tissues in vivo, confirming that the two expected pharmacological properties of this agent are achieved. In mice challenged with lipopolysaccharide, orally administered HYCO-3 reduced the mRNA levels of pro-inflammatory markers (TNF-α, IL-1β and IL-6) while increasing the expression of the anti-inflammatory genes ARG1 and IL-10 in brain, liver, lung and heart. In contrast, DMF or CORM-401 alone or their combination decreased the expression of pro-inflammatory genes but had limited influence on anti-inflammatory markers. Furthermore, HYCO-3 diminished TNF-α and IL-1β in brain and liver but not in lung and heart of Nrf2-/- mice, indicating that the CO-releasing part of this hybrid contributes to reduction of pro-inflammation and that this effect is organ-specific. These data demonstrate that the dual activity of HYCO-3 results in enhanced efficacy compared to the parent compounds indicating the potential exploitation of hybrid compounds in the development of effective anti-inflammatory therapies.

• Klíčová slova
• Carbon monoxide (CO), Dual-activity molecules, Inflammation, Macrophage phenotype, Nrf2 activators,
• MeSH
• antiflogistika farmakologie   MeSH
• antioxidancia metabolismus   MeSH
• cytokiny genetika   metabolismus   MeSH
• exprese genu MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• kultivované buňky MeSH
• lipopolysacharidy škodlivé účinky   MeSH
• makrofágy účinky léků   imunologie   metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• mikroglie účinky léků   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• oxid uhelnatý metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• zánět farmakoterapie   etiologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika MeSH
• antioxidancia MeSH
• cytokiny MeSH
• faktor 2 související s NF-E2 MeSH
• hemoxygenasa-1 MeSH
• lipopolysacharidy MeSH
• mediátory zánětu MeSH
• oxid uhelnatý MeSH

The aim of our study was to assess the possible relationships among heme oxygenase (HMOX), bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations, serum bilirubin levels, and Fabry disease (FD). The study included 56 patients with FD (M : F ratio = 0.65) and 185 healthy individuals. Complete standard laboratory and clinical work-up was performed on all subjects, together with the determination of total peroxyl radical-scavenging capacity. The (GT)n and (TA)n dinucleotide variations in the HMOX1 and UGT1A1 gene promoters, respectively, were determined by DNA fragment analysis. Compared to controls, patients with FD had substantially lower serum bilirubin levels (12.0 versus 8.85 μmol/L, p = 0.003) and also total antioxidant capacity (p < 0.05), which showed a close positive relationship with serum bilirubin levels (p = 0.067) and the use of enzyme replacement therapy (p = 0.036). There was no association between HMOX1 gene promoter polymorphism and manifestation of FD. However, the presence of the TA7 allele UGT1A1 gene promoter, responsible for higher systemic bilirubin levels, was associated with a twofold lower risk of manifestation of FD (OR = 0.51, 95% CI = 0.27-0.97, p = 0.038). Markedly lower serum bilirubin levels in FD patients seem to be due to bilirubin consumption during increased oxidative stress, although UGT1A1 promoter gene polymorphism may modify the manifestation of FD as well.

• MeSH
• antioxidancia metabolismus   MeSH
• bilirubin krev   MeSH
• dospělí MeSH
• Fabryho nemoc krev   enzymologie   genetika   MeSH
• glukuronosyltransferasa genetika   MeSH
• hemoxygenasa-1 genetika   MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• promotorové oblasti (genetika) MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• bilirubin MeSH
• glukuronosyltransferasa MeSH
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč
• UGT1A1 enzyme MeSH Prohlížeč

Silybum marianum (milk thistle) is a medicinal plant used for the treatment of various liver disorders. This study examined whether the main flavonolignans from S. marianum (i.e. silybin, silychristin, silydianin) and their 2,3-dehydro derivatives (i.e. 2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin) activate the Nrf2 pathway, which regulates the expression of genes encoding many cytoprotective enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1). After 48h of exposure, 2,3-dehydrosilydianin at concentrations of 25μM and higher significantly elevated the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. In contrast, other tested compounds at non-cytotoxic concentrations had a mild or negligible effect on the NQO1 activity. Using a luciferase reporter assay, 2,3-dehydrosilydianin was found to significantly activate transcription via the antioxidant response element in stably transfected human AREc32 reporter cells. Moreover, 2,3-dehydrosilydianin caused the accumulation of Nrf2 and significantly induced the expression of the Nqo1 gene at both the mRNA and protein levels in Hepa1c1c7 cells. We found that 2,3-dehydrosilydianin also increased to some extent the expression of other Nrf2 target genes, namely of the heme oxygenase-1 gene (Hmox1) and the glutamate-cysteine ligase modifier subunit gene (Gclm). We conclude that 2,3-dehydrosilydianin activates Nrf2 and induces Nrf2-mediated gene expression in Hepa1c1c7 cells.

• Klíčová slova
• Flavonolignans, NQO1, Nrf2, Silybin, Silybum marianum, Silymarin,
• MeSH
• exprese genu účinky léků   MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• glutamátcysteinligasa genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• molekulární struktura MeSH
• myši MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• ostropestřec mariánský chemie   MeSH
• silibinin MeSH
• silymarin farmakologie   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 MeSH
• GCLM protein, mouse MeSH Prohlížeč
• glutamátcysteinligasa MeSH
• hemoxygenasa-1 MeSH
• Hmox1 protein, mouse MeSH Prohlížeč
• membránové proteiny MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• Nqo1 protein, mouse MeSH Prohlížeč
• silibinin MeSH
• silidianin MeSH Prohlížeč
• silychristin MeSH Prohlížeč
• silymarin MeSH

AIMS: Heme oxygenase-1 (HO-1; HMOX1 in human, Hmox1 in mice) is an antioxidative enzyme affecting wide range of sub-cellular processes. It was shown to modulate tumor growth or vascular-related diseases, thus being putative molecular target for tailored therapies. Therefore it is of importance to elucidate novel compounds regulating HO-1 activity/expression and to delineate mechanisms of their action. In the present study we aimed to understand mode of action of valproic acid (VA), an antiepileptic drug, on HO-1 expression. RESULTS: We demonstrated that HO-1 expression is decreased by VA at protein but not mRNA level in human alveolar rhabdomyosarcoma cell line CW9019. Nrf2 transcription factor, the activator of HO-1 expression through ARE sequence, was excluded as a mediator of HO-1 decrease, as VA downregulated Bach1, a Nrf2 repressor, concomitantly upregulating ARE activation. Also miRNA-dependent inhibition was excluded as a mechanism of HMOX1 regulation. However, co-immunoprecipitation assay showed a higher level of ubiquitinated HO-1 after VA treatment. Accordingly, MG132, an inhibitor of proteasomal degradation, reversed the effect of VA on HO-1 suggesting that decrease in HO-1 expression by VA is through protein stability. The inhibitory effect of VA on HO-1 was also observed in murine cells including embryonic fibroblasts isolated from Nrf2-deficient mice, what confirms Nrf2-independent effect of the compound. Importantly, VA decreased also HO-1 expression and activity in murine skeletal muscles in vivo. CONCLUSION: Our data indicate that VA downregulates HO-1 by acting through ubiquitin-proteasomal pathway leading to decrease in protein level.

• Klíčová slova
• Heme Oxygenase-1, Nrf2, Rhabdomyosarcoma, Ubiquitination, Valproic acid,
• MeSH
• antikonvulziva farmakologie   MeSH
• buněčné linie MeSH
• down regulace účinky léků   MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• inhibitory enzymů farmakologie   MeSH
• kyselina valproová farmakologie   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• proteolýza účinky léků   MeSH
• ubikvitinace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH
• faktor 2 související s NF-E2 MeSH
• hemoxygenasa-1 MeSH
• inhibitory enzymů MeSH
• kyselina valproová MeSH
• Nfe2l2 protein, mouse MeSH Prohlížeč
• proteasomový endopeptidasový komplex MeSH