Jaterní enzymy (jaterní testy) jsou v běžné populaci důležitými markéry jaterních nemocí včetně jaterní steatózy asociované s metabolickou dysfunkcí (metabolic dysfunction-associated steatotic liver disease, MASLD), ale současně i významnými prediktory kardiovaskulární i celkové morbidity a mortality. Prevalence elevace jaterních enzymů je (nejen) v České populaci velmi vysoká a jejich rizikový potenciál bývá bagatelizován. Je velice žádoucí snižovat aktivity jaterních enzymů - režimovými opatřeními i farmakoterapií.
Liver enzymes (liver function tests) in the general population are important markers of liver disease, including MASLD (metabolic dysfunction-associated static liver disease), but also important predictors of cardiovascular and overall morbidity and mortality. The prevalence of liver enzyme elevations is very high (not only) in the Czech population and their risk potential is often underestimated. It is highly desirable to reduce the activity of liver enzymes - by regimen measures and pharmacotherapy.
BACKGROUND: Although regular physical activity improves immune competency and reduces the prevalence of inflammatory diseases, strenuous training in elite athletes is associated with an increased susceptibility to infectious complications. Therefore, the objective of our study was to assess the routinely examined parameters of the complement system in elite athletes. The study was carried out in a cohort of elite athletes (n = 134) and healthy control subjects (n = 110). In all subjects, besides a routine laboratory check-up, serum concentrations of the C3 and C4 complement components, mannose-binding lectin (MBL), as well as activation of all three complement pathways were determined. RESULTS: Compared to healthy controls, lower C3 and C4 complement component concentrations were observed in elite athletes (0.96 ± 0.1 vs. 1.08 ± 0.2 mg/L, and 0.18 ± 0.1 vs. 0.25 ± 0.1 mg/L, respectively, p < 0.05); with much higher frequency rates of C3 and C4 deficiencies in athletes (31.3 vs. 14.5%, and 6 vs. 0%, p < 0.05). Simultaneously, athletes had much higher frequency rates of deficiencies of activation of classical and alternative complement pathways; while, deficiency of activation of the lectin pathway was similar in both cohorts. CONCLUSIONS: We confirmed a high frequency of defects in the complement system in elite athletes. Lower concentrations of C3 and C4 complement components, with high frequencies of deficiencies of the classical and alternative complement activation pathways were the most prevalent disorder of the complement system in elite athletes. Further studies are needed to uncover the functional impacts of these observations upon the susceptibility to infectious diseases.
- Publikační typ
- časopisecké články MeSH
Gilbert's syndrome, also known as benign hyperbilirubinaemia, was described more than 100 years ago. It has usually been considered a physiological abnormality characterised by a mild elevation of the systemic level of unconjugated bilirubin, in the absence of any underlying liver or overt haemolytic disease. However, since the re-discovery of the potent antioxidant effects of bilirubin in the late 1980s, as well as multiple intracellular signalling pathways affected by bilirubin, an ever-increasing body of evidence suggests that individuals with Gilbert's syndrome may benefit from the mild hyperbilirubinaemia and are actually protected from the development of a wide variety of "diseases of civilisation" such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases. This review analyses the current state of medical knowledge given recent discoveries in this rapidly developing field, as well as their possible clinical significance, and provides a new perspective on this condition.
- MeSH
- antioxidancia MeSH
- bilirubin metabolismus MeSH
- Gilbertova nemoc * metabolismus MeSH
- hyperbilirubinemie metabolismus MeSH
- játra metabolismus MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Bilirubin has several physiological functions, both beneficial and harmful. In addition to reactive oxygen species-scavenging activities, bilirubin has potent immunosuppressive effects associated with long-term pathophysiological sequelae. It has been recently recognized as a hormone with endocrine actions and interconnected effects on various cellular signaling pathways. Current studies show that bilirubin also decreases adiposity and prevents metabolic and cardiovascular diseases. All in all, the physiological importance of bilirubin is only now coming to light, and strategies for increasing plasma bilirubin levels to combat chronic diseases are starting to be considered. This review discusses the beneficial effects of increasing plasma bilirubin, incorporates emerging areas of bilirubin biology, and provides key concepts to advance the field.
- MeSH
- bilirubin * metabolismus farmakologie MeSH
- hemoxygenasa-1 metabolismus MeSH
- kardiovaskulární nemoci * MeSH
- lidé MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Oxidative stress and inflammation contribute significantly to atherogenesis. We and others have demonstrated that mildly elevated serum bilirubin levels protect against coronary and peripheral atherosclerosis, most likely due to the antioxidant and anti-inflammatory activities of bilirubin. The aim of the present study was to assess serum bilirubin and the markers of oxidative stress and inflammation in both healthy subjects and patients with various forms of atherosclerosis. The study was performed in patients with premature myocardial infarction (n = 129), chronic ischemic heart disease (n = 43), peripheral artery disease (PAD, n = 69), and healthy subjects (n = 225). In all subjects, standard serum biochemistry, UGT1A1 genotypes, total antioxidant status (TAS), and concentrations of various pro- and anti-inflammatory chemokines were determined. Compared to controls, all atherosclerotic groups had significantly lower serum bilirubin and TAS, while having much higher serum high-sensitivity C-reactive protein (hsCRP) and most of the analyzed proinflammatory cytokines (p < 0.05 for all comparisons). Surprisingly, the highest inflammation, and the lowest antioxidant status, together with the lowest serum bilirubin, was observed in PAD patients, and not in premature atherosclerosis. In conclusion, elevated serum bilirubin is positively correlated with TAS, and negatively related to inflammatory markers. Compared to healthy subjects, patients with atherosclerosis have a much higher degree of oxidative stress and inflammation.
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Fototerapie je standardním léčebným postupem u zavážné novorozenecké žloutenky. Tato léčba však může být doprovázena závažnými zdravotními dopady, které zahrnují zvýšení celkové mortality, zvýšený výskyt některých nádorových onemocnění, diabetu mellitu 1. typu, obzvláště u novorozenců s velmi nízkou porodní hmotností. I přes široké používání fototerapie v klinické neonatologii je velmi málo známo o biologických účincích oxidačních produktů bilirubinu, které vznikají během fototerapie novorozenecké žloutenky, a zcela chybí studie, které by se systematicky zabývaly celým procesem fotooxidace bilirubinu. Všechny tyto aspekty přitom mohou vysvětlit pozorované nežádoucí účinky fototerapie. Cílem předkládaného projektu je tedy systematické studium procesu fotooxidace bilirubinu za použití interdisciplinárního přístupu, který kombinuje biologické a chemické vědní obory.; Phototherapy is a golden standard treatment of severe neonatal jaundice. However, this treatment modality might be associated with significant health issues including increased overall mortality, increased risk of certain cancers or type 1 diabetes mellitus, especially in very low weight birth neonates. Despite a widespread use of phototherapy in clinical neonatology, only little is known about bilirubin oxidation products generated during phototherapy, and almost no studies have been performed to systematically explore the whole process of bilirubin photooxidation. All these aspects may account for observed clinical side effects. Thus, these issues are the main aim of the current project which combines interdisciplinary approach between life and basic sciences.
- MeSH
- bilirubin chemie metabolismus škodlivé účinky účinky záření MeSH
- fototerapie škodlivé účinky MeSH
- hemoxygenasa-1 MeSH
- novorozenec MeSH
- novorozenecká žloutenka terapie MeSH
- oxid uhelnatý MeSH
- oxidace-redukce účinky záření MeSH
- rizikové faktory MeSH
- Check Tag
- novorozenec MeSH
- Konspekt
- Pediatrie
- NLK Obory
- biochemie
- perinatologie a neonatologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Bilirubin is a tetrapyrrolic compound originating from heme catabolism. Although originally considered only a potentially dangerous waste product, it has become increasingly evident that this molecule represents an important modulator of various biological functions in the human body. Bilirubin appears to have versatile functions, from cell signaling (behaving almost like a "real" hormonal substance), modulation of metabolism, to immune regulation, affecting biological activities with apparent clinical and even therapeutic consequences. These activities may be the reason for the lower incidence of diseases of civilisation (cardiovascular diseases, arterial hypertension, diabetes, obesity, metabolic syndrome, certain cancers, autoimmune, and neurodegenerative diseases) observed in individuals with a chronic mild unconjugated hyperbilirubinemia, a typical sign of Gilbert's syndrome. While higher serum concentrations of unconjugated bilirubin may serve as an important protective factor against these diseases, low levels of bilirubin are associated with the opposite effect.
- MeSH
- barva MeSH
- bilirubin analýza klasifikace MeSH
- hem metabolismus MeSH
- hyperbilirubinemie klasifikace patofyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Significance: As the central metabolic organ, the liver is exposed to a variety of potentially cytotoxic, proinflammatory, profibrotic, and carcinogenic stimuli. To protect the organism from these deleterious effects, the liver has evolved a number of defense systems, which include antioxidant substrates and enzymes, anti-inflammatory tools, enzymatic biotransformation systems, and metabolic pathways. Recent Advances: One of the pivotal systems that evolved during phylogenesis was the heme catabolic pathway. Comprising the important enzymes heme oxygenase and biliverdin reductase, this complex pathway has a number of key functions including enzymatic activities, but also cell signaling, and DNA transcription. It further generates two important bile pigments, biliverdin and bilirubin, as well as the gaseous molecule carbon monoxide. These heme degradation products have potent antioxidant, immunosuppressive, and cytoprotective effects. Recent data suggest that the pathway participates in the regulation of metabolic and hormonal processes implicated in the pathogenesis of hepatic and other diseases. Critical Issues: This review discusses the impact of the heme catabolic pathway on major liver diseases, with particular focus on the involvement of cellular targeting and signaling in the pathogenesis of these conditions. Future Directions: To utilize the biological consequences of the heme catabolic pathway, several unique therapeutic strategies have been developed. Research indicates that pharmaceutical, nutraceutical, and lifestyle modifications positively affect the pathway, delivering potentially long-term clinical benefits. However, further well-designed studies are needed to confirm the clinical benefits of these approaches. Antioxid. Redox Signal. 35, 734-752.
- MeSH
- biliverdin metabolismus MeSH
- hem * metabolismus MeSH
- hemová oxygenasa (decyklizující) metabolismus MeSH
- hemoxygenasa-1 metabolismus MeSH
- lidé MeSH
- nemoci jater * MeSH
- oxid uhelnatý metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Bilirubin je hlavním produktem katabolické dráhy hemu a jeho sérové koncentrace jsou v negativním vztahu k riziku chorob způsobených oxidačním stresem, jako jsou kardiovaskulární, nádorová, autoimunitní a neurodegenerativní nemoci. Příznivý účinek mírně zvýšených hladin bilirubinu se projevuje již s každým mikromolárním zvýšením jeho koncentrace v krevním séru. Hlavní enzymy katabolické dráhy hemu, hemoxygenáza (HMOX) a bilirubin UDP-glukuronosyltransferáza (UGT1A1), jsou ovlivnitelné mnoha xenobiotiky. Hlavním cílem tohoto výzkumného projektu je modulace obou enzymů (nejlépe indukcí HMOX1 a současnou mírnou inhibicí UGT1A) nutraceutiky s cílem mírně zvýšit systémovou koncentraci bilirubinu. Z publikovaných dat vyplývá, že flavonolignany obsažené v silymarinovém komplexu by mohly splňovat tyto předpoklady. V tomto projektu zhodnotíme možnou schopnost čistých jednotlivých látek silymarinového komplexu modulovat tyto enzymy a ovlivnit tak systémové koncentrace bilirubinu.; Bilirubin is the major product of the heme catabolic pathway and its serum concentrations are in negative relationship with the risk of oxidative stress-mediated disorders, such as cardiovascular, cancer, autoimmune and neurodegenerative diseases. The beneficial effects of mildly elevated serum bilirubin levels are detectable with even each micromolar increase of its serum concentrations. The major enzymes in the heme catabolic pathway, heme oxygenase (HMOX) and bilirubin UDP-glucuronosyl transferase (UGT1A1), are modifiable by a number of xenobiotics. Thus, the major aim of the current research project is to nutritionally modulate both enzymes (at the best by HMOX1 induction and simultaneous partial UGT1A1 inhibition) to mildly increase systemic bilirubin concentrations. Based on the published data, flavonolignans from the silymarin complex might fulfill these prerequisites. We will evaluate whether individual pure components of silymarin complex are able to modulate the enzymes involved in bilirubin metabolism to affect systemic concentrations of bilirubin.
- MeSH
- bilirubin MeSH
- flavonolignany terapeutické užití MeSH
- glukuronosyltransferasa MeSH
- hemoxygenasa-1 MeSH
- hyperbilirubinemie chemicky indukované MeSH
- lidé MeSH
- oxidační stres MeSH
- potravní doplňky MeSH
- primární prevence MeSH
- rostlinné přípravky MeSH
- silymarin terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- preventivní medicína
- vnitřní lékařství
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
