- MeSH
- bilirubin * izolace a purifikace krev metabolismus MeSH
- biopsie metody MeSH
- choláty izolace a purifikace metabolismus škodlivé účinky MeSH
- cholestáza * klasifikace patofyziologie patologie MeSH
- diagnostické techniky gastrointestinální klasifikace trendy MeSH
- diagnostické techniky molekulární metody trendy MeSH
- histologické techniky metody trendy MeSH
- hyperbilirubinemie komplikace patofyziologie patologie MeSH
- imunohistochemie metody MeSH
- játra anatomie a histologie patofyziologie patologie MeSH
- klinické laboratorní techniky metody trendy MeSH
- laboratorní medicína metody MeSH
- lidé MeSH
- mezioborová komunikace MeSH
- statistika jako téma MeSH
- žluč * fyziologie metabolismus MeSH
- žlučové kyseliny a soli izolace a purifikace metabolismus škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Mild constitutive hyperbilirubinemia is associated with a reduced risk of cardiovascular diseases, diabetes, and cancer. Since these pathologies are associated with aging, inflammation, and oxidative stress, we investigated whether hyperbilirubinemia interferes with ROS homeostasis in cell cultures and with inflammation, senescence, and mitochondrial dysfunction in aged rats. Human embryonic kidney cells and rat primary fibroblasts showed a dose-dependent decrease in the ratio of oxidized/reduced glutathione, intracellular H2O2 levels, and mitochondrial ROS production, with increasing bilirubin concentrations in the culture media. Compared to their normobilirubinemic siblings, aged hyperbilirubinemic Gunn rats showed significantly smaller amounts of visceral fat, better glucose tolerance, and decreased serum levels of proinflammatory cytokines TNFα, IL-1β, and IL-18. Simultaneously, livers from Gunn rats showed decreased expression of senescence markers and cell cycle inhibitors p21 and p16. Mitochondria from aged Gunn rats showed higher respiration and lower H2O2 production compared to controls. In conclusion, we demonstrated that mildly elevated serum bilirubin is generally associated with attenuation of oxidative stress and with better anthropometric parameters, decreased inflammatory status, increased glucose tolerance, fewer signs of cellular senescence, and enhanced mitochondrial function in aged rats.
- MeSH
- bilirubin krev MeSH
- fibroblasty metabolismus patologie MeSH
- hyperbilirubinemie krev patologie MeSH
- intracelulární prostor metabolismus MeSH
- kultivované buňky MeSH
- metabolické nemoci komplikace patologie MeSH
- mitochondrie metabolismus MeSH
- potkani Gunn MeSH
- reaktivní formy kyslíku metabolismus MeSH
- stárnutí patologie MeSH
- zánět komplikace patologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact.
- MeSH
- artritida experimentální krev patologie MeSH
- bilirubin krev MeSH
- biologické markery krev MeSH
- hyperbilirubinemie krev patologie MeSH
- krysa rodu rattus MeSH
- potkani inbrední LEW MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Gilbertův syndrom (GS) je definován jako geneticky podmíněné onemocnění charakterizované mírnou chronickou nekonjugovanou hyperbilirubinémií bez přítomnosti jaterního onemocnění či zjevné hemolýzy. Jeho podstatou je mutace specifické uridindifosfát glukuronosyltransferázy katalyzující glukuronidaci nekonjugovaného bilirubinu, která má za následek snížení aktivity enzymu. Klinicky jde o benigní syndrom nevyžadující žádnou terapeutickou intervenci. Tím důležitější je ovšem jeho správná diagnostika a odlišení od závažných onemocnění jaterního parenchymu. V poslední době je předmětem intenzivního výzkumu především antioxidační úloha bilirubinu a vztah GS k rozvoji aterosklerózy koronárních i periferních cév a onemocnění podmíněných oxidačním stresem, zejména ischemické choroby srdeční. Diskutován je též vztah GS k hemolýze, novorozenecké žloutence, pigmentové cholelitiáze, schizofrenii a interakcím s některými léčivy.
Gilbert's syndrome is defined as a hereditary, mild, chronic, unconjugated hyperbilirubinemia occurring in the absence of overt hemolysis or any other evidence of liver disease. It is caused by a mutation of the specific UDP glucuronosyl transferase conjugating bilirubin with glucuronic acid resulting in a reduced activity of this enzyme. Gilbert's syndrome is considered as a rather benign disorder without necessity of any therapeutic intervention. It is therefore crucial to establish a correct diagnosis and differentiate this syndrome from serious disorders of the liver tissue. In recent years strong antioxidant effects of bilirubinwere demonstrated in numerous studies and the protective role of hyperbilirubinemia in the pathogenesis of various oxidative stress-mediated diseases was suggested. Gilbert's syndrome and its relationship to associated disorders such as hemolysis, pigment cholelithiasis, neonatal jaundice, schizophrenia and drug interactions are also being discussed.
The aim of the study was to identify moderate liver impairment in a group of hyperbilirubinaemic adolescents. Using gas chromatography we assessed both total bile acid and primary bile acid levels in 50 adolescents with juvenile hyperbilirubinaemia. At the same time we performed hepatologic examinations and subsequent follow-up assessment of these patients for a period of at least 2 years. As a control group we examined 30 adolescents without any impairment of both the liver and gastrointestinal tract, and 18 patients with low grade (moderately) active chronic hepatitis. In both groups we assessed total and primary bile acids levels as well as conventional liver tests (bilirubin, ALT, AST). On the basis of the clinical course and laboratory findings we divided our patients with juvenile hyperbilirubinaemia into two groups: a group of individuals with Gilbert’s syndrome (30 patients) and a group of individuals with probable moderate liver impairment (20 patients). The latter group consisted of the adolescents who exhibited bilirubinaemia over 90 μmol/l and/or exhibited hepatomegaly or splenomegaly proved by the ultrasound examination and/or exhibited intermittent elevation of the liver aminotransferases serum levels. In the group of individuals with moderate liver impairment serum total bile acid levels were significantly elevated in 26% of patients, and the serum cholic acid level was significantly elevated in 25% of patients. These two parameters mutually correlated at a high level of significance. Juvenile hyperbilirubinaemia is one of the common conditions of adolescent age. Its etiology is diverse; it includes both benign conditions like Gilbert’s syndrome and post-hepatitic and toxic conditions that require a long-term regimen and follow-up examinations. The number of people suffering from juvenile hyperbilirubinaemia has been growing in the population. Currently 4-6% of the adolescent population suffers from this disease. This growing number is probably caused by external factors of our environment (infection, toxic effects). The determination of mild liver disease in hyperbilirubinaemic patients and the provision of an adequate regimen of exercise and adequate nutritional measures is of great importance for the health of the adolescent population.
- MeSH
- biliární cirhóza diagnóza chirurgie MeSH
- bilirubin krev MeSH
- cholestáza etiologie patologie MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- hyperbilirubinemie etiologie patologie MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká žloutenka diagnóza etiologie krev MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- MeSH
- aminokyseliny krev MeSH
- dítě MeSH
- fototerapie MeSH
- fyziologie výživy kojenců MeSH
- hyperbilirubinemie krev patologie terapie MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká žloutenka MeSH
- vedení porodu MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- srovnávací studie MeSH
