{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:39:37Z","timestamp":1764700777124},"reference-count":20,"publisher":"Institute of Physiology of the Czech Academy of Sciences","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiol Res"],"published-print":{"date-parts":[[2015,12,28]]},"abstract":"<jats:p>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 \u2013 control, AIA \u2013 untreated adjuvant-induced arthritis, AIA-BIL \u2013 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.<\/jats:p>","DOI":"10.33549\/physiolres.933202","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:14:14Z","timestamp":1587636854000},"page":"S459-S466","source":"Crossref","is-referenced-by-count":3,"title":["Hyperbilirubinemia Decreases Physiological Markers in Adjuvant-Induced Arthritis"],"prefix":"10.33549","author":[{"given":"K.","family":"BAUEROVA","sequence":"first","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"DRAFI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"KUNCIROVA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"PONIST","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"MIHALOVA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"BABAL","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"SYKORA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"19169","published-online":{"date-parts":[[2015,12,12]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"BAUEROVA K, PONIST S, KUNCIROVA V, MIHALOVA D, PAULOVICOVA E, VOLPI N: Chondroitin sulfate effect on induced arthritis in rats. Osteoarthr Cartil 19: 1373-1379, 2011.","DOI":"10.1016\/j.joca.2011.08.006"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"BAUEROVA K, ACQUAVIVA A, PONIST S, GARDI C, VECCHIO D, DRAFI F, AREZZINI B, BEZAKOVA L, KUNCIROVA V, MIHALOVA D, NOSAL R: Markers of inflammation and oxidative stress studied in adjuvant-induced arthritis in the rat on systemic and local level affected by pinosylvin and methotrexate and their combination. Autoimmunity 48: 46-56, 2015.","DOI":"10.3109\/08916934.2014.939268"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"BRITO MA, SILVA R, TIRIBELLI C, BRITES D: Assessment of bilirubin toxicity to erythrocytes. Implication in neonatal jaundice management. Eur J Clin Invest 30: 239-247, 2000.","DOI":"10.1046\/j.1365-2362.2000.00612.x"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"CORCHIA C, BALATA A, SOLETTA G, MASTRONI P, MELONI GF: Increased bilirubin production, ceruloplasmin concentrations and hyperbilirubinaemia in full-term newborn infants. Early Hum Dev 38: 91-96, 1994.","DOI":"10.1016\/0378-3782(94)90220-8"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"FEKETEOVA L, JANCOVA P, MORAVCOVA P, JANEGOVA A, BAUEROVA K, PONIST S, MIHALOVA D, JANEGA P, BABAL P: Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthritis. Rheumatol Int 32: 3517-3523, 2012.","DOI":"10.1007\/s00296-011-2177-3"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"FISCHMAN D, VALLURI A, GORREPATI VS, MURPHY ME, PETERS I, CHERIYATH P: Bilirubin as a protective factor for rheumatoid arthritis: An NHANES Study of 2003-2006 Data. J Clin Med Res 2: 256-260, 2010.","DOI":"10.4021\/jocmr444w"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"GARBER CC: Jendrassik-Grof analysis for total and direct bilirubin in serum with a centrifugal analyzer. Clin Chem 27: 1410-1416, 1981.","DOI":"10.1093\/clinchem\/27.8.1410"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"KADL A, PONTILLER J, EXNER M, LEITIGER N: Single bolus injection of bilirubin improves the clinical outcome in a mouse model of endotoxemia. Shock 28: 582-588, 2007.","DOI":"10.1097\/shk.0b013e31804d41dd"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"KATO Y, SHIMAZU M, KONDO M, UCHIDA K, KUMAMOTO Y, WAKABAYASHI G: Bilirubin rinse: a simple protectant against the rat liver graft injury mimicking heme oxygenase-1 preconditioning. Hepatology 38: 364-373, 2003.","DOI":"10.1053\/jhep.2003.50300"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"KHAN NM, PODUVAL TB: Immunomodulatory and immunotoxic effects of bilirubin: molecular mechanisms. J Leukoc Biol 90: 997-1015, 2011.","DOI":"10.1189\/jlb.0211070"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"KIRKBY KA, ADIN CA: Products of heme oxygenase and their potential therapeutic applications. Am J Physiol Renal Physiol 290: F563-F571, 2006.","DOI":"10.1152\/ajprenal.00220.2005"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"LIU Y, LI P, LU J, XIONG W, OGER J, TETZLAFF W, CYNADER M: Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis. J Immunol 181: 1887-1897, 2008.","DOI":"10.4049\/jimmunol.181.3.1887"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"MCCARTY MF: \u201cIatrogenic Gilbert syndrome\u201d- A strategy for reducing vascular and cancer risk by increasing plasma uncojugated bilirubin. Med Hypotheses 67: 974-994, 2007.","DOI":"10.1016\/j.mehy.2006.12.069"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"MCDONAGH AF: Bilirubin toxicity to human erythrocytes: a more sanguine view. Pediatrics 120: 175-178, 2007.","DOI":"10.1542\/peds.2007-0438"},{"key":"ref14","unstructured":"MURTAZA JVV: Unconjugated hyperbilirubinemia in commercial pilot: A clinical dilemma. Ind J Aerospace Med 53: 53-57, 2009."},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"OLLINGER R, KOGLER P: Bilirubin inhibits tumor cell growth via activation ERK. Cell Cycle 6: 3078-3085, 2007.","DOI":"10.4161\/cc.6.24.5022"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"OLLINGER R, WANG H, YAMASHITA K, WEGIEL B, THOMAS M, MARGREITER R: Therapeutic applications of bilirubin and biliverdin in transplantation. Antioxid Redox Signal 9: 2175-2185, 2007.","DOI":"10.1089\/ars.2007.1807"},{"key":"ref17","unstructured":"PRIBYL T: A modification of the spectrophotometric determination of ceruloplasmin on the basis of its polyphenol oxidase activity. Bioch Clin Bohemoslov 5: 225, 1976."},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"WANG WW, SMITH DL, ZUCKER SD: Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats. Hepatology 40: 424-433, 2004.","DOI":"10.1002\/hep.20334"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"VITEK L: Impact of serum bilirubin on human diseases. 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