Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis
Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)—an experimental model, in which oxidative stress (OS), inflamma...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8662 |
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| author | Tomas Sykora Pavel Babal Kristina Mikus-Kuracinova Frantisek Drafi Silvester Ponist Monika Dvorakova Pavol Janega Katarina Bauerova |
| author_facet | Tomas Sykora Pavel Babal Kristina Mikus-Kuracinova Frantisek Drafi Silvester Ponist Monika Dvorakova Pavol Janega Katarina Bauerova |
| author_sort | Tomas Sykora |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)—an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO—control, AIA—untreated adjuvant-induced arthritis, AIA-BIL—adjuvant-induced arthritis administrated UCB, CO-BIL—control with administrated UCB. UCB was administered <i>intraperitoneally</i> 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of <i>Mycobacterium butyricum</i> in incomplete Freund’s adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic. |
| first_indexed | 2024-03-10T08:44:38Z |
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| id | doaj.art-39958f5c803c40e28fcebb86614a2eba |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:38Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-39958f5c803c40e28fcebb86614a2eba2023-11-22T07:58:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216866210.3390/ijms22168662Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune ArthritisTomas Sykora0Pavel Babal1Kristina Mikus-Kuracinova2Frantisek Drafi3Silvester Ponist4Monika Dvorakova5Pavol Janega6Katarina Bauerova7Department of Pathology, Faculty of Medicine, Comenius University in Bratislava, Spitalska 24, 81372 Bratislava, SlovakiaDepartment of Pathology, Faculty of Medicine, Comenius University in Bratislava, Spitalska 24, 81372 Bratislava, SlovakiaDepartment of Pathology, Faculty of Medicine, Comenius University in Bratislava, Spitalska 24, 81372 Bratislava, SlovakiaCentre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 84104 Bratislava, SlovakiaCentre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 84104 Bratislava, SlovakiaDepartment of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University in Bratislava, Spitalska 24, 81372 Bratislava, SlovakiaDepartment of Pathology, Faculty of Medicine, Comenius University in Bratislava, Spitalska 24, 81372 Bratislava, SlovakiaCentre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 84104 Bratislava, SlovakiaRheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)—an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO—control, AIA—untreated adjuvant-induced arthritis, AIA-BIL—adjuvant-induced arthritis administrated UCB, CO-BIL—control with administrated UCB. UCB was administered <i>intraperitoneally</i> 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of <i>Mycobacterium butyricum</i> in incomplete Freund’s adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.https://www.mdpi.com/1422-0067/22/16/8662adjuvant-induced arthritisbilirubinimmunomodulationinflammationwhite blood cells |
| spellingShingle | Tomas Sykora Pavel Babal Kristina Mikus-Kuracinova Frantisek Drafi Silvester Ponist Monika Dvorakova Pavol Janega Katarina Bauerova Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis International Journal of Molecular Sciences adjuvant-induced arthritis bilirubin immunomodulation inflammation white blood cells |
| title | Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis |
| title_full | Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis |
| title_fullStr | Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis |
| title_full_unstemmed | Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis |
| title_short | Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis |
| title_sort | hyperbilirubinemia maintained by chronic supplementation of unconjugated bilirubin improves the clinical course of experimental autoimmune arthritis |
| topic | adjuvant-induced arthritis bilirubin immunomodulation inflammation white blood cells |
| url | https://www.mdpi.com/1422-0067/22/16/8662 |
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