Effects of allopurinol and steroids on inflammation and oxidative tissue damage in experimental lens induced uveitis: a biochemical and morphological study
AIMS: To evaluate the effects of allopurinol in lens induced uveitis (LIU) by morphological methods and to compare these effects with those of steroids and a combination of both drugs biochemically and morphologically. METHODS: Lipid peroxides (LPO) of the retinal tissue were determined by two diffe...
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| Veröffentlicht in: | British journal of ophthalmology 1996-05, Vol.80 (5), p.451-457 |
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| creator | Augustin, A J Spitznas, M Sekundo, W Koch, F Lutz, J Meller, D Grus, F H Wegener, A Blumenröder, S H |
| description | AIMS: To evaluate the effects of allopurinol in lens induced uveitis (LIU) by morphological methods and to compare these effects with those of steroids and a combination of both drugs biochemically and morphologically. METHODS: Lipid peroxides (LPO) of the retinal tissue were determined by two different methods (thiobarbituric acid assay (TBA) and high performance liquid chromatography expressed as malondialdehyde-like substances). Myeloperoxidase (MPO) activity in the iris/ciliary body complex was analysed spectrophotometrically. Histological changes on three morphological levels of LIU eyes were evaluated. RESULTS: Both allopurinol and the combination of allopurinol/prednisolone led to a significant reduction in the increaed retinal LPO values. Prednisolone only revealed significant effects on retinal LPO when being measured with the TBA method. MPO activity in iris and ciliary body was significantly reduced in all therapy groups. The morphological evaluation of the sections by two masked investigators revealed a significant reduction (p < 0.05) in the inflammation score in all therapy groups. Morphometric studies using the QUANTIMED system (Leica, Cambridge) showed significantly reduced values (p < 0.05) in the allopurinol group and in the group receiving prednisolone and allopurinol. Prednisolone alone did not lead to a significant reduction in the values. CONCLUSIONS: The findings show that both allopurinol and steroids exert positive effects on the variables determined in LIU. The effects of steroids are believed to be mostly due to their direct action on inflammatory cells. The recently reported scavenging effects of methylprednisolone should play a minor role in this disease model. Allopurinol and oxypurinol act as direct scavengers of free radicals and hypochlorous acid, which is produced via MPO catalysis, thus leading to a reduction in tissue inflammation and tissue damage. |
| doi_str_mv | 10.1136/bjo.80.5.451 |
| format | Article |
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METHODS: Lipid peroxides (LPO) of the retinal tissue were determined by two different methods (thiobarbituric acid assay (TBA) and high performance liquid chromatography expressed as malondialdehyde-like substances). Myeloperoxidase (MPO) activity in the iris/ciliary body complex was analysed spectrophotometrically. Histological changes on three morphological levels of LIU eyes were evaluated. RESULTS: Both allopurinol and the combination of allopurinol/prednisolone led to a significant reduction in the increaed retinal LPO values. Prednisolone only revealed significant effects on retinal LPO when being measured with the TBA method. MPO activity in iris and ciliary body was significantly reduced in all therapy groups. The morphological evaluation of the sections by two masked investigators revealed a significant reduction (p < 0.05) in the inflammation score in all therapy groups. Morphometric studies using the QUANTIMED system (Leica, Cambridge) showed significantly reduced values (p < 0.05) in the allopurinol group and in the group receiving prednisolone and allopurinol. Prednisolone alone did not lead to a significant reduction in the values. CONCLUSIONS: The findings show that both allopurinol and steroids exert positive effects on the variables determined in LIU. The effects of steroids are believed to be mostly due to their direct action on inflammatory cells. The recently reported scavenging effects of methylprednisolone should play a minor role in this disease model. Allopurinol and oxypurinol act as direct scavengers of free radicals and hypochlorous acid, which is produced via MPO catalysis, thus leading to a reduction in tissue inflammation and tissue damage.</description><identifier>ISSN: 0007-1161</identifier><identifier>EISSN: 1468-2079</identifier><identifier>DOI: 10.1136/bjo.80.5.451</identifier><identifier>PMID: 8695568</identifier><identifier>CODEN: BJOPAL</identifier><language>eng</language><publisher>BMA House, Tavistock Square, London, WC1H 9JR: BMJ Publishing Group Ltd</publisher><subject>Allopurinol - therapeutic use ; Animals ; Anti-Inflammatory Agents - therapeutic use ; Chromatography, High Pressure Liquid ; Ciliary Body - enzymology ; Contact Lenses - adverse effects ; Disease Models, Animal ; Drug Therapy, Combination ; Free Radical Scavengers - therapeutic use ; Image Processing, Computer-Assisted ; Iris - enzymology ; Lipid Peroxides - analysis ; Male ; Peroxidase - analysis ; Prednisolone - therapeutic use ; Rats ; Rats, Wistar ; Retina - chemistry ; Uveitis - drug therapy ; Uveitis - etiology ; Uveitis - pathology</subject><ispartof>British journal of ophthalmology, 1996-05, Vol.80 (5), p.451-457</ispartof><rights>Copyright BMJ Publishing Group LTD May 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b476t-566ddef4ec70c9e37ffaecdf78bbc205e31d026b8a44bb3c334552ac1e7afe983</citedby><cites>FETCH-LOGICAL-b476t-566ddef4ec70c9e37ffaecdf78bbc205e31d026b8a44bb3c334552ac1e7afe983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC505498/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC505498/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8695568$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Augustin, A J</creatorcontrib><creatorcontrib>Spitznas, M</creatorcontrib><creatorcontrib>Sekundo, W</creatorcontrib><creatorcontrib>Koch, F</creatorcontrib><creatorcontrib>Lutz, J</creatorcontrib><creatorcontrib>Meller, D</creatorcontrib><creatorcontrib>Grus, F H</creatorcontrib><creatorcontrib>Wegener, A</creatorcontrib><creatorcontrib>Blumenröder, S H</creatorcontrib><title>Effects of allopurinol and steroids on inflammation and oxidative tissue damage in experimental lens induced uveitis: a biochemical and morphological study</title><title>British journal of ophthalmology</title><addtitle>Br J Ophthalmol</addtitle><description>AIMS: To evaluate the effects of allopurinol in lens induced uveitis (LIU) by morphological methods and to compare these effects with those of steroids and a combination of both drugs biochemically and morphologically. METHODS: Lipid peroxides (LPO) of the retinal tissue were determined by two different methods (thiobarbituric acid assay (TBA) and high performance liquid chromatography expressed as malondialdehyde-like substances). Myeloperoxidase (MPO) activity in the iris/ciliary body complex was analysed spectrophotometrically. Histological changes on three morphological levels of LIU eyes were evaluated. RESULTS: Both allopurinol and the combination of allopurinol/prednisolone led to a significant reduction in the increaed retinal LPO values. Prednisolone only revealed significant effects on retinal LPO when being measured with the TBA method. MPO activity in iris and ciliary body was significantly reduced in all therapy groups. The morphological evaluation of the sections by two masked investigators revealed a significant reduction (p < 0.05) in the inflammation score in all therapy groups. Morphometric studies using the QUANTIMED system (Leica, Cambridge) showed significantly reduced values (p < 0.05) in the allopurinol group and in the group receiving prednisolone and allopurinol. Prednisolone alone did not lead to a significant reduction in the values. CONCLUSIONS: The findings show that both allopurinol and steroids exert positive effects on the variables determined in LIU. The effects of steroids are believed to be mostly due to their direct action on inflammatory cells. The recently reported scavenging effects of methylprednisolone should play a minor role in this disease model. Allopurinol and oxypurinol act as direct scavengers of free radicals and hypochlorous acid, which is produced via MPO catalysis, thus leading to a reduction in tissue inflammation and tissue damage.</description><subject>Allopurinol - therapeutic use</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Ciliary Body - enzymology</subject><subject>Contact Lenses - adverse effects</subject><subject>Disease Models, Animal</subject><subject>Drug Therapy, Combination</subject><subject>Free Radical Scavengers - therapeutic use</subject><subject>Image Processing, Computer-Assisted</subject><subject>Iris - enzymology</subject><subject>Lipid Peroxides - analysis</subject><subject>Male</subject><subject>Peroxidase - analysis</subject><subject>Prednisolone - therapeutic use</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Retina - chemistry</subject><subject>Uveitis - drug therapy</subject><subject>Uveitis - etiology</subject><subject>Uveitis - pathology</subject><issn>0007-1161</issn><issn>1468-2079</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU2P0zAQhi0EWsrCjSuSJSS4kGLXcZwicUDV8iEtH4cFob1Yjj1uXZw42EnV_S38WdxNVQEHTtbM-4zfGb0IPaZkTimrXjbbMK_JnM9LTu-gGS2rulgQsbyLZoQQUVBa0fvoQUrbXC4qKs7QWV0tOa_qGfp1YS3oIeFgsfI-9GN0XfBYdQanAWJwJmsddp31qm3V4HJxEMPemVztAA8upRGwUa1aQwYx7HuIroVuUB576FJumlGDweMOXMZfYYUbF_QGWqfVZNaG2G-CD-vbThpGc_MQ3bPKJ3h0fM_R17cXV6v3xeXndx9Wby6LphTVUPCqMgZsCVoQvQQmrFWgjRV10-gF4cCoyXc3tSrLpmGasZLzhdIUhLKwrNk5ej39249NC0bnxaPyss83qHgjg3Lyb6VzG7kOO8kJL2_nnx3nY_g5Qhpk65IG71UHYUxS1JSVhJIMPv0H3IYxdvk2SYUghAnODtSLidIxpBTBnjahRB4SlzlxWRPJZU4840_-3P4EHyPOejHpLue5P8kq_pCVyI7y07eV_H69-ijY9ZX8kvnnE9-02_87_wa3VMjy</recordid><startdate>19960501</startdate><enddate>19960501</enddate><creator>Augustin, A J</creator><creator>Spitznas, M</creator><creator>Sekundo, W</creator><creator>Koch, F</creator><creator>Lutz, J</creator><creator>Meller, D</creator><creator>Grus, F H</creator><creator>Wegener, A</creator><creator>Blumenröder, S H</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960501</creationdate><title>Effects of allopurinol and steroids on inflammation and oxidative tissue damage in experimental lens induced uveitis: a biochemical and morphological study</title><author>Augustin, A J ; Spitznas, M ; Sekundo, W ; Koch, F ; Lutz, J ; Meller, D ; Grus, F H ; Wegener, A ; Blumenröder, S H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b476t-566ddef4ec70c9e37ffaecdf78bbc205e31d026b8a44bb3c334552ac1e7afe983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Allopurinol - therapeutic use</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Ciliary Body - enzymology</topic><topic>Contact Lenses - adverse effects</topic><topic>Disease Models, Animal</topic><topic>Drug Therapy, Combination</topic><topic>Free Radical Scavengers - therapeutic use</topic><topic>Image Processing, Computer-Assisted</topic><topic>Iris - enzymology</topic><topic>Lipid Peroxides - analysis</topic><topic>Male</topic><topic>Peroxidase - analysis</topic><topic>Prednisolone - therapeutic use</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Retina - chemistry</topic><topic>Uveitis - drug therapy</topic><topic>Uveitis - etiology</topic><topic>Uveitis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Augustin, A J</creatorcontrib><creatorcontrib>Spitznas, M</creatorcontrib><creatorcontrib>Sekundo, W</creatorcontrib><creatorcontrib>Koch, F</creatorcontrib><creatorcontrib>Lutz, J</creatorcontrib><creatorcontrib>Meller, D</creatorcontrib><creatorcontrib>Grus, F H</creatorcontrib><creatorcontrib>Wegener, A</creatorcontrib><creatorcontrib>Blumenröder, S H</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Augustin, A J</au><au>Spitznas, M</au><au>Sekundo, W</au><au>Koch, F</au><au>Lutz, J</au><au>Meller, D</au><au>Grus, F H</au><au>Wegener, A</au><au>Blumenröder, S H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of allopurinol and steroids on inflammation and oxidative tissue damage in experimental lens induced uveitis: a biochemical and morphological study</atitle><jtitle>British journal of ophthalmology</jtitle><addtitle>Br J Ophthalmol</addtitle><date>1996-05-01</date><risdate>1996</risdate><volume>80</volume><issue>5</issue><spage>451</spage><epage>457</epage><pages>451-457</pages><issn>0007-1161</issn><eissn>1468-2079</eissn><coden>BJOPAL</coden><abstract>AIMS: To evaluate the effects of allopurinol in lens induced uveitis (LIU) by morphological methods and to compare these effects with those of steroids and a combination of both drugs biochemically and morphologically. METHODS: Lipid peroxides (LPO) of the retinal tissue were determined by two different methods (thiobarbituric acid assay (TBA) and high performance liquid chromatography expressed as malondialdehyde-like substances). Myeloperoxidase (MPO) activity in the iris/ciliary body complex was analysed spectrophotometrically. Histological changes on three morphological levels of LIU eyes were evaluated. RESULTS: Both allopurinol and the combination of allopurinol/prednisolone led to a significant reduction in the increaed retinal LPO values. Prednisolone only revealed significant effects on retinal LPO when being measured with the TBA method. MPO activity in iris and ciliary body was significantly reduced in all therapy groups. The morphological evaluation of the sections by two masked investigators revealed a significant reduction (p < 0.05) in the inflammation score in all therapy groups. Morphometric studies using the QUANTIMED system (Leica, Cambridge) showed significantly reduced values (p < 0.05) in the allopurinol group and in the group receiving prednisolone and allopurinol. Prednisolone alone did not lead to a significant reduction in the values. CONCLUSIONS: The findings show that both allopurinol and steroids exert positive effects on the variables determined in LIU. The effects of steroids are believed to be mostly due to their direct action on inflammatory cells. The recently reported scavenging effects of methylprednisolone should play a minor role in this disease model. Allopurinol and oxypurinol act as direct scavengers of free radicals and hypochlorous acid, which is produced via MPO catalysis, thus leading to a reduction in tissue inflammation and tissue damage.</abstract><cop>BMA House, Tavistock Square, London, WC1H 9JR</cop><pub>BMJ Publishing Group Ltd</pub><pmid>8695568</pmid><doi>10.1136/bjo.80.5.451</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Allopurinol - therapeutic use Animals Anti-Inflammatory Agents - therapeutic use Chromatography, High Pressure Liquid Ciliary Body - enzymology Contact Lenses - adverse effects Disease Models, Animal Drug Therapy, Combination Free Radical Scavengers - therapeutic use Image Processing, Computer-Assisted Iris - enzymology Lipid Peroxides - analysis Male Peroxidase - analysis Prednisolone - therapeutic use Rats Rats, Wistar Retina - chemistry Uveitis - drug therapy Uveitis - etiology Uveitis - pathology |
| title | Effects of allopurinol and steroids on inflammation and oxidative tissue damage in experimental lens induced uveitis: a biochemical and morphological study |
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