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Uroprotective Effect of Pentoxifylline in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats
ABSTRACT The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide‐induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxi...
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| Published in: | Journal of biochemical and molecular toxicology 2013-07, Vol.27 (7), p.343-350 |
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| container_title | Journal of biochemical and molecular toxicology |
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| creator | Abo-Salem, Osama M. |
| description | ABSTRACT
The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide‐induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxifylline (150 mg/kg/day/ip) was administered for 10 days followed by cyclophosphamide. Hemorrhagic cystitis was well characterized macroscopically, microscopically, and biochemically. Cyclophosphamide induced bladder injury including acute severe inflammation, vascular congestion, severe edema, hemorrhage, inflammatory cell infiltration in the lamina propria, and epithelial denudation; as well as it notably elevated serum inflammatory cytokines (tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β), bladder content of malondialdehyde and total nitrate, accompanied with depletion of bladder antioxidant enzymes activities (glutathione peroxidase, superoxide dismutase, glutathione‐S‐transferase, and catalase). Prior administration of pentoxifylline improved all biochemical and histologic alterations induced by the cytotoxic drug cyclophosphamide. In conclusion, pentoxifylline has proven uroprotective efficacy in the cyclophosphamide‐induced hemorrhagic cystitis model, possibly through modulating the release of inflammatory cytokines and nitric oxide and restoring the oxidant/antioxidant balance. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:343‐350, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21494 |
| doi_str_mv | 10.1002/jbt.21494 |
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The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide‐induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxifylline (150 mg/kg/day/ip) was administered for 10 days followed by cyclophosphamide. Hemorrhagic cystitis was well characterized macroscopically, microscopically, and biochemically. Cyclophosphamide induced bladder injury including acute severe inflammation, vascular congestion, severe edema, hemorrhage, inflammatory cell infiltration in the lamina propria, and epithelial denudation; as well as it notably elevated serum inflammatory cytokines (tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β), bladder content of malondialdehyde and total nitrate, accompanied with depletion of bladder antioxidant enzymes activities (glutathione peroxidase, superoxide dismutase, glutathione‐S‐transferase, and catalase). Prior administration of pentoxifylline improved all biochemical and histologic alterations induced by the cytotoxic drug cyclophosphamide. In conclusion, pentoxifylline has proven uroprotective efficacy in the cyclophosphamide‐induced hemorrhagic cystitis model, possibly through modulating the release of inflammatory cytokines and nitric oxide and restoring the oxidant/antioxidant balance. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:343‐350, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21494</description><identifier>ISSN: 1095-6670</identifier><identifier>EISSN: 1099-0461</identifier><identifier>DOI: 10.1002/jbt.21494</identifier><identifier>PMID: 23695977</identifier><identifier>CODEN: JBMTFQ</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Antineoplastic Agents, Alkylating - adverse effects ; Antineoplastic Agents, Alkylating - pharmacology ; Antioxidants - metabolism ; Cyclophosphamide ; Cyclophosphamide - adverse effects ; Cyclophosphamide - pharmacology ; Cystitis - blood ; Cystitis - chemically induced ; Cystitis - pathology ; Cystitis - prevention & control ; Cytokines - blood ; Disease Models, Animal ; Free Radical Scavengers - pharmacology ; Hemorrhage - blood ; Hemorrhage - chemically induced ; Hemorrhage - pathology ; Hemorrhage - prevention & control ; Hemorrhagic Cystitis ; Malondialdehyde - metabolism ; Nitric Oxide - metabolism ; Oxidoreductases - metabolism ; Pentoxifylline ; Pentoxifylline - pharmacokinetics ; Rats ; Urinary Bladder - metabolism ; Urinary Bladder - pathology ; Uroprotective</subject><ispartof>Journal of biochemical and molecular toxicology, 2013-07, Vol.27 (7), p.343-350</ispartof><rights>2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4244-1788be7ba476a7d5dad2dcf62c564796f2e9f55d209301d182a44ebc407b27ee3</citedby><cites>FETCH-LOGICAL-c4244-1788be7ba476a7d5dad2dcf62c564796f2e9f55d209301d182a44ebc407b27ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23695977$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abo-Salem, Osama M.</creatorcontrib><title>Uroprotective Effect of Pentoxifylline in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats</title><title>Journal of biochemical and molecular toxicology</title><addtitle>J Biochem Mol Toxicol</addtitle><description>ABSTRACT
The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide‐induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxifylline (150 mg/kg/day/ip) was administered for 10 days followed by cyclophosphamide. Hemorrhagic cystitis was well characterized macroscopically, microscopically, and biochemically. Cyclophosphamide induced bladder injury including acute severe inflammation, vascular congestion, severe edema, hemorrhage, inflammatory cell infiltration in the lamina propria, and epithelial denudation; as well as it notably elevated serum inflammatory cytokines (tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β), bladder content of malondialdehyde and total nitrate, accompanied with depletion of bladder antioxidant enzymes activities (glutathione peroxidase, superoxide dismutase, glutathione‐S‐transferase, and catalase). Prior administration of pentoxifylline improved all biochemical and histologic alterations induced by the cytotoxic drug cyclophosphamide. In conclusion, pentoxifylline has proven uroprotective efficacy in the cyclophosphamide‐induced hemorrhagic cystitis model, possibly through modulating the release of inflammatory cytokines and nitric oxide and restoring the oxidant/antioxidant balance. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:343‐350, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21494</description><subject>Animals</subject><subject>Antineoplastic Agents, Alkylating - adverse effects</subject><subject>Antineoplastic Agents, Alkylating - pharmacology</subject><subject>Antioxidants - metabolism</subject><subject>Cyclophosphamide</subject><subject>Cyclophosphamide - adverse effects</subject><subject>Cyclophosphamide - pharmacology</subject><subject>Cystitis - blood</subject><subject>Cystitis - chemically induced</subject><subject>Cystitis - pathology</subject><subject>Cystitis - prevention & control</subject><subject>Cytokines - blood</subject><subject>Disease Models, Animal</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Hemorrhage - blood</subject><subject>Hemorrhage - chemically induced</subject><subject>Hemorrhage - pathology</subject><subject>Hemorrhage - prevention & control</subject><subject>Hemorrhagic Cystitis</subject><subject>Malondialdehyde - metabolism</subject><subject>Nitric Oxide - metabolism</subject><subject>Oxidoreductases - metabolism</subject><subject>Pentoxifylline</subject><subject>Pentoxifylline - pharmacokinetics</subject><subject>Rats</subject><subject>Urinary Bladder - metabolism</subject><subject>Urinary Bladder - pathology</subject><subject>Uroprotective</subject><issn>1095-6670</issn><issn>1099-0461</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqF0U1P3DAQBmALtSoUeugfqCL10h4C_oodH9sFFhAChEAcLceedL1N4q2dFPbf17DAoVLV08zhmVcavQh9JHifYEwPls24TwlXfAvtEKxUibkgb572qhRC4m30PqUlxrhSsnqHtikTKq9yB-nbGFYxjGBH_xuKo7bNWxHa4gqGMTz4dt11foDCD8VsbbuwWoS0WpjeOyhPBzdZcMUJ9CHGhfnhbUZp9KNPjwfXZkx76G1rugQfnucuuj0-upmdlOeX89PZt_PScsp5SWRdNyAbw6Uw0lXOOOpsK6itBJdKtBRUW1WOYsUwcaSmhnNoLMeyoRKA7aIvm9z8zK8J0qh7nyx0nRkgTEkTzjhmjLP6_5QpJmtJa5zp57_oMkxxyI9kJRnlmCuR1deNsjGkFKHVq-h7E9eaYP1YkM4F6aeCsv30nDg1PbhX-dJIBgcbcO87WP87SZ99v3mJLDcXPo3w8Hph4k8tJJOVvruY64uzw-v54YzqK_YHt7yo9A</recordid><startdate>201307</startdate><enddate>201307</enddate><creator>Abo-Salem, Osama M.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201307</creationdate><title>Uroprotective Effect of Pentoxifylline in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats</title><author>Abo-Salem, Osama M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4244-1788be7ba476a7d5dad2dcf62c564796f2e9f55d209301d182a44ebc407b27ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Alkylating - adverse effects</topic><topic>Antineoplastic Agents, Alkylating - pharmacology</topic><topic>Antioxidants - metabolism</topic><topic>Cyclophosphamide</topic><topic>Cyclophosphamide - adverse effects</topic><topic>Cyclophosphamide - pharmacology</topic><topic>Cystitis - blood</topic><topic>Cystitis - chemically induced</topic><topic>Cystitis - pathology</topic><topic>Cystitis - prevention & control</topic><topic>Cytokines - blood</topic><topic>Disease Models, Animal</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Hemorrhage - blood</topic><topic>Hemorrhage - chemically induced</topic><topic>Hemorrhage - pathology</topic><topic>Hemorrhage - prevention & control</topic><topic>Hemorrhagic Cystitis</topic><topic>Malondialdehyde - metabolism</topic><topic>Nitric Oxide - metabolism</topic><topic>Oxidoreductases - metabolism</topic><topic>Pentoxifylline</topic><topic>Pentoxifylline - pharmacokinetics</topic><topic>Rats</topic><topic>Urinary Bladder - metabolism</topic><topic>Urinary Bladder - pathology</topic><topic>Uroprotective</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abo-Salem, Osama M.</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>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biochemical and molecular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abo-Salem, Osama M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Uroprotective Effect of Pentoxifylline in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats</atitle><jtitle>Journal of biochemical and molecular toxicology</jtitle><addtitle>J Biochem Mol Toxicol</addtitle><date>2013-07</date><risdate>2013</risdate><volume>27</volume><issue>7</issue><spage>343</spage><epage>350</epage><pages>343-350</pages><issn>1095-6670</issn><eissn>1099-0461</eissn><coden>JBMTFQ</coden><abstract>ABSTRACT
The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide‐induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxifylline (150 mg/kg/day/ip) was administered for 10 days followed by cyclophosphamide. Hemorrhagic cystitis was well characterized macroscopically, microscopically, and biochemically. Cyclophosphamide induced bladder injury including acute severe inflammation, vascular congestion, severe edema, hemorrhage, inflammatory cell infiltration in the lamina propria, and epithelial denudation; as well as it notably elevated serum inflammatory cytokines (tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β), bladder content of malondialdehyde and total nitrate, accompanied with depletion of bladder antioxidant enzymes activities (glutathione peroxidase, superoxide dismutase, glutathione‐S‐transferase, and catalase). Prior administration of pentoxifylline improved all biochemical and histologic alterations induced by the cytotoxic drug cyclophosphamide. In conclusion, pentoxifylline has proven uroprotective efficacy in the cyclophosphamide‐induced hemorrhagic cystitis model, possibly through modulating the release of inflammatory cytokines and nitric oxide and restoring the oxidant/antioxidant balance. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:343‐350, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21494</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23695977</pmid><doi>10.1002/jbt.21494</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Antineoplastic Agents, Alkylating - adverse effects Antineoplastic Agents, Alkylating - pharmacology Antioxidants - metabolism Cyclophosphamide Cyclophosphamide - adverse effects Cyclophosphamide - pharmacology Cystitis - blood Cystitis - chemically induced Cystitis - pathology Cystitis - prevention & control Cytokines - blood Disease Models, Animal Free Radical Scavengers - pharmacology Hemorrhage - blood Hemorrhage - chemically induced Hemorrhage - pathology Hemorrhage - prevention & control Hemorrhagic Cystitis Malondialdehyde - metabolism Nitric Oxide - metabolism Oxidoreductases - metabolism Pentoxifylline Pentoxifylline - pharmacokinetics Rats Urinary Bladder - metabolism Urinary Bladder - pathology Uroprotective |
| title | Uroprotective Effect of Pentoxifylline in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats |
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