Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats
Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to...
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| Veröffentlicht in: | Human & experimental toxicology 2018-08, Vol.37 (8), p.848-858 |
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| creator | Rjiba-Touati, K Amara, I Bousabbeh, M Salem, I Ben Azzebi, A Guedri, Y Achour, A Bacha, H Abid, S |
| description | Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo. |
| doi_str_mv | 10.1177/0960327117733553 |
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However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.</description><identifier>ISSN: 0960-3271</identifier><identifier>EISSN: 1477-0903</identifier><identifier>DOI: 10.1177/0960327117733553</identifier><identifier>PMID: 29069929</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Antineoplastic drugs ; Antitumor agents ; Biocompatibility ; Catalase ; Damage prevention ; Deoxyribonucleic acid ; DNA ; DNA damage ; Drugs ; Erythropoietin ; Etoposide ; Genotoxicity ; Glutathione ; Glycoproteins ; Immunomodulators ; In vivo methods and tests ; Kidneys ; Liver ; Malondialdehyde ; Methotrexate ; Oxidative stress ; Pretreatment ; Rats ; Rodents ; Tissues ; Toxicity</subject><ispartof>Human & experimental toxicology, 2018-08, Vol.37 (8), p.848-858</ispartof><rights>The Author(s) 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-22787e7b19bc3bb366092786cf541070cf7515c5ec44a1b0832e1414fcaeb0ed3</citedby><cites>FETCH-LOGICAL-c365t-22787e7b19bc3bb366092786cf541070cf7515c5ec44a1b0832e1414fcaeb0ed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0960327117733553$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0960327117733553$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21945,27830,27901,27902,44921,45309</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0960327117733553?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29069929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rjiba-Touati, K</creatorcontrib><creatorcontrib>Amara, I</creatorcontrib><creatorcontrib>Bousabbeh, M</creatorcontrib><creatorcontrib>Salem, I Ben</creatorcontrib><creatorcontrib>Azzebi, A</creatorcontrib><creatorcontrib>Guedri, Y</creatorcontrib><creatorcontrib>Achour, A</creatorcontrib><creatorcontrib>Bacha, H</creatorcontrib><creatorcontrib>Abid, S</creatorcontrib><title>Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats</title><title>Human & experimental toxicology</title><addtitle>Hum Exp Toxicol</addtitle><description>Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.</description><subject>Antineoplastic drugs</subject><subject>Antitumor agents</subject><subject>Biocompatibility</subject><subject>Catalase</subject><subject>Damage prevention</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Drugs</subject><subject>Erythropoietin</subject><subject>Etoposide</subject><subject>Genotoxicity</subject><subject>Glutathione</subject><subject>Glycoproteins</subject><subject>Immunomodulators</subject><subject>In vivo methods and tests</subject><subject>Kidneys</subject><subject>Liver</subject><subject>Malondialdehyde</subject><subject>Methotrexate</subject><subject>Oxidative stress</subject><subject>Pretreatment</subject><subject>Rats</subject><subject>Rodents</subject><subject>Tissues</subject><subject>Toxicity</subject><issn>0960-3271</issn><issn>1477-0903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kU9PGzEQxa2KqgTaOydkifNSe727jo8VKn8kpEqoiOPKa88mTrN2as9G5KPx7XBIKBUSJ49nfu-N5UfICWfnnEv5namGiVJuayHqWnwiE15JWTDFxAGZbMfFdn5IjlJaMMYaVfMv5LBUuVKlmpCnOzBh6JzXHul8HLSnEDc4j2EVHKDzdBVhDR4TBcy95CwUVHtLB8B5wAiPGqFw3o4GLMXw6IzDDc3CP8562LywS7eGSNGlNEKia6cpzoFGmI1LjS54GnqalTZf1kCtHvQMXoQz8OF_zweXUEcaNaav5HOvlwm-7c9jcn_58_fFdXH76-rm4sdtYURTY1GWcipBdlx1RnSdaBqmcqsxfV1xJpnpZc1rU4OpKs07NhUl8IpXvdHQMbDimJztfFcx_M3Px3YRxujzyrZkkitZTpXIFNtRJoaUIvTtKrpBx03LWbvNp32fVZac7o3HbgD7T_AaTgaKHZDyd7xt_dDwGdjtoMk</recordid><startdate>201808</startdate><enddate>201808</enddate><creator>Rjiba-Touati, K</creator><creator>Amara, I</creator><creator>Bousabbeh, M</creator><creator>Salem, I Ben</creator><creator>Azzebi, A</creator><creator>Guedri, Y</creator><creator>Achour, A</creator><creator>Bacha, H</creator><creator>Abid, S</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>SOI</scope></search><sort><creationdate>201808</creationdate><title>Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats</title><author>Rjiba-Touati, K ; Amara, I ; Bousabbeh, M ; Salem, I Ben ; Azzebi, A ; Guedri, Y ; Achour, A ; Bacha, H ; Abid, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-22787e7b19bc3bb366092786cf541070cf7515c5ec44a1b0832e1414fcaeb0ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antineoplastic drugs</topic><topic>Antitumor agents</topic><topic>Biocompatibility</topic><topic>Catalase</topic><topic>Damage prevention</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Drugs</topic><topic>Erythropoietin</topic><topic>Etoposide</topic><topic>Genotoxicity</topic><topic>Glutathione</topic><topic>Glycoproteins</topic><topic>Immunomodulators</topic><topic>In vivo methods and tests</topic><topic>Kidneys</topic><topic>Liver</topic><topic>Malondialdehyde</topic><topic>Methotrexate</topic><topic>Oxidative stress</topic><topic>Pretreatment</topic><topic>Rats</topic><topic>Rodents</topic><topic>Tissues</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rjiba-Touati, K</creatorcontrib><creatorcontrib>Amara, I</creatorcontrib><creatorcontrib>Bousabbeh, M</creatorcontrib><creatorcontrib>Salem, I Ben</creatorcontrib><creatorcontrib>Azzebi, A</creatorcontrib><creatorcontrib>Guedri, Y</creatorcontrib><creatorcontrib>Achour, A</creatorcontrib><creatorcontrib>Bacha, H</creatorcontrib><creatorcontrib>Abid, S</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Environment Abstracts</collection><jtitle>Human & experimental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Rjiba-Touati, K</au><au>Amara, I</au><au>Bousabbeh, M</au><au>Salem, I Ben</au><au>Azzebi, A</au><au>Guedri, Y</au><au>Achour, A</au><au>Bacha, H</au><au>Abid, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats</atitle><jtitle>Human & experimental toxicology</jtitle><addtitle>Hum Exp Toxicol</addtitle><date>2018-08</date><risdate>2018</risdate><volume>37</volume><issue>8</issue><spage>848</spage><epage>858</epage><pages>848-858</pages><issn>0960-3271</issn><eissn>1477-0903</eissn><abstract>Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>29069929</pmid><doi>10.1177/0960327117733553</doi><tpages>11</tpages></addata></record> |
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| ispartof | Human & experimental toxicology, 2018-08, Vol.37 (8), p.848-858 |
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| source | Sage Journals GOLD Open Access 2024 |
| subjects | Antineoplastic drugs Antitumor agents Biocompatibility Catalase Damage prevention Deoxyribonucleic acid DNA DNA damage Drugs Erythropoietin Etoposide Genotoxicity Glutathione Glycoproteins Immunomodulators In vivo methods and tests Kidneys Liver Malondialdehyde Methotrexate Oxidative stress Pretreatment Rats Rodents Tissues Toxicity |
| title | Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats |
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