Immunohematotoxicity studies with combinations of dapsone and zidovudine
We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of Pneumocystis carinii infection in AIDS patients. We examined the impact of con...
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| Veröffentlicht in: | International immunopharmacology 2001-11, Vol.1 (12), p.2131-2141 |
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| creator | Freund, Yvonne R Dousman, Linda Riccio, Edward S Sato, Barbara MacGregor, James T Mohagheghpour, Nahid |
| description | We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of
Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (
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| doi_str_mv | 10.1016/S1567-5769(01)00138-2 |
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Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (
P<0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was ≥35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (
P<0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/S1567-5769(01)00138-2</identifier><identifier>PMID: 11710542</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject><![CDATA[AIDS-Related Opportunistic Infections - prevention & control ; Anemia - chemically induced ; Animals ; Anti-HIV Agents - administration & dosage ; Anti-HIV Agents - toxicity ; antiparasitic agents ; antiprotozoal agents ; Antiprotozoal Agents - administration & dosage ; Antiprotozoal Agents - toxicity ; AZT ; Biological and medical sciences ; Bone Marrow - drug effects ; Combination therapy ; Concanavalin A - pharmacology ; Dapsone ; Dapsone - administration & dosage ; Dapsone - analogs & derivatives ; Dapsone - blood ; Dapsone - toxicity ; DDS ; Dose-Response Relationship, Drug ; Drug Interactions ; Drug toxicity and drugs side effects treatment ; Female ; Hematotoxicity ; Leukopenia - chemically induced ; Lymph Nodes - drug effects ; Lymphocyte Activation - drug effects ; Medical sciences ; Methemoglobinemia - chemically induced ; Mice ; Mice, Inbred BALB C ; Neutropenia - chemically induced ; Pharmacology. Drug treatments ; Pneumocystis carinii ; Pneumonia, Pneumocystis - prevention & control ; Thrombocytosis - chemically induced ; Thymus Gland - drug effects ; Toxicity: blood ; ZDV ; Zidovudine ; Zidovudine - administration & dosage ; Zidovudine - toxicity]]></subject><ispartof>International immunopharmacology, 2001-11, Vol.1 (12), p.2131-2141</ispartof><rights>2001 Elsevier Science B.V.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c370t-4b0717b1b775718167d09c3aa8f3f5f20249af980b17106ff44d136d98281c353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1567-5769(01)00138-2$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14075346$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11710542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freund, Yvonne R</creatorcontrib><creatorcontrib>Dousman, Linda</creatorcontrib><creatorcontrib>Riccio, Edward S</creatorcontrib><creatorcontrib>Sato, Barbara</creatorcontrib><creatorcontrib>MacGregor, James T</creatorcontrib><creatorcontrib>Mohagheghpour, Nahid</creatorcontrib><title>Immunohematotoxicity studies with combinations of dapsone and zidovudine</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of
Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (
P<0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was ≥35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (
P<0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV.</description><subject>AIDS-Related Opportunistic Infections - prevention & control</subject><subject>Anemia - chemically induced</subject><subject>Animals</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Anti-HIV Agents - toxicity</subject><subject>antiparasitic agents</subject><subject>antiprotozoal agents</subject><subject>Antiprotozoal Agents - administration & dosage</subject><subject>Antiprotozoal Agents - toxicity</subject><subject>AZT</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow - drug effects</subject><subject>Combination therapy</subject><subject>Concanavalin A - pharmacology</subject><subject>Dapsone</subject><subject>Dapsone - administration & dosage</subject><subject>Dapsone - analogs & derivatives</subject><subject>Dapsone - blood</subject><subject>Dapsone - toxicity</subject><subject>DDS</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Interactions</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Female</subject><subject>Hematotoxicity</subject><subject>Leukopenia - chemically induced</subject><subject>Lymph Nodes - drug effects</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Medical sciences</subject><subject>Methemoglobinemia - chemically induced</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neutropenia - chemically induced</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumocystis carinii</subject><subject>Pneumonia, Pneumocystis - prevention & control</subject><subject>Thrombocytosis - chemically induced</subject><subject>Thymus Gland - drug effects</subject><subject>Toxicity: blood</subject><subject>ZDV</subject><subject>Zidovudine</subject><subject>Zidovudine - administration & dosage</subject><subject>Zidovudine - toxicity</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1PwyAYwHFiNDpfPoKmF40eqjwtFHoyxqhbssSDeiaUl4hZYRY6nZ_ezs149ASH3wNP_ggdA74EDNXVE9CK5ZRV9TmGC4yh5HmxhUbAGc-BYbo93H_JHtqP8W1ADBPYRXsADDAlxQiNJ23b-_BqWplCCp9OubTMYuq1MzH7cOk1U6FtnJfJBR-zYDMt5zF4k0mvsy-nw2Kw3hyiHStn0RxtzgP0cn_3fDvOp48Pk9ubaa5KhlNOGsyANdAwRhlwqJjGtSql5La01Ba4ILW0NcfNasXKWkI0lJWuecFBlbQ8QGfrd-ddeO9NTKJ1UZnZTHoT-iiAFwUBxgdI11B1IcbOWDHvXCu7pQAsVgnFT0Kx6iMwiJ-EohjmTjYf9E1r9N_UptkATjdARiVntpNeufjnCGa0JNXgrtfODDkWznQiKme8Mtp1RiWhg_tnlW-ubY02</recordid><startdate>20011101</startdate><enddate>20011101</enddate><creator>Freund, Yvonne R</creator><creator>Dousman, Linda</creator><creator>Riccio, Edward S</creator><creator>Sato, Barbara</creator><creator>MacGregor, James T</creator><creator>Mohagheghpour, Nahid</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</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>7T5</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20011101</creationdate><title>Immunohematotoxicity studies with combinations of dapsone and zidovudine</title><author>Freund, Yvonne R ; Dousman, Linda ; Riccio, Edward S ; Sato, Barbara ; MacGregor, James T ; Mohagheghpour, Nahid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-4b0717b1b775718167d09c3aa8f3f5f20249af980b17106ff44d136d98281c353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>AIDS-Related Opportunistic Infections - prevention & control</topic><topic>Anemia - chemically induced</topic><topic>Animals</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Anti-HIV Agents - toxicity</topic><topic>antiparasitic agents</topic><topic>antiprotozoal agents</topic><topic>Antiprotozoal Agents - administration & dosage</topic><topic>Antiprotozoal Agents - toxicity</topic><topic>AZT</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow - drug effects</topic><topic>Combination therapy</topic><topic>Concanavalin A - pharmacology</topic><topic>Dapsone</topic><topic>Dapsone - administration & dosage</topic><topic>Dapsone - analogs & derivatives</topic><topic>Dapsone - blood</topic><topic>Dapsone - toxicity</topic><topic>DDS</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Interactions</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Female</topic><topic>Hematotoxicity</topic><topic>Leukopenia - chemically induced</topic><topic>Lymph Nodes - drug effects</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Medical sciences</topic><topic>Methemoglobinemia - chemically induced</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neutropenia - chemically induced</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumocystis carinii</topic><topic>Pneumonia, Pneumocystis - prevention & control</topic><topic>Thrombocytosis - chemically induced</topic><topic>Thymus Gland - drug effects</topic><topic>Toxicity: blood</topic><topic>ZDV</topic><topic>Zidovudine</topic><topic>Zidovudine - administration & dosage</topic><topic>Zidovudine - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freund, Yvonne R</creatorcontrib><creatorcontrib>Dousman, Linda</creatorcontrib><creatorcontrib>Riccio, Edward S</creatorcontrib><creatorcontrib>Sato, Barbara</creatorcontrib><creatorcontrib>MacGregor, James T</creatorcontrib><creatorcontrib>Mohagheghpour, Nahid</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freund, Yvonne R</au><au>Dousman, Linda</au><au>Riccio, Edward S</au><au>Sato, Barbara</au><au>MacGregor, James T</au><au>Mohagheghpour, Nahid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohematotoxicity studies with combinations of dapsone and zidovudine</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>1</volume><issue>12</issue><spage>2131</spage><epage>2141</epage><pages>2131-2141</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of
Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (
P<0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was ≥35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (
P<0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>11710542</pmid><doi>10.1016/S1567-5769(01)00138-2</doi><tpages>11</tpages></addata></record> |
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| subjects | AIDS-Related Opportunistic Infections - prevention & control Anemia - chemically induced Animals Anti-HIV Agents - administration & dosage Anti-HIV Agents - toxicity antiparasitic agents antiprotozoal agents Antiprotozoal Agents - administration & dosage Antiprotozoal Agents - toxicity AZT Biological and medical sciences Bone Marrow - drug effects Combination therapy Concanavalin A - pharmacology Dapsone Dapsone - administration & dosage Dapsone - analogs & derivatives Dapsone - blood Dapsone - toxicity DDS Dose-Response Relationship, Drug Drug Interactions Drug toxicity and drugs side effects treatment Female Hematotoxicity Leukopenia - chemically induced Lymph Nodes - drug effects Lymphocyte Activation - drug effects Medical sciences Methemoglobinemia - chemically induced Mice Mice, Inbred BALB C Neutropenia - chemically induced Pharmacology. Drug treatments Pneumocystis carinii Pneumonia, Pneumocystis - prevention & control Thrombocytosis - chemically induced Thymus Gland - drug effects Toxicity: blood ZDV Zidovudine Zidovudine - administration & dosage Zidovudine - toxicity |
| title | Immunohematotoxicity studies with combinations of dapsone and zidovudine |
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