The protective role of zinc and N-acetylcysteine in modulating zidovudine induced hematopoietic toxicity
The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine bone marrow progenitor cells (BMPC, 1 × 10 6) were exposed to various concentrations (0.1–50 μM) of AZT in the presence and absence of zin...
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| Veröffentlicht in: | Life sciences (1973) 1996, Vol.59 (16), p.1323-1329 |
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| creator | Gogu, Sudhir R. Agrawal, Krishna C. |
| description | The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine bone marrow progenitor cells (BMPC, 1 × 10
6) were exposed to various concentrations (0.1–50 μM) of AZT in the presence and absence of zinc acetate (100 μM) or NAC (100 μM). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The 1C
50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 μM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 μM) in the CFU-GM assay whereas in the presence of NAC, the IC
50 values were increased by 2- and 4-fold, respectively. To delineate the mechanism of significant protection of BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a 31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT mRNA levels in BMPC These results suggest that zinc and NAC dietary supplementation can be conveniently used to reduce AZT-induced bone marrow toxicity. |
| doi_str_mv | 10.1016/0024-3205(96)00457-2 |
| format | Article |
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6) were exposed to various concentrations (0.1–50 μM) of AZT in the presence and absence of zinc acetate (100 μM) or NAC (100 μM). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The 1C
50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 μM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 μM) in the CFU-GM assay whereas in the presence of NAC, the IC
50 values were increased by 2- and 4-fold, respectively. To delineate the mechanism of significant protection of BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a 31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT mRNA levels in BMPC These results suggest that zinc and NAC dietary supplementation can be conveniently used to reduce AZT-induced bone marrow toxicity.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/0024-3205(96)00457-2</identifier><identifier>PMID: 8876661</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Acetylcysteine - pharmacology ; Acetylcysteine - therapeutic use ; Animals ; Antidotes - pharmacology ; Antidotes - therapeutic use ; Bone Marrow - drug effects ; Cell Survival - drug effects ; Female ; hematopoiesis ; Hematopoietic Stem Cells - cytology ; metallothionein ; Mice ; N-acetylcysteine ; Zidovudine - adverse effects ; zidovudine toxicity ; zinc ; Zinc - pharmacology ; Zinc - therapeutic use</subject><ispartof>Life sciences (1973), 1996, Vol.59 (16), p.1323-1329</ispartof><rights>1996</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-141228ccc80ddba0851ac18b998503aba976d5d219838d3aef9ff4f2fa7931e43</citedby><cites>FETCH-LOGICAL-c388t-141228ccc80ddba0851ac18b998503aba976d5d219838d3aef9ff4f2fa7931e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0024-3205(96)00457-2$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8876661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gogu, Sudhir R.</creatorcontrib><creatorcontrib>Agrawal, Krishna C.</creatorcontrib><title>The protective role of zinc and N-acetylcysteine in modulating zidovudine induced hematopoietic toxicity</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine bone marrow progenitor cells (BMPC, 1 × 10
6) were exposed to various concentrations (0.1–50 μM) of AZT in the presence and absence of zinc acetate (100 μM) or NAC (100 μM). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The 1C
50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 μM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 μM) in the CFU-GM assay whereas in the presence of NAC, the IC
50 values were increased by 2- and 4-fold, respectively. To delineate the mechanism of significant protection of BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a 31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT mRNA levels in BMPC These results suggest that zinc and NAC dietary supplementation can be conveniently used to reduce AZT-induced bone marrow toxicity.</description><subject>Acetylcysteine - pharmacology</subject><subject>Acetylcysteine - therapeutic use</subject><subject>Animals</subject><subject>Antidotes - pharmacology</subject><subject>Antidotes - therapeutic use</subject><subject>Bone Marrow - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Female</subject><subject>hematopoiesis</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>metallothionein</subject><subject>Mice</subject><subject>N-acetylcysteine</subject><subject>Zidovudine - adverse effects</subject><subject>zidovudine toxicity</subject><subject>zinc</subject><subject>Zinc - pharmacology</subject><subject>Zinc - therapeutic use</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAUhYMoOj7-gUJWootq0rR5bAQZfIHoRtchk9w6kbYZm3Rw_PVmmMGlq8vlnHMv50PolJIrSii_JqSsClaS-kLxS0KqWhTlDppQKVRBOKO7aPJnOUCHMX4SQupasH20L6XgnNMJmr_NAS-GkMAmvwQ8hBZwaPCP7y02vcMvhbGQVq1dxQS-B-x73AU3tib5_iP7XFiObiO40YLDc-hMCovgIXmLU_j21qfVMdprTBvhZDuP0Pv93dv0sXh-fXia3j4XlkmZClrRspTWWkmcmxkia2oslTOlZE2YmRkluKtdSZVk0jEDjWqaqikbIxSjULEjdL65m0t9jRCT7ny00LamhzBGTWvBKy5ENlYbox1CjAM0ejH4zgwrTYleA9ZrenpNT6v1kgHrMsfOtvfHWQfuL7QlmvWbjQ655NLDoKP10GcwfsiMtQv-_we_SjuMFQ</recordid><startdate>1996</startdate><enddate>1996</enddate><creator>Gogu, Sudhir R.</creator><creator>Agrawal, Krishna C.</creator><general>Elsevier Inc</general><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>7U7</scope><scope>C1K</scope></search><sort><creationdate>1996</creationdate><title>The protective role of zinc and N-acetylcysteine in modulating zidovudine induced hematopoietic toxicity</title><author>Gogu, Sudhir R. ; Agrawal, Krishna C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-141228ccc80ddba0851ac18b998503aba976d5d219838d3aef9ff4f2fa7931e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Acetylcysteine - pharmacology</topic><topic>Acetylcysteine - therapeutic use</topic><topic>Animals</topic><topic>Antidotes - pharmacology</topic><topic>Antidotes - therapeutic use</topic><topic>Bone Marrow - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Female</topic><topic>hematopoiesis</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>metallothionein</topic><topic>Mice</topic><topic>N-acetylcysteine</topic><topic>Zidovudine - adverse effects</topic><topic>zidovudine toxicity</topic><topic>zinc</topic><topic>Zinc - pharmacology</topic><topic>Zinc - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gogu, Sudhir R.</creatorcontrib><creatorcontrib>Agrawal, Krishna C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gogu, Sudhir R.</au><au>Agrawal, Krishna C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The protective role of zinc and N-acetylcysteine in modulating zidovudine induced hematopoietic toxicity</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>1996</date><risdate>1996</risdate><volume>59</volume><issue>16</issue><spage>1323</spage><epage>1329</epage><pages>1323-1329</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>The role of zinc and N-acetylcysteine (NAC) has been investigated in protecting the hematopoietic progenitor cells from zidovudine (AZT)-induced toxicity. Murine bone marrow progenitor cells (BMPC, 1 × 10
6) were exposed to various concentrations (0.1–50 μM) of AZT in the presence and absence of zinc acetate (100 μM) or NAC (100 μM). The cell survival was determined by the colony forming assays of erythroid (CFU-E) and granulocytic (CFU-GM) lineage. The 1C
50 values of AZT in the presence of zinc were increased approximately 3-fold (from 3.0 to 9.5 μM) in the CFU-E assay and 7-fold (from 4.3 to 28.8 μM) in the CFU-GM assay whereas in the presence of NAC, the IC
50 values were increased by 2- and 4-fold, respectively. To delineate the mechanism of significant protection of BMPC by zinc, the mRNA levels of metallothionein (MT) were monitored by using a 31-mer cDNA probe. Zinc produced a concentration-dependent increase in the MT mRNA levels in BMPC These results suggest that zinc and NAC dietary supplementation can be conveniently used to reduce AZT-induced bone marrow toxicity.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>8876661</pmid><doi>10.1016/0024-3205(96)00457-2</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Life sciences (1973), 1996, Vol.59 (16), p.1323-1329 |
| issn | 0024-3205 1879-0631 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Acetylcysteine - pharmacology Acetylcysteine - therapeutic use Animals Antidotes - pharmacology Antidotes - therapeutic use Bone Marrow - drug effects Cell Survival - drug effects Female hematopoiesis Hematopoietic Stem Cells - cytology metallothionein Mice N-acetylcysteine Zidovudine - adverse effects zidovudine toxicity zinc Zinc - pharmacology Zinc - therapeutic use |
| title | The protective role of zinc and N-acetylcysteine in modulating zidovudine induced hematopoietic toxicity |
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