Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology
A number of studies have demonstrated a protective effect associated with N-acetyl-l-cysteine (NAC) against toxic chemical exposure. However, the impact of long-term oral dosing on tissue pathology has not been determined. In this study, the authors assessed the impact of long-term oral NAC administ...
Gespeichert in:
| Veröffentlicht in: | International journal of toxicology 2004-07, Vol.23 (4), p.239-247 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 247 |
|---|---|
| container_issue | 4 |
| container_start_page | 239 |
| container_title | International journal of toxicology |
| container_volume | 23 |
| creator | Arfsten, Darryl P. Johnson, Eric W. Thitoff, Angie R. Jung, Anne E. Wilfong, Erin R. Lohrke, Scott M. Bausman, Tim A. Eggers, Jeffrey S. Bobb, Andrew J. |
| description | A number of studies have demonstrated a protective effect associated with
N-acetyl-l-cysteine (NAC) against toxic chemical
exposure. However, the impact of long-term oral dosing on tissue pathology has not
been determined. In this study, the authors assessed the impact of long-term oral NAC
administration on organ histopathology and tissue glutathione (GSH) and total
glutathione-S-transferase (GST) activity levels in Sprague-Dawley
(SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed
daily by oral gavage with deionized H2O (negative controls) or NAC
solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h
after treatment on study day 30. There were no significant differences in final body
weights or weekly average weight gain between treatment groups. Serum alanine
amino-transferase (ALT) activities were significantly elevated (p
≤.05) in NAC-treated animals compared to controls when measured on study day 30.
Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen,
thymus, and lungs revealed no lesions associated with NAC administration. When
measured on study day 30, total GST activity for kidney and skin from NAC-treated
animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations
from NAC-treated animals were increased 24% to 81% as compared with negative
controls. Further studies are needed to determine if the observed increase in tissue
GSH concentration and GST activity provide a degree of chemoprotection against dermal
and systemic chemical toxicants. |
| doi_str_mv | 10.1080/10915810490502041 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_18055018</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1080_10915810490502041</sage_id><sourcerecordid>18055018</sourcerecordid><originalsourceid>FETCH-LOGICAL-c367t-a570400d1317a87a832d5fadf7fe1bd9e588eb585e9a222e7e0e6c398b35d7663</originalsourceid><addsrcrecordid>eNp9kM1Lw0AQxRdRrFb_AC-yJ29bZ5JudnOU1o9CseIX3sI2maQpSbZmE0r-e6MteBCEgRmG33vwHmMXCCMEDdcIIUqNMA5BggdjPGAn_c8TWo0_Dn9uFD2gB-zUuTUABEriMRug9BVioE_Y-6zcmLjhNuU-iKnp-KI2BZ9al1cZ3-bNij8KE1PTFaIQcecayivituIvm9pkLfWabUEdfzYNf1p1LreFzbozdpSawtH5fg_Z293t6-RBzBf3s8nNXMR-oBphpIIxQII-KqP78b1EpiZJVUq4TEKSWtNSakmh8TyPFAEFsR_qpS8TFQT-kF3tfDe1_WzJNVGZu5iKwlRkWxehBikBdQ_iDoxr61xNabSp89LUXYQQfZcZ_Smz11zuzdtlScmvYt9eD4x2gDMZRWvb1lUf9h_HL8QzesE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18055018</pqid></control><display><type>article</type><title>Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology</title><source>MEDLINE</source><source>SAGE Complete</source><source>Alma/SFX Local Collection</source><creator>Arfsten, Darryl P. ; Johnson, Eric W. ; Thitoff, Angie R. ; Jung, Anne E. ; Wilfong, Erin R. ; Lohrke, Scott M. ; Bausman, Tim A. ; Eggers, Jeffrey S. ; Bobb, Andrew J.</creator><creatorcontrib>Arfsten, Darryl P. ; Johnson, Eric W. ; Thitoff, Angie R. ; Jung, Anne E. ; Wilfong, Erin R. ; Lohrke, Scott M. ; Bausman, Tim A. ; Eggers, Jeffrey S. ; Bobb, Andrew J.</creatorcontrib><description>A number of studies have demonstrated a protective effect associated with
N-acetyl-l-cysteine (NAC) against toxic chemical
exposure. However, the impact of long-term oral dosing on tissue pathology has not
been determined. In this study, the authors assessed the impact of long-term oral NAC
administration on organ histopathology and tissue glutathione (GSH) and total
glutathione-S-transferase (GST) activity levels in Sprague-Dawley
(SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed
daily by oral gavage with deionized H2O (negative controls) or NAC
solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h
after treatment on study day 30. There were no significant differences in final body
weights or weekly average weight gain between treatment groups. Serum alanine
amino-transferase (ALT) activities were significantly elevated (p
≤.05) in NAC-treated animals compared to controls when measured on study day 30.
Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen,
thymus, and lungs revealed no lesions associated with NAC administration. When
measured on study day 30, total GST activity for kidney and skin from NAC-treated
animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations
from NAC-treated animals were increased 24% to 81% as compared with negative
controls. Further studies are needed to determine if the observed increase in tissue
GSH concentration and GST activity provide a degree of chemoprotection against dermal
and systemic chemical toxicants.</description><identifier>ISSN: 1091-5818</identifier><identifier>EISSN: 1092-874X</identifier><identifier>DOI: 10.1080/10915810490502041</identifier><identifier>PMID: 15371168</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Acetylcysteine - administration & dosage ; Acetylcysteine - toxicity ; Alanine Transaminase - blood ; Animals ; Antidotes - administration & dosage ; Antidotes - toxicity ; Dose-Response Relationship, Drug ; Female ; Glutathione - metabolism ; Glutathione Transferase - metabolism ; Kidney - drug effects ; Kidney - enzymology ; Male ; Rats ; Rats, Sprague-Dawley ; Skin - drug effects ; Skin - enzymology ; Toxicity Tests</subject><ispartof>International journal of toxicology, 2004-07, Vol.23 (4), p.239-247</ispartof><rights>Copyright © American College of Toxicology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c367t-a570400d1317a87a832d5fadf7fe1bd9e588eb585e9a222e7e0e6c398b35d7663</citedby><cites>FETCH-LOGICAL-c367t-a570400d1317a87a832d5fadf7fe1bd9e588eb585e9a222e7e0e6c398b35d7663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1080/10915810490502041$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1080/10915810490502041$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15371168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arfsten, Darryl P.</creatorcontrib><creatorcontrib>Johnson, Eric W.</creatorcontrib><creatorcontrib>Thitoff, Angie R.</creatorcontrib><creatorcontrib>Jung, Anne E.</creatorcontrib><creatorcontrib>Wilfong, Erin R.</creatorcontrib><creatorcontrib>Lohrke, Scott M.</creatorcontrib><creatorcontrib>Bausman, Tim A.</creatorcontrib><creatorcontrib>Eggers, Jeffrey S.</creatorcontrib><creatorcontrib>Bobb, Andrew J.</creatorcontrib><title>Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology</title><title>International journal of toxicology</title><addtitle>Int J Toxicol</addtitle><description>A number of studies have demonstrated a protective effect associated with
N-acetyl-l-cysteine (NAC) against toxic chemical
exposure. However, the impact of long-term oral dosing on tissue pathology has not
been determined. In this study, the authors assessed the impact of long-term oral NAC
administration on organ histopathology and tissue glutathione (GSH) and total
glutathione-S-transferase (GST) activity levels in Sprague-Dawley
(SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed
daily by oral gavage with deionized H2O (negative controls) or NAC
solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h
after treatment on study day 30. There were no significant differences in final body
weights or weekly average weight gain between treatment groups. Serum alanine
amino-transferase (ALT) activities were significantly elevated (p
≤.05) in NAC-treated animals compared to controls when measured on study day 30.
Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen,
thymus, and lungs revealed no lesions associated with NAC administration. When
measured on study day 30, total GST activity for kidney and skin from NAC-treated
animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations
from NAC-treated animals were increased 24% to 81% as compared with negative
controls. Further studies are needed to determine if the observed increase in tissue
GSH concentration and GST activity provide a degree of chemoprotection against dermal
and systemic chemical toxicants.</description><subject>Acetylcysteine - administration & dosage</subject><subject>Acetylcysteine - toxicity</subject><subject>Alanine Transaminase - blood</subject><subject>Animals</subject><subject>Antidotes - administration & dosage</subject><subject>Antidotes - toxicity</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Glutathione - metabolism</subject><subject>Glutathione Transferase - metabolism</subject><subject>Kidney - drug effects</subject><subject>Kidney - enzymology</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Skin - drug effects</subject><subject>Skin - enzymology</subject><subject>Toxicity Tests</subject><issn>1091-5818</issn><issn>1092-874X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1Lw0AQxRdRrFb_AC-yJ29bZ5JudnOU1o9CseIX3sI2maQpSbZmE0r-e6MteBCEgRmG33vwHmMXCCMEDdcIIUqNMA5BggdjPGAn_c8TWo0_Dn9uFD2gB-zUuTUABEriMRug9BVioE_Y-6zcmLjhNuU-iKnp-KI2BZ9al1cZ3-bNij8KE1PTFaIQcecayivituIvm9pkLfWabUEdfzYNf1p1LreFzbozdpSawtH5fg_Z293t6-RBzBf3s8nNXMR-oBphpIIxQII-KqP78b1EpiZJVUq4TEKSWtNSakmh8TyPFAEFsR_qpS8TFQT-kF3tfDe1_WzJNVGZu5iKwlRkWxehBikBdQ_iDoxr61xNabSp89LUXYQQfZcZ_Smz11zuzdtlScmvYt9eD4x2gDMZRWvb1lUf9h_HL8QzesE</recordid><startdate>200407</startdate><enddate>200407</enddate><creator>Arfsten, Darryl P.</creator><creator>Johnson, Eric W.</creator><creator>Thitoff, Angie R.</creator><creator>Jung, Anne E.</creator><creator>Wilfong, Erin R.</creator><creator>Lohrke, Scott M.</creator><creator>Bausman, Tim A.</creator><creator>Eggers, Jeffrey S.</creator><creator>Bobb, Andrew J.</creator><general>SAGE Publications</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>200407</creationdate><title>Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology</title><author>Arfsten, Darryl P. ; Johnson, Eric W. ; Thitoff, Angie R. ; Jung, Anne E. ; Wilfong, Erin R. ; Lohrke, Scott M. ; Bausman, Tim A. ; Eggers, Jeffrey S. ; Bobb, Andrew J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-a570400d1317a87a832d5fadf7fe1bd9e588eb585e9a222e7e0e6c398b35d7663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Acetylcysteine - administration & dosage</topic><topic>Acetylcysteine - toxicity</topic><topic>Alanine Transaminase - blood</topic><topic>Animals</topic><topic>Antidotes - administration & dosage</topic><topic>Antidotes - toxicity</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Transferase - metabolism</topic><topic>Kidney - drug effects</topic><topic>Kidney - enzymology</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Skin - drug effects</topic><topic>Skin - enzymology</topic><topic>Toxicity Tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arfsten, Darryl P.</creatorcontrib><creatorcontrib>Johnson, Eric W.</creatorcontrib><creatorcontrib>Thitoff, Angie R.</creatorcontrib><creatorcontrib>Jung, Anne E.</creatorcontrib><creatorcontrib>Wilfong, Erin R.</creatorcontrib><creatorcontrib>Lohrke, Scott M.</creatorcontrib><creatorcontrib>Bausman, Tim A.</creatorcontrib><creatorcontrib>Eggers, Jeffrey S.</creatorcontrib><creatorcontrib>Bobb, Andrew J.</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>International journal of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arfsten, Darryl P.</au><au>Johnson, Eric W.</au><au>Thitoff, Angie R.</au><au>Jung, Anne E.</au><au>Wilfong, Erin R.</au><au>Lohrke, Scott M.</au><au>Bausman, Tim A.</au><au>Eggers, Jeffrey S.</au><au>Bobb, Andrew J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology</atitle><jtitle>International journal of toxicology</jtitle><addtitle>Int J Toxicol</addtitle><date>2004-07</date><risdate>2004</risdate><volume>23</volume><issue>4</issue><spage>239</spage><epage>247</epage><pages>239-247</pages><issn>1091-5818</issn><eissn>1092-874X</eissn><abstract>A number of studies have demonstrated a protective effect associated with
N-acetyl-l-cysteine (NAC) against toxic chemical
exposure. However, the impact of long-term oral dosing on tissue pathology has not
been determined. In this study, the authors assessed the impact of long-term oral NAC
administration on organ histopathology and tissue glutathione (GSH) and total
glutathione-S-transferase (GST) activity levels in Sprague-Dawley
(SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed
daily by oral gavage with deionized H2O (negative controls) or NAC
solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h
after treatment on study day 30. There were no significant differences in final body
weights or weekly average weight gain between treatment groups. Serum alanine
amino-transferase (ALT) activities were significantly elevated (p
≤.05) in NAC-treated animals compared to controls when measured on study day 30.
Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen,
thymus, and lungs revealed no lesions associated with NAC administration. When
measured on study day 30, total GST activity for kidney and skin from NAC-treated
animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations
from NAC-treated animals were increased 24% to 81% as compared with negative
controls. Further studies are needed to determine if the observed increase in tissue
GSH concentration and GST activity provide a degree of chemoprotection against dermal
and systemic chemical toxicants.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>15371168</pmid><doi>10.1080/10915810490502041</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1091-5818 |
| ispartof | International journal of toxicology, 2004-07, Vol.23 (4), p.239-247 |
| issn | 1091-5818 1092-874X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_18055018 |
| source | MEDLINE; SAGE Complete; Alma/SFX Local Collection |
| subjects | Acetylcysteine - administration & dosage Acetylcysteine - toxicity Alanine Transaminase - blood Animals Antidotes - administration & dosage Antidotes - toxicity Dose-Response Relationship, Drug Female Glutathione - metabolism Glutathione Transferase - metabolism Kidney - drug effects Kidney - enzymology Male Rats Rats, Sprague-Dawley Skin - drug effects Skin - enzymology Toxicity Tests |
| title | Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T00%3A51%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impact%20of%2030-Day%20Oral%20Dosing%20with%20N-acetyl-l-cysteine%20on%20Sprague-Dawley%20Rat%20Physiology&rft.jtitle=International%20journal%20of%20toxicology&rft.au=Arfsten,%20Darryl%20P.&rft.date=2004-07&rft.volume=23&rft.issue=4&rft.spage=239&rft.epage=247&rft.pages=239-247&rft.issn=1091-5818&rft.eissn=1092-874X&rft_id=info:doi/10.1080/10915810490502041&rft_dat=%3Cproquest_cross%3E18055018%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18055018&rft_id=info:pmid/15371168&rft_sage_id=10.1080_10915810490502041&rfr_iscdi=true |