A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss
Both the antioxidant, n-l-acetyl cysteine (L-NAC) and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intrap...
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| Veröffentlicht in: | Noise & health 2005-10, Vol.7 (29), p.24-30 |
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| creator | Bielefeld, Eric C Hynes, Sarah Pryznosch, David Liu, Jianzhong Coleman, John Km Henderson, Donald |
| description | Both the antioxidant, n-l-acetyl cysteine (L-NAC) and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to either of the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration. |
| doi_str_mv | 10.4103/1463-1741.31875 |
| format | Article |
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To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to either of the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.</description><identifier>ISSN: 1463-1741</identifier><identifier>EISSN: 1998-4030</identifier><identifier>DOI: 10.4103/1463-1741.31875</identifier><identifier>PMID: 17478966</identifier><language>eng</language><publisher>India: Medknow Publications and Media Pvt. 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Ltd.</rights><rights>Copyright Medknow Publications Oct 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-77b06020d2ddb62fb8a5a7f92950834644b9f2338f1a35296c226965119cdff33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27913,27914</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17478966$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bielefeld, Eric C</creatorcontrib><creatorcontrib>Hynes, Sarah</creatorcontrib><creatorcontrib>Pryznosch, David</creatorcontrib><creatorcontrib>Liu, Jianzhong</creatorcontrib><creatorcontrib>Coleman, John Km</creatorcontrib><creatorcontrib>Henderson, Donald</creatorcontrib><title>A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss</title><title>Noise & health</title><addtitle>Noise Health</addtitle><description>Both the antioxidant, n-l-acetyl cysteine (L-NAC) and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to either of the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.</description><subject>Acetylcysteine - administration & dosage</subject><subject>Acetylcysteine - pharmacology</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Auditory Threshold - drug effects</subject><subject>Chinchilla</subject><subject>Deafness, Noise induced</subject><subject>Disease Models, Animal</subject><subject>Dosage and administration</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Electrodes</subject><subject>Environmental Exposure - adverse effects</subject><subject>Evoked Potentials, Auditory - drug effects</subject><subject>Free radicals</subject><subject>Glutathione - administration & dosage</subject><subject>Glutathione - pharmacology</subject><subject>Hearing loss</subject><subject>Hearing Loss, Noise-Induced - drug therapy</subject><subject>Hearing Loss, Noise-Induced - prevention & control</subject><subject>Hearing protection</subject><subject>Inferior Colliculi - physiology</subject><subject>Injections, Intraperitoneal</subject><subject>Kinases</subject><subject>Noise</subject><subject>Noise - adverse effects</subject><subject>Pharmaceutical research</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Reactive Oxygen Species - adverse effects</subject><subject>Side effects</subject><subject>src-Family Kinases - administration & dosage</subject><subject>src-Family Kinases - antagonists & inhibitors</subject><subject>src-Family Kinases - pharmacology</subject><subject>Studies</subject><subject>Time Factors</subject><issn>1463-1741</issn><issn>1998-4030</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkk1rFTEUhgdRbK2u3UlQ6G5u8zGTmSwvxVaxoGBdh0w-7qTMJNckU-gf8fd6xntFK5JFwjnPezh5eavqNcGbhmB2QRrOatI1ZMNI37VPqlMiRF83mOGn8P7dPale5HyHMW4Ipc-rE6h1veD8tPqxRTrOe5V8jgFFh8po0T7FYnXx9xZZ5-CV105-yMXOXiNlZh98LkkVfxCpVVLvpqWoMkLNIpOWHVLBQOtr0vWX20_Ih9EPvsSE1E75kAsK0Wdb-2AWbQ0aLWwRdmiKOb-snjk1ZfvqeJ9V367e315-qG8-X3-83N7UmnFe6q4bMMcUG2rMwKkbetWqzgkqWtyzhjfNIBxlrHdEsZYKrinlgreECG2cY-ysOj_Mhf2_LzYXOfus7TSpYOOSJRFtK3pCAXz7D3gXlxRgN0kx6zpC2hV6d4B2arLSBxfBI71OlFvCW1iK8xaozX8oOGZ1F8xzHuqPBOd_CcCmqYw5gtngdH4MXhxAncDDZJ3cJz-r9CAJlmte5JoIuSZC_soLKN4cv7UMszV_-GNA2E97Zbkh</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Bielefeld, Eric C</creator><creator>Hynes, Sarah</creator><creator>Pryznosch, David</creator><creator>Liu, Jianzhong</creator><creator>Coleman, John Km</creator><creator>Henderson, Donald</creator><general>Medknow Publications and Media Pvt. 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administration & dosage</topic><topic>Acetylcysteine - pharmacology</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Auditory Threshold - drug effects</topic><topic>Chinchilla</topic><topic>Deafness, Noise induced</topic><topic>Disease Models, Animal</topic><topic>Dosage and administration</topic><topic>Drug dosages</topic><topic>Drug therapy</topic><topic>Electrodes</topic><topic>Environmental Exposure - adverse effects</topic><topic>Evoked Potentials, Auditory - drug effects</topic><topic>Free radicals</topic><topic>Glutathione - administration & dosage</topic><topic>Glutathione - pharmacology</topic><topic>Hearing loss</topic><topic>Hearing Loss, Noise-Induced - drug therapy</topic><topic>Hearing Loss, Noise-Induced - prevention & control</topic><topic>Hearing protection</topic><topic>Inferior Colliculi - physiology</topic><topic>Injections, Intraperitoneal</topic><topic>Kinases</topic><topic>Noise</topic><topic>Noise - adverse effects</topic><topic>Pharmaceutical research</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Reactive Oxygen Species - adverse effects</topic><topic>Side effects</topic><topic>src-Family Kinases - administration & dosage</topic><topic>src-Family Kinases - antagonists & inhibitors</topic><topic>src-Family Kinases - pharmacology</topic><topic>Studies</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bielefeld, Eric C</creatorcontrib><creatorcontrib>Hynes, Sarah</creatorcontrib><creatorcontrib>Pryznosch, David</creatorcontrib><creatorcontrib>Liu, Jianzhong</creatorcontrib><creatorcontrib>Coleman, John Km</creatorcontrib><creatorcontrib>Henderson, Donald</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Pollution Abstracts</collection><collection>Safety Science and Risk</collection><jtitle>Noise & health</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bielefeld, Eric C</au><au>Hynes, Sarah</au><au>Pryznosch, David</au><au>Liu, Jianzhong</au><au>Coleman, John Km</au><au>Henderson, Donald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss</atitle><jtitle>Noise & health</jtitle><addtitle>Noise Health</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>7</volume><issue>29</issue><spage>24</spage><epage>30</epage><pages>24-30</pages><issn>1463-1741</issn><eissn>1998-4030</eissn><abstract>Both the antioxidant, n-l-acetyl cysteine (L-NAC) and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to either of the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.</abstract><cop>India</cop><pub>Medknow Publications and Media Pvt. Ltd</pub><pmid>17478966</pmid><doi>10.4103/1463-1741.31875</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Noise & health, 2005-10, Vol.7 (29), p.24-30 |
| issn | 1463-1741 1998-4030 |
| language | eng |
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| source | MEDLINE; Medknow Open Access Medical Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acetylcysteine - administration & dosage Acetylcysteine - pharmacology Animals Antioxidants Apoptosis Apoptosis - drug effects Auditory Threshold - drug effects Chinchilla Deafness, Noise induced Disease Models, Animal Dosage and administration Drug dosages Drug therapy Electrodes Environmental Exposure - adverse effects Evoked Potentials, Auditory - drug effects Free radicals Glutathione - administration & dosage Glutathione - pharmacology Hearing loss Hearing Loss, Noise-Induced - drug therapy Hearing Loss, Noise-Induced - prevention & control Hearing protection Inferior Colliculi - physiology Injections, Intraperitoneal Kinases Noise Noise - adverse effects Pharmaceutical research Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - pharmacology Reactive Oxygen Species - adverse effects Side effects src-Family Kinases - administration & dosage src-Family Kinases - antagonists & inhibitors src-Family Kinases - pharmacology Studies Time Factors |
| title | A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss |
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