Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions
Mature articular cartilage is an avascular tissue characterized by a low oxygen environment. In joint disease, acidosis and further reductions in oxygen levels occur, compromising cartilage integrity.This study investigated how acidosis and very low oxygen levels affect components of the cellular re...
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| Veröffentlicht in: | Free radical biology & medicine 2015-09, Vol.86, p.57-64 |
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| creator | Collins, John A. Moots, Robert J. Clegg, Peter D. Milner, Peter I. |
| description | Mature articular cartilage is an avascular tissue characterized by a low oxygen environment. In joint disease, acidosis and further reductions in oxygen levels occur, compromising cartilage integrity.This study investigated how acidosis and very low oxygen levels affect components of the cellular redox system in equine articular chondrocytesand whether the antioxidants resveratrol and N-acetylcysteine could modulate this system. We used articular chondrocytes isolated from nondiseased equine joints and cultured them in a 3-D alginate bead system for 48h in |
| doi_str_mv | 10.1016/j.freeradbiomed.2015.05.008 |
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•Acidity and low oxygen occur in joint disease.•We investigated how acidosis and low oxygen affected the redox system in chondrocytes.•We looked at whether resveratrol and N-acetylcysteine could modulate these changes.•Acidosis and low oxygen significantly altered components of the redox system.•These changes were defended in the presence of antioxidants.</description><identifier>ISSN: 0891-5849</identifier><identifier>EISSN: 1873-4596</identifier><identifier>DOI: 10.1016/j.freeradbiomed.2015.05.008</identifier><identifier>PMID: 25998424</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acetylcysteine - pharmacology ; Acidosis ; Animals ; Antioxidants ; Antioxidants - pharmacology ; Cartilage ; Cartilage, Articular - cytology ; Cell Hypoxia ; Cells, Cultured ; Chondrocytes - drug effects ; Chondrocytes - metabolism ; Glutathione - metabolism ; Glycosaminoglycans - metabolism ; Horses ; Hydrogen-Ion Concentration ; Interleukin-1 - physiology ; Membrane Potential, Mitochondrial ; Original Contribution ; Oxygen ; Redox balance ; Resveratrol ; Stilbenes - pharmacology ; Superoxide Dismutase - metabolism ; Superoxide Dismutase-1</subject><ispartof>Free radical biology & medicine, 2015-09, Vol.86, p.57-64</ispartof><rights>2015 The Authors</rights><rights>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2015 The Authors 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-a1ac1890cf0bf0fd3fda17fcbc0418b0b7968c1edcc96ab5ec862510f8c0feea3</citedby><cites>FETCH-LOGICAL-c491t-a1ac1890cf0bf0fd3fda17fcbc0418b0b7968c1edcc96ab5ec862510f8c0feea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.freeradbiomed.2015.05.008$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25998424$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Collins, John A.</creatorcontrib><creatorcontrib>Moots, Robert J.</creatorcontrib><creatorcontrib>Clegg, Peter D.</creatorcontrib><creatorcontrib>Milner, Peter I.</creatorcontrib><title>Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions</title><title>Free radical biology & medicine</title><addtitle>Free Radic Biol Med</addtitle><description>Mature articular cartilage is an avascular tissue characterized by a low oxygen environment. In joint disease, acidosis and further reductions in oxygen levels occur, compromising cartilage integrity.This study investigated how acidosis and very low oxygen levels affect components of the cellular redox system in equine articular chondrocytesand whether the antioxidants resveratrol and N-acetylcysteine could modulate this system. We used articular chondrocytes isolated from nondiseased equine joints and cultured them in a 3-D alginate bead system for 48h in <1, 2, 5, and 21% O2 at pH 7.2 or 6.2 in the absence or presence of the proinflammatory cytokine, interleukin-1β (10ng/ml).In addition, chondrocytes were cultured with resveratrol (10µM) or N-acetylcysteine (NAC) (2mM).Cell viability, glycosaminoglycan (GAG) release, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), GSH:GSSG ratio, and SOD1 and SOD2 protein expression were measured. Very low levels of oxygen (<1%), acidosis (pH 6.2), and exposure to IL-1β led to reductions in cell viability, increased GAG release, alterations in ΔΨm and ROS levels, and reduced GSH:GSSG ratio. In addition, SOD1 and SOD2 protein expressions were reduced. Both resveratrol and NAC partially restored ΔΨm and ROS levels and prevented GAG release and cell loss and normalized SOD1 and SOD2 protein expression. In particular NAC was highly effective at restoring the GSH:GSSG ratio.These results show that the antioxidants resveratrol and N-acetylcysteine can counteract the redox imbalance in articular chondrocytes induced by low oxygen and acidic conditions.
•Acidity and low oxygen occur in joint disease.•We investigated how acidosis and low oxygen affected the redox system in chondrocytes.•We looked at whether resveratrol and N-acetylcysteine could modulate these changes.•Acidosis and low oxygen significantly altered components of the redox system.•These changes were defended in the presence of antioxidants.</description><subject>Acetylcysteine - pharmacology</subject><subject>Acidosis</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Cartilage</subject><subject>Cartilage, Articular - cytology</subject><subject>Cell Hypoxia</subject><subject>Cells, Cultured</subject><subject>Chondrocytes - drug effects</subject><subject>Chondrocytes - metabolism</subject><subject>Glutathione - metabolism</subject><subject>Glycosaminoglycans - metabolism</subject><subject>Horses</subject><subject>Hydrogen-Ion Concentration</subject><subject>Interleukin-1 - physiology</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Original Contribution</subject><subject>Oxygen</subject><subject>Redox balance</subject><subject>Resveratrol</subject><subject>Stilbenes - pharmacology</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxide Dismutase-1</subject><issn>0891-5849</issn><issn>1873-4596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkVFrFDEUhQdR7Fr9CxLwxZdZb2ZnZhMEQUqtQlEQfQ6Zm5s2y2zSJplt5wf4v5vt1mLfhAsh5LvnhHOq6h2HJQfef9gsbSSK2gwubMksG-DdEsqAeFYtuFiv6raT_fNqAULyuhOtPKpepbQBgLZbiZfVUdNJKdqmXVR_flLaFbEcw8i0N-x7rZHyPOKcMjlPzHk7TuSRWCQTbtmgR72_Oc_oetoTOmaH06gjw8vgTQw4Z0ps8oYi0-iMw3vp4jOzMdywcDtfkGdYYJdd8Ol19cLqMdGbh_O4-v3l9NfJ1_r8x9m3k8_nNbaS51pzjVxIQAuDBWtW1mi-tjggtFwMMKxlL5CTQZS9HjpC0TcdBysQLJFeHVefDrpX01CiQ_I56lFdRbfVcVZBO_X0xbtLdRF2qu36pmn6IvD-QSCG64lSVluXkMYSCYUpKb4GIWTLQRT04wHFGFKKZB9tOKh9kWqjnhSp9kUqKHO__fbfnz7u_m2uAKcHgEpeO0dRJXT7moyLhFmZ4P7L6A5Ptb2f</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Collins, John A.</creator><creator>Moots, Robert J.</creator><creator>Clegg, Peter D.</creator><creator>Milner, Peter I.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150901</creationdate><title>Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions</title><author>Collins, John A. ; Moots, Robert J. ; Clegg, Peter D. ; Milner, Peter I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-a1ac1890cf0bf0fd3fda17fcbc0418b0b7968c1edcc96ab5ec862510f8c0feea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acetylcysteine - pharmacology</topic><topic>Acidosis</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Cartilage</topic><topic>Cartilage, Articular - cytology</topic><topic>Cell Hypoxia</topic><topic>Cells, Cultured</topic><topic>Chondrocytes - drug effects</topic><topic>Chondrocytes - metabolism</topic><topic>Glutathione - metabolism</topic><topic>Glycosaminoglycans - metabolism</topic><topic>Horses</topic><topic>Hydrogen-Ion Concentration</topic><topic>Interleukin-1 - physiology</topic><topic>Membrane Potential, Mitochondrial</topic><topic>Original Contribution</topic><topic>Oxygen</topic><topic>Redox balance</topic><topic>Resveratrol</topic><topic>Stilbenes - pharmacology</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Superoxide Dismutase-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Collins, John A.</creatorcontrib><creatorcontrib>Moots, Robert J.</creatorcontrib><creatorcontrib>Clegg, Peter D.</creatorcontrib><creatorcontrib>Milner, Peter I.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Free radical biology & medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Collins, John A.</au><au>Moots, Robert J.</au><au>Clegg, Peter D.</au><au>Milner, Peter I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions</atitle><jtitle>Free radical biology & medicine</jtitle><addtitle>Free Radic Biol Med</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>86</volume><spage>57</spage><epage>64</epage><pages>57-64</pages><issn>0891-5849</issn><eissn>1873-4596</eissn><abstract>Mature articular cartilage is an avascular tissue characterized by a low oxygen environment. In joint disease, acidosis and further reductions in oxygen levels occur, compromising cartilage integrity.This study investigated how acidosis and very low oxygen levels affect components of the cellular redox system in equine articular chondrocytesand whether the antioxidants resveratrol and N-acetylcysteine could modulate this system. We used articular chondrocytes isolated from nondiseased equine joints and cultured them in a 3-D alginate bead system for 48h in <1, 2, 5, and 21% O2 at pH 7.2 or 6.2 in the absence or presence of the proinflammatory cytokine, interleukin-1β (10ng/ml).In addition, chondrocytes were cultured with resveratrol (10µM) or N-acetylcysteine (NAC) (2mM).Cell viability, glycosaminoglycan (GAG) release, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), GSH:GSSG ratio, and SOD1 and SOD2 protein expression were measured. Very low levels of oxygen (<1%), acidosis (pH 6.2), and exposure to IL-1β led to reductions in cell viability, increased GAG release, alterations in ΔΨm and ROS levels, and reduced GSH:GSSG ratio. In addition, SOD1 and SOD2 protein expressions were reduced. Both resveratrol and NAC partially restored ΔΨm and ROS levels and prevented GAG release and cell loss and normalized SOD1 and SOD2 protein expression. In particular NAC was highly effective at restoring the GSH:GSSG ratio.These results show that the antioxidants resveratrol and N-acetylcysteine can counteract the redox imbalance in articular chondrocytes induced by low oxygen and acidic conditions.
•Acidity and low oxygen occur in joint disease.•We investigated how acidosis and low oxygen affected the redox system in chondrocytes.•We looked at whether resveratrol and N-acetylcysteine could modulate these changes.•Acidosis and low oxygen significantly altered components of the redox system.•These changes were defended in the presence of antioxidants.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25998424</pmid><doi>10.1016/j.freeradbiomed.2015.05.008</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcysteine - pharmacology Acidosis Animals Antioxidants Antioxidants - pharmacology Cartilage Cartilage, Articular - cytology Cell Hypoxia Cells, Cultured Chondrocytes - drug effects Chondrocytes - metabolism Glutathione - metabolism Glycosaminoglycans - metabolism Horses Hydrogen-Ion Concentration Interleukin-1 - physiology Membrane Potential, Mitochondrial Original Contribution Oxygen Redox balance Resveratrol Stilbenes - pharmacology Superoxide Dismutase - metabolism Superoxide Dismutase-1 |
| title | Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions |
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