Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration
During sepsis, brain damage is associated with oxidative stress due to overproduction of reactive oxygen species (ROS). Although there are recent reports about the benefits of statins in experimental sepsis and endotoxemia in peripheral organs, little is known about their effects in the CNS. Here, w...
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| Veröffentlicht in: | Molecular neurobiology 2017-11, Vol.54 (9), p.7008-7018 |
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| creator | Catalão, Carlos Henrique Rocha Santos-Júnior, Nilton Nascimento da Costa, Luís Henrique Angenendt Souza, Anderson Oliveira Alberici, Luciane Carla Rocha, Maria José Alves |
| description | During sepsis, brain damage is associated with oxidative stress due to overproduction of reactive oxygen species (ROS). Although there are recent reports about the benefits of statins in experimental sepsis and endotoxemia in peripheral organs, little is known about their effects in the CNS. Here, we investigated the antioxidant properties of simvastatin and its possible neuroprotective role during experimental sepsis. Male Wistar rats (250–300 g) were submitted to cecal ligation and puncture (CLP,
n
= 34) or remained as non-manipulated (naive,
n
= 34). Both groups were treated by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline. The animals submitted to CLP were treated 4 days before and 48 h after surgery. One animal group was decapitated and the blood and brain were collected to quantify plasma levels of cytokines and assess astrogliosis and apoptosis in the prefrontal cortex and hippocampus. Another group was perfused with PBS (0.01 M), and the same brain structures were dissected to analyze oxidative damage. The CLP rats treated with simvastatin showed a reduction in nitric oxide (
P
|
| doi_str_mv | 10.1007/s12035-016-0218-3 |
| format | Article |
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n
= 34) or remained as non-manipulated (naive,
n
= 34). Both groups were treated by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline. The animals submitted to CLP were treated 4 days before and 48 h after surgery. One animal group was decapitated and the blood and brain were collected to quantify plasma levels of cytokines and assess astrogliosis and apoptosis in the prefrontal cortex and hippocampus. Another group was perfused with PBS (0.01 M), and the same brain structures were dissected to analyze oxidative damage. The CLP rats treated with simvastatin showed a reduction in nitric oxide (
P
< 0.05), IL1-β (
P
< 0.001), IL-6 (
P
< 0.01), and TBARS levels (
P
< 0.001) and an increase in catalase activity (
P
< 0.01), citrate synthase enzyme (
P
< 0.05), and normalized GSH/GSSG ratio. In addition, the histopathological analysis showed a reduction (
P
< 0.001) in reactive astrocytes and caspase 3-positive apoptotic cells. The results suggest a possible neuroprotective effect of simvastatin in structures responsible for spatial learning and memory and indicate the need for behavioral studies evaluating the impact on cognitive damage, as frequently seen in patients surviving sepsis.]]></description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-016-0218-3</identifier><identifier>PMID: 27796742</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Astrocytes ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain - pathology ; Brain injury ; Caspase ; Caspase 3 - metabolism ; Caspase-3 ; Catalase ; Cecum ; Cecum - pathology ; Cell Biology ; Central nervous system ; Citrate (si)-Synthase - metabolism ; Citrate synthase ; Cognitive ability ; Cytokines - blood ; Drug therapy ; Endotoxemia ; Glial Fibrillary Acidic Protein - metabolism ; Gliosis ; Hippocampus - enzymology ; Impact damage ; Interleukin 1 ; Interleukin 6 ; Ligation ; Male ; Memory ; Models, Biological ; Neurobiology ; Neurology ; Neuroprotection ; Neurosciences ; Nitrates - blood ; Nitric oxide ; Organs ; Oxidative stress ; Oxidative Stress - drug effects ; Plasma levels ; Prefrontal cortex ; Prefrontal Cortex - enzymology ; Punctures ; Rats ; Rats, Wistar ; Reactive oxygen species ; Rodents ; Sepsis ; Sepsis - blood ; Sepsis - pathology ; Simvastatin ; Simvastatin - administration & dosage ; Simvastatin - pharmacology ; Spatial discrimination learning ; Statins ; Surgery ; Thiobarbituric Acid Reactive Substances - metabolism</subject><ispartof>Molecular neurobiology, 2017-11, Vol.54 (9), p.7008-7018</ispartof><rights>Springer Science+Business Media New York 2016</rights><rights>Molecular Neurobiology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-db28cece9b709edc2cb1a64c9b889fc03c4ae060b5219c6f6ba84fa1dbfb44463</citedby><cites>FETCH-LOGICAL-c372t-db28cece9b709edc2cb1a64c9b889fc03c4ae060b5219c6f6ba84fa1dbfb44463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-016-0218-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-016-0218-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27796742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Catalão, Carlos Henrique Rocha</creatorcontrib><creatorcontrib>Santos-Júnior, Nilton Nascimento</creatorcontrib><creatorcontrib>da Costa, Luís Henrique Angenendt</creatorcontrib><creatorcontrib>Souza, Anderson Oliveira</creatorcontrib><creatorcontrib>Alberici, Luciane Carla</creatorcontrib><creatorcontrib>Rocha, Maria José Alves</creatorcontrib><title>Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description><![CDATA[During sepsis, brain damage is associated with oxidative stress due to overproduction of reactive oxygen species (ROS). Although there are recent reports about the benefits of statins in experimental sepsis and endotoxemia in peripheral organs, little is known about their effects in the CNS. Here, we investigated the antioxidant properties of simvastatin and its possible neuroprotective role during experimental sepsis. Male Wistar rats (250–300 g) were submitted to cecal ligation and puncture (CLP,
n
= 34) or remained as non-manipulated (naive,
n
= 34). Both groups were treated by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline. The animals submitted to CLP were treated 4 days before and 48 h after surgery. One animal group was decapitated and the blood and brain were collected to quantify plasma levels of cytokines and assess astrogliosis and apoptosis in the prefrontal cortex and hippocampus. Another group was perfused with PBS (0.01 M), and the same brain structures were dissected to analyze oxidative damage. The CLP rats treated with simvastatin showed a reduction in nitric oxide (
P
< 0.05), IL1-β (
P
< 0.001), IL-6 (
P
< 0.01), and TBARS levels (
P
< 0.001) and an increase in catalase activity (
P
< 0.01), citrate synthase enzyme (
P
< 0.05), and normalized GSH/GSSG ratio. In addition, the histopathological analysis showed a reduction (
P
< 0.001) in reactive astrocytes and caspase 3-positive apoptotic cells. The results suggest a possible neuroprotective effect of simvastatin in structures responsible for spatial learning and memory and indicate the need for behavioral studies evaluating the impact on cognitive damage, as frequently seen in patients surviving sepsis.]]></description><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Astrocytes</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain - pathology</subject><subject>Brain injury</subject><subject>Caspase</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase-3</subject><subject>Catalase</subject><subject>Cecum</subject><subject>Cecum - pathology</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>Citrate (si)-Synthase - metabolism</subject><subject>Citrate synthase</subject><subject>Cognitive ability</subject><subject>Cytokines - blood</subject><subject>Drug therapy</subject><subject>Endotoxemia</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Gliosis</subject><subject>Hippocampus - enzymology</subject><subject>Impact damage</subject><subject>Interleukin 1</subject><subject>Interleukin 6</subject><subject>Ligation</subject><subject>Male</subject><subject>Memory</subject><subject>Models, Biological</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Nitrates - blood</subject><subject>Nitric oxide</subject><subject>Organs</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Plasma levels</subject><subject>Prefrontal cortex</subject><subject>Prefrontal Cortex - enzymology</subject><subject>Punctures</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reactive oxygen species</subject><subject>Rodents</subject><subject>Sepsis</subject><subject>Sepsis - blood</subject><subject>Sepsis - pathology</subject><subject>Simvastatin</subject><subject>Simvastatin - administration & dosage</subject><subject>Simvastatin - pharmacology</subject><subject>Spatial discrimination learning</subject><subject>Statins</subject><subject>Surgery</subject><subject>Thiobarbituric Acid Reactive Substances - metabolism</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kE1rFTEUhoMo9lr9AW4k4MbNaL4mH8trW9tCoYurSwlJ5oyk3MmMSaa0_95cbhURXB0OPO97Dg9Cbyn5SAlRnwplhPcdobIjjOqOP0Mb2vemo1Sz52hDtOGdkkKfoFel3BHCGCXqJTphShmpBNug75-ziwnfPsTB1XgPeFczlILP1xzTD3zxsECOE6Tq9ngHS4kFXxe8rRXS6ioM2D_iXZzuXaktn_B2mGKKpea2zek1ejG6fYE3T_MUffty8fXsqru5vbw-2950gStWu8EzHSCA8YoYGAILnjopgvFamzEQHoQDIonvGTVBjtI7LUZHBz96IYTkp-jDsXfJ888VSrVTLAH2e5dgXoulmgtj-p6Qhr7_B72b15zad5YaIZTk0tBG0SMV8lxKhtEuTYPLj5YSe3Bvj-5tc28P7i1vmXdPzaufYPiT-C27AewIlOUgF_Jfp__b-gvnLJAb</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Catalão, Carlos Henrique Rocha</creator><creator>Santos-Júnior, Nilton Nascimento</creator><creator>da Costa, Luís Henrique Angenendt</creator><creator>Souza, Anderson Oliveira</creator><creator>Alberici, Luciane Carla</creator><creator>Rocha, Maria José Alves</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20171101</creationdate><title>Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration</title><author>Catalão, Carlos Henrique Rocha ; Santos-Júnior, Nilton Nascimento ; da Costa, Luís Henrique Angenendt ; Souza, Anderson Oliveira ; Alberici, Luciane Carla ; Rocha, Maria José Alves</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-db28cece9b709edc2cb1a64c9b889fc03c4ae060b5219c6f6ba84fa1dbfb44463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Astrocytes</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain - pathology</topic><topic>Brain injury</topic><topic>Caspase</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase-3</topic><topic>Catalase</topic><topic>Cecum</topic><topic>Cecum - pathology</topic><topic>Cell Biology</topic><topic>Central nervous system</topic><topic>Citrate (si)-Synthase - metabolism</topic><topic>Citrate synthase</topic><topic>Cognitive ability</topic><topic>Cytokines - blood</topic><topic>Drug therapy</topic><topic>Endotoxemia</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Gliosis</topic><topic>Hippocampus - enzymology</topic><topic>Impact damage</topic><topic>Interleukin 1</topic><topic>Interleukin 6</topic><topic>Ligation</topic><topic>Male</topic><topic>Memory</topic><topic>Models, Biological</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neuroprotection</topic><topic>Neurosciences</topic><topic>Nitrates - blood</topic><topic>Nitric oxide</topic><topic>Organs</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Plasma levels</topic><topic>Prefrontal cortex</topic><topic>Prefrontal Cortex - enzymology</topic><topic>Punctures</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reactive oxygen species</topic><topic>Rodents</topic><topic>Sepsis</topic><topic>Sepsis - blood</topic><topic>Sepsis - pathology</topic><topic>Simvastatin</topic><topic>Simvastatin - administration & dosage</topic><topic>Simvastatin - pharmacology</topic><topic>Spatial discrimination learning</topic><topic>Statins</topic><topic>Surgery</topic><topic>Thiobarbituric Acid Reactive Substances - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Catalão, Carlos Henrique Rocha</creatorcontrib><creatorcontrib>Santos-Júnior, Nilton Nascimento</creatorcontrib><creatorcontrib>da Costa, Luís Henrique Angenendt</creatorcontrib><creatorcontrib>Souza, Anderson Oliveira</creatorcontrib><creatorcontrib>Alberici, Luciane Carla</creatorcontrib><creatorcontrib>Rocha, Maria José Alves</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>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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 China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Catalão, Carlos Henrique Rocha</au><au>Santos-Júnior, Nilton Nascimento</au><au>da Costa, Luís Henrique Angenendt</au><au>Souza, Anderson Oliveira</au><au>Alberici, Luciane Carla</au><au>Rocha, Maria José Alves</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>54</volume><issue>9</issue><spage>7008</spage><epage>7018</epage><pages>7008-7018</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract><![CDATA[During sepsis, brain damage is associated with oxidative stress due to overproduction of reactive oxygen species (ROS). Although there are recent reports about the benefits of statins in experimental sepsis and endotoxemia in peripheral organs, little is known about their effects in the CNS. Here, we investigated the antioxidant properties of simvastatin and its possible neuroprotective role during experimental sepsis. Male Wistar rats (250–300 g) were submitted to cecal ligation and puncture (CLP,
n
= 34) or remained as non-manipulated (naive,
n
= 34). Both groups were treated by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline. The animals submitted to CLP were treated 4 days before and 48 h after surgery. One animal group was decapitated and the blood and brain were collected to quantify plasma levels of cytokines and assess astrogliosis and apoptosis in the prefrontal cortex and hippocampus. Another group was perfused with PBS (0.01 M), and the same brain structures were dissected to analyze oxidative damage. The CLP rats treated with simvastatin showed a reduction in nitric oxide (
P
< 0.05), IL1-β (
P
< 0.001), IL-6 (
P
< 0.01), and TBARS levels (
P
< 0.001) and an increase in catalase activity (
P
< 0.01), citrate synthase enzyme (
P
< 0.05), and normalized GSH/GSSG ratio. In addition, the histopathological analysis showed a reduction (
P
< 0.001) in reactive astrocytes and caspase 3-positive apoptotic cells. The results suggest a possible neuroprotective effect of simvastatin in structures responsible for spatial learning and memory and indicate the need for behavioral studies evaluating the impact on cognitive damage, as frequently seen in patients surviving sepsis.]]></abstract><cop>New York</cop><pub>Springer US</pub><pmid>27796742</pmid><doi>10.1007/s12035-016-0218-3</doi><tpages>11</tpages></addata></record> |
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| ispartof | Molecular neurobiology, 2017-11, Vol.54 (9), p.7008-7018 |
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| subjects | Animals Antioxidants Apoptosis Apoptosis - drug effects Astrocytes Biomedical and Life Sciences Biomedicine Brain Brain - pathology Brain injury Caspase Caspase 3 - metabolism Caspase-3 Catalase Cecum Cecum - pathology Cell Biology Central nervous system Citrate (si)-Synthase - metabolism Citrate synthase Cognitive ability Cytokines - blood Drug therapy Endotoxemia Glial Fibrillary Acidic Protein - metabolism Gliosis Hippocampus - enzymology Impact damage Interleukin 1 Interleukin 6 Ligation Male Memory Models, Biological Neurobiology Neurology Neuroprotection Neurosciences Nitrates - blood Nitric oxide Organs Oxidative stress Oxidative Stress - drug effects Plasma levels Prefrontal cortex Prefrontal Cortex - enzymology Punctures Rats Rats, Wistar Reactive oxygen species Rodents Sepsis Sepsis - blood Sepsis - pathology Simvastatin Simvastatin - administration & dosage Simvastatin - pharmacology Spatial discrimination learning Statins Surgery Thiobarbituric Acid Reactive Substances - metabolism |
| title | Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration |
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