Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice
Metformin is a first-line antidiabetic drug in type 2 diabetes for its hypoglycemic activity, but recently researches also revealed the anti-inflammatory properties of metformin. In the present study, the pharmacological efficiency of metformin in lipopolysaccharide (LPS)-induced hepatic injury in D...
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| Veröffentlicht in: | International immunopharmacology 2012-04, Vol.12 (4), p.682-688 |
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| creator | Yuan, Hongmei Li, Longjiang Zheng, Weiping Wan, Jingyuan Ge, Pu Li, Hongzhong Zhang, Li |
| description | Metformin is a first-line antidiabetic drug in type 2 diabetes for its hypoglycemic activity, but recently researches also revealed the anti-inflammatory properties of metformin. In the present study, the pharmacological efficiency of metformin in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice was investigated. We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections, decreased myeloperoxidase (MPO) activity, reduced malondialdehyde (MDA) content in liver homogenates and increased survival rate of experimental animals. Metformin also markedly reduced hepatic TNF-α mRNA content and blood TNF-α level. Additional experiment showed that metformin significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by decreased caspase activities in liver tissues and reduced number of TUNEL-positive cells in liver sections. Furthermore, therapeutic administration of metformin after LPS/D-Gal challenge also improved the survival rate of experimental animal. These results indicated that the hypoglycemic reagent metformin could also provide therapeutic benefits in endotoxin-induced hepatic injury, suggesting its pharmacological potential in inflammation-base disorders.
► The first-line antidiabetic drug metformin alleviated endotoxic liver injury in mice. ► Metformin reduced TNF-α expression and hepatocyte apoptosis in LPS/D-gal-challenged mice. ► Treatment with metformin improved the survival rate of LPS/D-gal-challenged mice. |
| doi_str_mv | 10.1016/j.intimp.2012.01.015 |
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► The first-line antidiabetic drug metformin alleviated endotoxic liver injury in mice. ► Metformin reduced TNF-α expression and hepatocyte apoptosis in LPS/D-gal-challenged mice. ► Treatment with metformin improved the survival rate of LPS/D-gal-challenged mice.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2012.01.015</identifier><identifier>PMID: 22330083</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>Animals ; Anti-Inflammatory Agents - therapeutic use ; Antidiabetic ; Apoptosis - drug effects ; Biological and medical sciences ; Caspases - metabolism ; Chemical and Drug Induced Liver Injury - drug therapy ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - pathology ; Endotoxin ; Galactosamine ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatitis ; Hypoglycemic Agents - therapeutic use ; Inflammation ; Lipopolysaccharide ; Lipopolysaccharides ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Malondialdehyde - metabolism ; Medical sciences ; Metformin ; Metformin - therapeutic use ; Mice ; Mice, Inbred BALB C ; Other diseases. Semiology ; Pharmacology. Drug treatments ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>International immunopharmacology, 2012-04, Vol.12 (4), p.682-688</ispartof><rights>2012 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-d62738ac67cdd25e374cbca5e93644ed4dae88cfa120ff4ead71662c7aa3ba1f3</citedby><cites>FETCH-LOGICAL-c391t-d62738ac67cdd25e374cbca5e93644ed4dae88cfa120ff4ead71662c7aa3ba1f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2012.01.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25795108$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22330083$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Hongmei</creatorcontrib><creatorcontrib>Li, Longjiang</creatorcontrib><creatorcontrib>Zheng, Weiping</creatorcontrib><creatorcontrib>Wan, Jingyuan</creatorcontrib><creatorcontrib>Ge, Pu</creatorcontrib><creatorcontrib>Li, Hongzhong</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><title>Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>Metformin is a first-line antidiabetic drug in type 2 diabetes for its hypoglycemic activity, but recently researches also revealed the anti-inflammatory properties of metformin. In the present study, the pharmacological efficiency of metformin in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice was investigated. We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections, decreased myeloperoxidase (MPO) activity, reduced malondialdehyde (MDA) content in liver homogenates and increased survival rate of experimental animals. Metformin also markedly reduced hepatic TNF-α mRNA content and blood TNF-α level. Additional experiment showed that metformin significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by decreased caspase activities in liver tissues and reduced number of TUNEL-positive cells in liver sections. Furthermore, therapeutic administration of metformin after LPS/D-Gal challenge also improved the survival rate of experimental animal. These results indicated that the hypoglycemic reagent metformin could also provide therapeutic benefits in endotoxin-induced hepatic injury, suggesting its pharmacological potential in inflammation-base disorders.
► The first-line antidiabetic drug metformin alleviated endotoxic liver injury in mice. ► Metformin reduced TNF-α expression and hepatocyte apoptosis in LPS/D-gal-challenged mice. ► Treatment with metformin improved the survival rate of LPS/D-gal-challenged mice.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Antidiabetic</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Caspases - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - drug therapy</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Endotoxin</subject><subject>Galactosamine</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatitis</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Inflammation</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharides</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Malondialdehyde - metabolism</subject><subject>Medical sciences</subject><subject>Metformin</subject><subject>Metformin - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Other diseases. Semiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEuLFDEQgIMo7jr6D0T6InvqMY_upPsiLIurwoKXXTyGmqQiNXSnxyQ9uP_eLDPqTSioovjqwcfYW8G3ggv9Yb-lWGg-bCUXcstFjf4ZuxSDGVpheP-81r02bW_0eMFe5bznvPY78ZJdSKkU54O6ZN-v6xJPsMNCrvFp_dHMWMKSZooNTBMeCQrmBqNfyvKLYkvRrw59E9apMhBLM9ERU0Nxv6bHmpqZHL5mLwJMGd-c84Y93H66v_nS3n37_PXm-q51ahSl9VoaNYDTxnkve1SmczsHPY5Kdx36zgMOgwsgJA-hQ_BGaC2dAVA7EEFt2NVp7yEtP1fMxc6UHU4TRFzWbEetBjkI3VWyO5EuLTknDPaQaIb0aAW3T0bt3p6M2iejlosafR17dz6w7mb0f4f-KKzA-zMA2cEUEkRH-R_Xm7EXFdywjycOq44jYbLZEcaqkhK6Yv1C___kN1stmKE</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Yuan, Hongmei</creator><creator>Li, Longjiang</creator><creator>Zheng, Weiping</creator><creator>Wan, Jingyuan</creator><creator>Ge, Pu</creator><creator>Li, Hongzhong</creator><creator>Zhang, Li</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</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></search><sort><creationdate>20120401</creationdate><title>Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice</title><author>Yuan, Hongmei ; Li, Longjiang ; Zheng, Weiping ; Wan, Jingyuan ; Ge, Pu ; Li, Hongzhong ; Zhang, Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-d62738ac67cdd25e374cbca5e93644ed4dae88cfa120ff4ead71662c7aa3ba1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Antidiabetic</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Caspases - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - drug therapy</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Endotoxin</topic><topic>Galactosamine</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatitis</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Inflammation</topic><topic>Lipopolysaccharide</topic><topic>Lipopolysaccharides</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Malondialdehyde - metabolism</topic><topic>Medical sciences</topic><topic>Metformin</topic><topic>Metformin - therapeutic use</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Other diseases. Semiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Hongmei</creatorcontrib><creatorcontrib>Li, Longjiang</creatorcontrib><creatorcontrib>Zheng, Weiping</creatorcontrib><creatorcontrib>Wan, Jingyuan</creatorcontrib><creatorcontrib>Ge, Pu</creatorcontrib><creatorcontrib>Li, Hongzhong</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><collection>Pascal-Francis</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><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Hongmei</au><au>Li, Longjiang</au><au>Zheng, Weiping</au><au>Wan, Jingyuan</au><au>Ge, Pu</au><au>Li, Hongzhong</au><au>Zhang, Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>12</volume><issue>4</issue><spage>682</spage><epage>688</epage><pages>682-688</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>Metformin is a first-line antidiabetic drug in type 2 diabetes for its hypoglycemic activity, but recently researches also revealed the anti-inflammatory properties of metformin. In the present study, the pharmacological efficiency of metformin in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice was investigated. We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections, decreased myeloperoxidase (MPO) activity, reduced malondialdehyde (MDA) content in liver homogenates and increased survival rate of experimental animals. Metformin also markedly reduced hepatic TNF-α mRNA content and blood TNF-α level. Additional experiment showed that metformin significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by decreased caspase activities in liver tissues and reduced number of TUNEL-positive cells in liver sections. Furthermore, therapeutic administration of metformin after LPS/D-Gal challenge also improved the survival rate of experimental animal. These results indicated that the hypoglycemic reagent metformin could also provide therapeutic benefits in endotoxin-induced hepatic injury, suggesting its pharmacological potential in inflammation-base disorders.
► The first-line antidiabetic drug metformin alleviated endotoxic liver injury in mice. ► Metformin reduced TNF-α expression and hepatocyte apoptosis in LPS/D-gal-challenged mice. ► Treatment with metformin improved the survival rate of LPS/D-gal-challenged mice.</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>22330083</pmid><doi>10.1016/j.intimp.2012.01.015</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - therapeutic use Antidiabetic Apoptosis - drug effects Biological and medical sciences Caspases - metabolism Chemical and Drug Induced Liver Injury - drug therapy Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - pathology Endotoxin Galactosamine Gastroenterology. Liver. Pancreas. Abdomen Hepatitis Hypoglycemic Agents - therapeutic use Inflammation Lipopolysaccharide Lipopolysaccharides Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Malondialdehyde - metabolism Medical sciences Metformin Metformin - therapeutic use Mice Mice, Inbred BALB C Other diseases. Semiology Pharmacology. Drug treatments Tumor Necrosis Factor-alpha - metabolism |
| title | Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice |
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