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Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug
Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharm...
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| Published in: | Immunopharmacology and immunotoxicology 2015-11, Vol.37 (6), p.535-540 |
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| container_title | Immunopharmacology and immunotoxicology |
| container_volume | 37 |
| creator | Fattahi, Mohammad Javad Abdollahi, Mohammad Agha Mohammadi, Asghar Rastkari, Noushin Khorasani, Reza Ahmadi, Hossein Tofighi Zavareh, Farzaneh Sedaghat, Reza Tabrizian, Nakisa Mirshafiey, Abbas |
| description | Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.
Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.
Materials and methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.
Results: The results of acute toxicity indicated that the LD
50
of β-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.
Conclusions: Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals. |
| doi_str_mv | 10.3109/08923973.2015.1113296 |
| format | article |
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Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.
Materials and methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.
Results: The results of acute toxicity indicated that the LD
50
of β-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.
Conclusions: Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals.</description><identifier>ISSN: 0892-3973</identifier><identifier>EISSN: 1532-2513</identifier><identifier>DOI: 10.3109/08923973.2015.1113296</identifier><identifier>PMID: 26584020</identifier><language>eng</language><publisher>England: Informa Healthcare</publisher><subject>Acute toxicity ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - toxicity ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical - methods ; Hexuronic Acids - toxicity ; M2000 ; Male ; Mice ; non-steroidal anti-inflammatory drugs ; Rats ; Rats, Wistar ; subchronic toxicity ; Toxicity Tests, Acute - methods ; Toxicity Tests, Subchronic - methods ; β-D-mannuronic acid</subject><ispartof>Immunopharmacology and immunotoxicology, 2015-11, Vol.37 (6), p.535-540</ispartof><rights>2015 Taylor & Francis 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-a64666e2bab3f7716068b3ed328d47f3a008bfa62fd779ee7db74ab16b51d0aa3</citedby><cites>FETCH-LOGICAL-c399t-a64666e2bab3f7716068b3ed328d47f3a008bfa62fd779ee7db74ab16b51d0aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26584020$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fattahi, Mohammad Javad</creatorcontrib><creatorcontrib>Abdollahi, Mohammad</creatorcontrib><creatorcontrib>Agha Mohammadi, Asghar</creatorcontrib><creatorcontrib>Rastkari, Noushin</creatorcontrib><creatorcontrib>Khorasani, Reza</creatorcontrib><creatorcontrib>Ahmadi, Hossein</creatorcontrib><creatorcontrib>Tofighi Zavareh, Farzaneh</creatorcontrib><creatorcontrib>Sedaghat, Reza</creatorcontrib><creatorcontrib>Tabrizian, Nakisa</creatorcontrib><creatorcontrib>Mirshafiey, Abbas</creatorcontrib><title>Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug</title><title>Immunopharmacology and immunotoxicology</title><addtitle>Immunopharmacol Immunotoxicol</addtitle><description>Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.
Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.
Materials and methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.
Results: The results of acute toxicity indicated that the LD
50
of β-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.
Conclusions: Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals.</description><subject>Acute toxicity</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - toxicity</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Hexuronic Acids - toxicity</subject><subject>M2000</subject><subject>Male</subject><subject>Mice</subject><subject>non-steroidal anti-inflammatory drugs</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>subchronic toxicity</subject><subject>Toxicity Tests, Acute - methods</subject><subject>Toxicity Tests, Subchronic - methods</subject><subject>β-D-mannuronic acid</subject><issn>0892-3973</issn><issn>1532-2513</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kMFO3DAURa2Kqgy0n1CUJSw8fbYndrwrQrQggWDRrt2X2K6MEpvaidD8Fh_CNzXRDCxZvcU7917pEPKVwVow0N-g0VxoJdYcWL1mjAmu5QeyYrXglNdMHJDVwtAFOiRHpTwAMK2g_kQOuaybDXBYkT_32XV9iKHDvsJSXCmDi2OVfPXyTC0dMMYpp_lfYRdsdXrLAeBsRiusYoq0jC6nYJd0HAMN0fc4DDimvK1snv5-Jh899sV92d9j8vvH5a-LK3pz9_P64vyGdkLrkaLcSCkdb7EVXikmQTatcFbwxm6UFwjQtB4l91Yp7Zyyrdpgy2RbMwuI4pic7nofc_o3uTKaIZTO9T1Gl6ZimJJNrYQWbEbrHdrlVEp23jzmMGDeGgZmkWte5ZpFrtnLnXMn-4mpHZx9S73anIHvO2C2kPKATyn31oy47VP2GWMXytL_3sZ_gBSJSQ</recordid><startdate>20151102</startdate><enddate>20151102</enddate><creator>Fattahi, Mohammad Javad</creator><creator>Abdollahi, Mohammad</creator><creator>Agha Mohammadi, Asghar</creator><creator>Rastkari, Noushin</creator><creator>Khorasani, Reza</creator><creator>Ahmadi, Hossein</creator><creator>Tofighi Zavareh, Farzaneh</creator><creator>Sedaghat, Reza</creator><creator>Tabrizian, Nakisa</creator><creator>Mirshafiey, Abbas</creator><general>Informa Healthcare</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20151102</creationdate><title>Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug</title><author>Fattahi, Mohammad Javad ; Abdollahi, Mohammad ; Agha Mohammadi, Asghar ; Rastkari, Noushin ; Khorasani, Reza ; Ahmadi, Hossein ; Tofighi Zavareh, Farzaneh ; Sedaghat, Reza ; Tabrizian, Nakisa ; Mirshafiey, Abbas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-a64666e2bab3f7716068b3ed328d47f3a008bfa62fd779ee7db74ab16b51d0aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acute toxicity</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - toxicity</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Hexuronic Acids - toxicity</topic><topic>M2000</topic><topic>Male</topic><topic>Mice</topic><topic>non-steroidal anti-inflammatory drugs</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>subchronic toxicity</topic><topic>Toxicity Tests, Acute - methods</topic><topic>Toxicity Tests, Subchronic - methods</topic><topic>β-D-mannuronic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fattahi, Mohammad Javad</creatorcontrib><creatorcontrib>Abdollahi, Mohammad</creatorcontrib><creatorcontrib>Agha Mohammadi, Asghar</creatorcontrib><creatorcontrib>Rastkari, Noushin</creatorcontrib><creatorcontrib>Khorasani, Reza</creatorcontrib><creatorcontrib>Ahmadi, Hossein</creatorcontrib><creatorcontrib>Tofighi Zavareh, Farzaneh</creatorcontrib><creatorcontrib>Sedaghat, Reza</creatorcontrib><creatorcontrib>Tabrizian, Nakisa</creatorcontrib><creatorcontrib>Mirshafiey, Abbas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Immunopharmacology and immunotoxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fattahi, Mohammad Javad</au><au>Abdollahi, Mohammad</au><au>Agha Mohammadi, Asghar</au><au>Rastkari, Noushin</au><au>Khorasani, Reza</au><au>Ahmadi, Hossein</au><au>Tofighi Zavareh, Farzaneh</au><au>Sedaghat, Reza</au><au>Tabrizian, Nakisa</au><au>Mirshafiey, Abbas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug</atitle><jtitle>Immunopharmacology and immunotoxicology</jtitle><addtitle>Immunopharmacol Immunotoxicol</addtitle><date>2015-11-02</date><risdate>2015</risdate><volume>37</volume><issue>6</issue><spage>535</spage><epage>540</epage><pages>535-540</pages><issn>0892-3973</issn><eissn>1532-2513</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.
Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.
Materials and methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.
Results: The results of acute toxicity indicated that the LD
50
of β-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.
Conclusions: Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals.</abstract><cop>England</cop><pub>Informa Healthcare</pub><pmid>26584020</pmid><doi>10.3109/08923973.2015.1113296</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0892-3973 |
| ispartof | Immunopharmacology and immunotoxicology, 2015-11, Vol.37 (6), p.535-540 |
| issn | 0892-3973 1532-2513 |
| language | eng |
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| source | Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list) |
| subjects | Acute toxicity Animals Anti-Inflammatory Agents, Non-Steroidal - toxicity Dose-Response Relationship, Drug Drug Evaluation, Preclinical - methods Hexuronic Acids - toxicity M2000 Male Mice non-steroidal anti-inflammatory drugs Rats Rats, Wistar subchronic toxicity Toxicity Tests, Acute - methods Toxicity Tests, Subchronic - methods β-D-mannuronic acid |
| title | Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug |
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