In vitro genotoxicity of the West African anti-malarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine
Cryptolepine (CLP), the major alkaloid of the West African anti-malarial herbal Cryptolepis sanguinolenta (Periplocaceae) is a DNA intercalator that exhibits potent toxicity to a variety of mammalian cells in vitro. We have hypothesized that the DNA intercalating properties of cryptolepine could tri...
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| Veröffentlicht in: | Toxicology (Amsterdam) 2005-03, Vol.208 (1), p.141-147 |
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| creator | Ansah, Charles Khan, Ayesha Gooderham, Nigel J. |
| description | Cryptolepine (CLP), the major alkaloid of the West African anti-malarial herbal
Cryptolepis sanguinolenta (Periplocaceae) is a DNA intercalator that exhibits potent toxicity to a variety of mammalian cells in vitro. We have hypothesized that the DNA intercalating properties of cryptolepine could trigger genetic damage in mammalian cells. The objective of the present study was therefore to assess the ability of both cryptolepine (CLP) and the traditional anti-malarial formulation, the aqueous extract from the roots (CSE) to induce mutation at the
hprt locus and micronuclei (MN) formation in V79, a Chinese hamster fibroblast cell line commonly used in genetic toxicity studies. CSE at a high concentration (50
μg/ml) induced an apparent significant ten fold increase in mutant frequency compared to vehicle control (mean of 38 versus 4 mutant clones/10
6 surviving cells) but, this concentration of CSE was very toxic ( |
| doi_str_mv | 10.1016/j.tox.2004.11.026 |
| format | Article |
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Cryptolepis sanguinolenta (Periplocaceae) is a DNA intercalator that exhibits potent toxicity to a variety of mammalian cells in vitro. We have hypothesized that the DNA intercalating properties of cryptolepine could trigger genetic damage in mammalian cells. The objective of the present study was therefore to assess the ability of both cryptolepine (CLP) and the traditional anti-malarial formulation, the aqueous extract from the roots (CSE) to induce mutation at the
hprt locus and micronuclei (MN) formation in V79, a Chinese hamster fibroblast cell line commonly used in genetic toxicity studies. CSE at a high concentration (50
μg/ml) induced an apparent significant ten fold increase in mutant frequency compared to vehicle control (mean of 38 versus 4 mutant clones/10
6 surviving cells) but, this concentration of CSE was very toxic (<15% cell survival). CLP did not appear to be mutagenic in the dosage range used (up to 2.5
μM, equivalent to 1.1
μg/ml). However, after 24
h treatment of V79 cells both CSE and CLP induced a dose-dependent increase in micronuclei of 4.15% and 6.43% (25
μg/ml CSE and 2.5
μM, equivalent to 1.1
μg/ml CLP, respectively) compared to 0.36% in vehicle control. These results show that treatment of mammalian cells with CSE and CLP can lead to DNA damage and we suggest that the routine use of CSE and the potential use of CLP derivatives in malaria chemotherapy could carry a genotoxic risk.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2004.11.026</identifier><identifier>PMID: 15664441</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Africa ; Alkaloids - administration & dosage ; Alkaloids - toxicity ; Animals ; Antimalarials - administration & dosage ; Antimalarials - toxicity ; Biological and medical sciences ; Cell Line ; Cell Survival ; Cricetinae ; Cryptolepine ; Cryptolepis - toxicity ; Cryptolepis sanguinolenta ; DNA Damage ; Dose-Response Relationship, Drug ; Hprt mutation ; Indole Alkaloids ; Indoles - administration & dosage ; Indoles - toxicity ; Intercalating Agents - toxicity ; Medical sciences ; Medicine, Traditional ; Micronuclei ; Mutagenicity Tests ; Plant Extracts - administration & dosage ; Plant Extracts - toxicity ; Plant Roots - toxicity ; Quinolines - administration & dosage ; Quinolines - toxicity ; Toxicology</subject><ispartof>Toxicology (Amsterdam), 2005-03, Vol.208 (1), p.141-147</ispartof><rights>2004 Elsevier Ireland Ltd</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-86f743436469569c4497ac85493aae7296d1c3fe01cab53cc8e02282eda9f4b83</citedby><cites>FETCH-LOGICAL-c478t-86f743436469569c4497ac85493aae7296d1c3fe01cab53cc8e02282eda9f4b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tox.2004.11.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16461014$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15664441$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ansah, Charles</creatorcontrib><creatorcontrib>Khan, Ayesha</creatorcontrib><creatorcontrib>Gooderham, Nigel J.</creatorcontrib><title>In vitro genotoxicity of the West African anti-malarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Cryptolepine (CLP), the major alkaloid of the West African anti-malarial herbal
Cryptolepis sanguinolenta (Periplocaceae) is a DNA intercalator that exhibits potent toxicity to a variety of mammalian cells in vitro. We have hypothesized that the DNA intercalating properties of cryptolepine could trigger genetic damage in mammalian cells. The objective of the present study was therefore to assess the ability of both cryptolepine (CLP) and the traditional anti-malarial formulation, the aqueous extract from the roots (CSE) to induce mutation at the
hprt locus and micronuclei (MN) formation in V79, a Chinese hamster fibroblast cell line commonly used in genetic toxicity studies. CSE at a high concentration (50
μg/ml) induced an apparent significant ten fold increase in mutant frequency compared to vehicle control (mean of 38 versus 4 mutant clones/10
6 surviving cells) but, this concentration of CSE was very toxic (<15% cell survival). CLP did not appear to be mutagenic in the dosage range used (up to 2.5
μM, equivalent to 1.1
μg/ml). However, after 24
h treatment of V79 cells both CSE and CLP induced a dose-dependent increase in micronuclei of 4.15% and 6.43% (25
μg/ml CSE and 2.5
μM, equivalent to 1.1
μg/ml CLP, respectively) compared to 0.36% in vehicle control. These results show that treatment of mammalian cells with CSE and CLP can lead to DNA damage and we suggest that the routine use of CSE and the potential use of CLP derivatives in malaria chemotherapy could carry a genotoxic risk.</description><subject>Africa</subject><subject>Alkaloids - administration & dosage</subject><subject>Alkaloids - toxicity</subject><subject>Animals</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - toxicity</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Survival</subject><subject>Cricetinae</subject><subject>Cryptolepine</subject><subject>Cryptolepis - toxicity</subject><subject>Cryptolepis sanguinolenta</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hprt mutation</subject><subject>Indole Alkaloids</subject><subject>Indoles - administration & dosage</subject><subject>Indoles - toxicity</subject><subject>Intercalating Agents - toxicity</subject><subject>Medical sciences</subject><subject>Medicine, Traditional</subject><subject>Micronuclei</subject><subject>Mutagenicity Tests</subject><subject>Plant Extracts - administration & dosage</subject><subject>Plant Extracts - toxicity</subject><subject>Plant Roots - toxicity</subject><subject>Quinolines - administration & dosage</subject><subject>Quinolines - toxicity</subject><subject>Toxicology</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFrFDEUx4Modlv9AF4kF73NmEwymQyeylJtoeBF0Vt4m3nTZs0ka5ItLvjhTdnF3jw9Hvz-f977EfKGs5Yzrj5s2xJ_tx1jsuW8ZZ16RlZcD2MjuO6fkxUTjDVSix9n5DznLWOsE1K9JGe8V0pKyVfkz02gD66kSO8wxFrnrCsHGmda7pF-x1zo5ZychUAhFNcs4CE58PQe06aOdTrsSvS4c5lmCHd7F-oWClR8oq5kusA2Jgr-J_joJmr_BQK-Ii9m8Blfn-YF-fbp6uv6urn98vlmfXnbWDno0mg1D1JIoaQaezVaKccBrO7lKABw6EY1cStmZNzCphfWamRdpzucYJzlRosL8v7Yu0vx177-ZBaXLXoPAeM-Gz4MSig-VpAfQZtizglns0tugXQwnJlH5WZrqiPzqNxwbqrymnl7Kt9vFpyeEifHFXh3AiBb8HOCYF1-4upbtVpW7uORw6riwWEy2ToMFieX0BYzRfefM_4CwgChAg</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>Ansah, Charles</creator><creator>Khan, Ayesha</creator><creator>Gooderham, Nigel J.</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</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>7U7</scope><scope>C1K</scope></search><sort><creationdate>20050301</creationdate><title>In vitro genotoxicity of the West African anti-malarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine</title><author>Ansah, Charles ; Khan, Ayesha ; Gooderham, Nigel J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-86f743436469569c4497ac85493aae7296d1c3fe01cab53cc8e02282eda9f4b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Africa</topic><topic>Alkaloids - administration & dosage</topic><topic>Alkaloids - toxicity</topic><topic>Animals</topic><topic>Antimalarials - administration & dosage</topic><topic>Antimalarials - toxicity</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Survival</topic><topic>Cricetinae</topic><topic>Cryptolepine</topic><topic>Cryptolepis - toxicity</topic><topic>Cryptolepis sanguinolenta</topic><topic>DNA Damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hprt mutation</topic><topic>Indole Alkaloids</topic><topic>Indoles - administration & dosage</topic><topic>Indoles - toxicity</topic><topic>Intercalating Agents - toxicity</topic><topic>Medical sciences</topic><topic>Medicine, Traditional</topic><topic>Micronuclei</topic><topic>Mutagenicity Tests</topic><topic>Plant Extracts - administration & dosage</topic><topic>Plant Extracts - toxicity</topic><topic>Plant Roots - toxicity</topic><topic>Quinolines - administration & dosage</topic><topic>Quinolines - toxicity</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ansah, Charles</creatorcontrib><creatorcontrib>Khan, Ayesha</creatorcontrib><creatorcontrib>Gooderham, Nigel J.</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ansah, Charles</au><au>Khan, Ayesha</au><au>Gooderham, Nigel J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro genotoxicity of the West African anti-malarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>208</volume><issue>1</issue><spage>141</spage><epage>147</epage><pages>141-147</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>Cryptolepine (CLP), the major alkaloid of the West African anti-malarial herbal
Cryptolepis sanguinolenta (Periplocaceae) is a DNA intercalator that exhibits potent toxicity to a variety of mammalian cells in vitro. We have hypothesized that the DNA intercalating properties of cryptolepine could trigger genetic damage in mammalian cells. The objective of the present study was therefore to assess the ability of both cryptolepine (CLP) and the traditional anti-malarial formulation, the aqueous extract from the roots (CSE) to induce mutation at the
hprt locus and micronuclei (MN) formation in V79, a Chinese hamster fibroblast cell line commonly used in genetic toxicity studies. CSE at a high concentration (50
μg/ml) induced an apparent significant ten fold increase in mutant frequency compared to vehicle control (mean of 38 versus 4 mutant clones/10
6 surviving cells) but, this concentration of CSE was very toxic (<15% cell survival). CLP did not appear to be mutagenic in the dosage range used (up to 2.5
μM, equivalent to 1.1
μg/ml). However, after 24
h treatment of V79 cells both CSE and CLP induced a dose-dependent increase in micronuclei of 4.15% and 6.43% (25
μg/ml CSE and 2.5
μM, equivalent to 1.1
μg/ml CLP, respectively) compared to 0.36% in vehicle control. These results show that treatment of mammalian cells with CSE and CLP can lead to DNA damage and we suggest that the routine use of CSE and the potential use of CLP derivatives in malaria chemotherapy could carry a genotoxic risk.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>15664441</pmid><doi>10.1016/j.tox.2004.11.026</doi><tpages>7</tpages></addata></record> |
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| issn | 0300-483X 1879-3185 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Africa Alkaloids - administration & dosage Alkaloids - toxicity Animals Antimalarials - administration & dosage Antimalarials - toxicity Biological and medical sciences Cell Line Cell Survival Cricetinae Cryptolepine Cryptolepis - toxicity Cryptolepis sanguinolenta DNA Damage Dose-Response Relationship, Drug Hprt mutation Indole Alkaloids Indoles - administration & dosage Indoles - toxicity Intercalating Agents - toxicity Medical sciences Medicine, Traditional Micronuclei Mutagenicity Tests Plant Extracts - administration & dosage Plant Extracts - toxicity Plant Roots - toxicity Quinolines - administration & dosage Quinolines - toxicity Toxicology |
| title | In vitro genotoxicity of the West African anti-malarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine |
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