Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-Nitrosodiethylamine in rats
The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200mg/kg bodyweight) interspersed by 2weeks with or without an oral...
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description | The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200mg/kg bodyweight) interspersed by 2weeks with or without an oral dose of dimethoxy flavone (DMF 100mg/kg bodyweight), 2weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN. |
doi_str_mv | 10.1016/j.fct.2010.10.013 |
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Male Wistar rats were administered three intraperitoneal injections of DEN (200mg/kg bodyweight) interspersed by 2weeks with or without an oral dose of dimethoxy flavone (DMF 100mg/kg bodyweight), 2weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2010.10.013</identifier><identifier>PMID: 20955752</identifier><identifier>CODEN: FCTOD7</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Antineoplastic agents ; Apoptosis ; Base Sequence ; Biological and medical sciences ; Carcinogenesis, carcinogens and anticarcinogens ; Carcinogens - toxicity ; Cell Cycle Proteins - genetics ; Chemical agents ; Chemotherapy ; Dietary flavones ; Diethylnitrosamine ; Diethylnitrosamine - toxicity ; DNA Primers ; DNA Repair - genetics ; Flavonoids - pharmacology ; Glutathione Transferase - metabolism ; Immunohistochemistry ; Liver Neoplasms, Experimental - chemically induced ; Liver Neoplasms, Experimental - metabolism ; Liver Neoplasms, Experimental - prevention & control ; Medical sciences ; Methylated chrysin ; Methylation ; Pharmacology. Drug treatments ; Precancerous Conditions - chemically induced ; Precancerous Conditions - metabolism ; Precancerous Conditions - prevention & control ; Preneoplastic lesions ; Proliferating Cell Nuclear Antigen - metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Tumors</subject><ispartof>Food and chemical toxicology, 2011-01, Vol.49 (1), p.173-178</ispartof><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-b00f5f587df8f44ddede2aa912da35ddf37a21147935e8bba20e87d17602ee0d3</citedby><cites>FETCH-LOGICAL-c446t-b00f5f587df8f44ddede2aa912da35ddf37a21147935e8bba20e87d17602ee0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fct.2010.10.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23734496$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20955752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Mahaboob S.</creatorcontrib><creatorcontrib>Halagowder, Devaraj</creatorcontrib><creatorcontrib>Devaraj, S Niranjali</creatorcontrib><title>Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-Nitrosodiethylamine in rats</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200mg/kg bodyweight) interspersed by 2weeks with or without an oral dose of dimethoxy flavone (DMF 100mg/kg bodyweight), 2weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Carcinogens - toxicity</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Chemical agents</subject><subject>Chemotherapy</subject><subject>Dietary flavones</subject><subject>Diethylnitrosamine</subject><subject>Diethylnitrosamine - toxicity</subject><subject>DNA Primers</subject><subject>DNA Repair - genetics</subject><subject>Flavonoids - pharmacology</subject><subject>Glutathione Transferase - metabolism</subject><subject>Immunohistochemistry</subject><subject>Liver Neoplasms, Experimental - chemically induced</subject><subject>Liver Neoplasms, Experimental - metabolism</subject><subject>Liver Neoplasms, Experimental - prevention & control</subject><subject>Medical sciences</subject><subject>Methylated chrysin</subject><subject>Methylation</subject><subject>Pharmacology. Drug treatments</subject><subject>Precancerous Conditions - chemically induced</subject><subject>Precancerous Conditions - metabolism</subject><subject>Precancerous Conditions - prevention & control</subject><subject>Preneoplastic lesions</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>Rats</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tumors</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2O1DAQhS0EYpqBA7BB3iA2k8aOkzgRq9GIP2kYNrCOHLusdsuJg8tpkYNwX9zTDeyAleXSV69e1SPkOWdbznjzer-1Om1Ldv_fMi4ekA1vpSgaUfOHZMNK2RZNx-sL8gRxzxiTXDaPyUXJurqWdbkhPz5B2q1eJTBU7-KKbrqiiho35nr4vlLr1SFMcEVnFZNT3q8Ul3mOgAhI0w6ogQP4MI8wJRos9e4AkWZggjB7hclp6gFdmJC6ySw6TxpWelfcuRQDBuNODkY3QQZoVAmfkkdWeYRn5_eSfH339svNh-L28_uPN9e3ha6qJhUDY7a2dSuNbW1VGQMGSqU6XholamOskKrkvJKdqKEdBlUyyHC-ASsBmBGX5NVJd47h2wKY-tGhBu9VNr9g3zZMtKztmv8isyxn_yazo67tuMwkP5E63wEj2H6OblRx7TnrjwH3-z4H3B8DPpZywLnnxVl9GUYwvzt-JZqBl2dAoVbeRjVph384IUVV3S_05sRBvu_BQexRO5hyOi5CHmqC-4uNnzrtxtE</recordid><startdate>201101</startdate><enddate>201101</enddate><creator>Khan, Mahaboob S.</creator><creator>Halagowder, Devaraj</creator><creator>Devaraj, S Niranjali</creator><general>Elsevier Ltd</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><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>201101</creationdate><title>Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-Nitrosodiethylamine in rats</title><author>Khan, Mahaboob S. ; Halagowder, Devaraj ; Devaraj, S Niranjali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-b00f5f587df8f44ddede2aa912da35ddf37a21147935e8bba20e87d17602ee0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Carcinogens - toxicity</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Chemical agents</topic><topic>Chemotherapy</topic><topic>Dietary flavones</topic><topic>Diethylnitrosamine</topic><topic>Diethylnitrosamine - toxicity</topic><topic>DNA Primers</topic><topic>DNA Repair - genetics</topic><topic>Flavonoids - pharmacology</topic><topic>Glutathione Transferase - metabolism</topic><topic>Immunohistochemistry</topic><topic>Liver Neoplasms, Experimental - chemically induced</topic><topic>Liver Neoplasms, Experimental - metabolism</topic><topic>Liver Neoplasms, Experimental - prevention & control</topic><topic>Medical sciences</topic><topic>Methylated chrysin</topic><topic>Methylation</topic><topic>Pharmacology. Drug treatments</topic><topic>Precancerous Conditions - chemically induced</topic><topic>Precancerous Conditions - metabolism</topic><topic>Precancerous Conditions - prevention & control</topic><topic>Preneoplastic lesions</topic><topic>Proliferating Cell Nuclear Antigen - metabolism</topic><topic>Rats</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, Mahaboob S.</creatorcontrib><creatorcontrib>Halagowder, Devaraj</creatorcontrib><creatorcontrib>Devaraj, S Niranjali</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><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Mahaboob S.</au><au>Halagowder, Devaraj</au><au>Devaraj, S Niranjali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-Nitrosodiethylamine in rats</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2011-01</date><risdate>2011</risdate><volume>49</volume><issue>1</issue><spage>173</spage><epage>178</epage><pages>173-178</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><coden>FCTOD7</coden><abstract>The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200mg/kg bodyweight) interspersed by 2weeks with or without an oral dose of dimethoxy flavone (DMF 100mg/kg bodyweight), 2weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>20955752</pmid><doi>10.1016/j.fct.2010.10.013</doi><tpages>6</tpages></addata></record> |
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subjects | Animals Antineoplastic agents Apoptosis Base Sequence Biological and medical sciences Carcinogenesis, carcinogens and anticarcinogens Carcinogens - toxicity Cell Cycle Proteins - genetics Chemical agents Chemotherapy Dietary flavones Diethylnitrosamine Diethylnitrosamine - toxicity DNA Primers DNA Repair - genetics Flavonoids - pharmacology Glutathione Transferase - metabolism Immunohistochemistry Liver Neoplasms, Experimental - chemically induced Liver Neoplasms, Experimental - metabolism Liver Neoplasms, Experimental - prevention & control Medical sciences Methylated chrysin Methylation Pharmacology. Drug treatments Precancerous Conditions - chemically induced Precancerous Conditions - metabolism Precancerous Conditions - prevention & control Preneoplastic lesions Proliferating Cell Nuclear Antigen - metabolism Rats Reverse Transcriptase Polymerase Chain Reaction Tumors |
title | Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-Nitrosodiethylamine in rats |
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