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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Veröffentlicht in:Food and chemical toxicology 2011-01, Vol.49 (1), p.173-178
Hauptverfasser: Khan, Mahaboob S., Halagowder, Devaraj, Devaraj, S Niranjali
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creator Khan, Mahaboob S.
Halagowder, Devaraj
Devaraj, S Niranjali
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.
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Drug treatments</subject><subject>Precancerous Conditions - chemically induced</subject><subject>Precancerous Conditions - metabolism</subject><subject>Precancerous Conditions - prevention &amp; 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 &amp; 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 &amp; 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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