Effects of Tacrolimus and Nifedipine, Alone or in Combination, on Gingival Tissues

Background: The aim of this study is to compare gingival changes induced by short‐ and long‐term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug‐induced gingival overgrowth. Method...

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Veröffentlicht in:Journal of periodontology (1970) 2013-11, Vol.84 (11), p.1673-1682
Hauptverfasser: Pamuk, Ferda, Cetinkaya, Burcu Ozkan, Gulbahar, Mustafa Yavuz, Gacar, Ayhan, Cayır Keles, Gonca, Erisgin, Zuleyha, Arik, Nurol
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container_end_page 1682
container_issue 11
container_start_page 1673
container_title Journal of periodontology (1970)
container_volume 84
creator Pamuk, Ferda
Cetinkaya, Burcu Ozkan
Gulbahar, Mustafa Yavuz
Gacar, Ayhan
Cayır Keles, Gonca
Erisgin, Zuleyha
Arik, Nurol
description Background: The aim of this study is to compare gingival changes induced by short‐ and long‐term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug‐induced gingival overgrowth. Methods: Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8‐week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24‐week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry. Results: Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P
doi_str_mv 10.1902/jop.2013.120545
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Methods: Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8‐week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24‐week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry. Results: Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P &lt;0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P &lt;0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P &lt;0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P &lt;0.05). Conclusions: Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug‐induced gingival overgrowth.</description><identifier>ISSN: 0022-3492</identifier><identifier>EISSN: 1943-3670</identifier><identifier>DOI: 10.1902/jop.2013.120545</identifier><identifier>PMID: 23289868</identifier><language>eng</language><publisher>United States: American Academy of Periodontology</publisher><subject>Animals ; Blood Vessels - drug effects ; Calcium Channel Blockers - administration &amp; dosage ; Calcium Channel Blockers - adverse effects ; Calcium Channel Blockers - pharmacology ; Cell Count ; Collagen - drug effects ; Connective Tissue - drug effects ; Connective Tissue - pathology ; Dentistry ; Drug Combinations ; Epithelium - drug effects ; Epithelium - pathology ; Fibroblasts - drug effects ; Fibroblasts - pathology ; Gene Expression Regulation, Enzymologic - drug effects ; Gingiva - drug effects ; Gingiva - pathology ; Gingival overgrowth ; Gingival Overgrowth - chemically induced ; immunohistochemistry ; Immunosuppressive Agents - administration &amp; dosage ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - pharmacology ; Male ; nifedipine ; Nifedipine - administration &amp; dosage ; Nifedipine - adverse effects ; Nifedipine - pharmacology ; PTEN Phosphohydrolase - drug effects ; PTEN Phosphohydrolase - genetics ; PTEN protein ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; tacrolimus ; Tacrolimus - administration &amp; dosage ; Tacrolimus - adverse effects ; Tacrolimus - pharmacology ; Time Factors</subject><ispartof>Journal of periodontology (1970), 2013-11, Vol.84 (11), p.1673-1682</ispartof><rights>2013 American Academy of Periodontology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3433-f9ff7bc4b377993dbc98c8720fd3e63bc89e0f2c74fa0bed6cf04add966bb6a83</citedby><cites>FETCH-LOGICAL-c3433-f9ff7bc4b377993dbc98c8720fd3e63bc89e0f2c74fa0bed6cf04add966bb6a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1902%2Fjop.2013.120545$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1902%2Fjop.2013.120545$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23289868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pamuk, Ferda</creatorcontrib><creatorcontrib>Cetinkaya, Burcu Ozkan</creatorcontrib><creatorcontrib>Gulbahar, Mustafa Yavuz</creatorcontrib><creatorcontrib>Gacar, Ayhan</creatorcontrib><creatorcontrib>Cayır Keles, Gonca</creatorcontrib><creatorcontrib>Erisgin, Zuleyha</creatorcontrib><creatorcontrib>Arik, Nurol</creatorcontrib><title>Effects of Tacrolimus and Nifedipine, Alone or in Combination, on Gingival Tissues</title><title>Journal of periodontology (1970)</title><addtitle>J Periodontol</addtitle><description>Background: The aim of this study is to compare gingival changes induced by short‐ and long‐term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug‐induced gingival overgrowth. Methods: Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8‐week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24‐week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry. Results: Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P &lt;0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P &lt;0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P &lt;0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P &lt;0.05). Conclusions: Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug‐induced gingival overgrowth.</description><subject>Animals</subject><subject>Blood Vessels - drug effects</subject><subject>Calcium Channel Blockers - administration &amp; dosage</subject><subject>Calcium Channel Blockers - adverse effects</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cell Count</subject><subject>Collagen - drug effects</subject><subject>Connective Tissue - drug effects</subject><subject>Connective Tissue - pathology</subject><subject>Dentistry</subject><subject>Drug Combinations</subject><subject>Epithelium - drug effects</subject><subject>Epithelium - pathology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - pathology</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Gingiva - drug effects</subject><subject>Gingiva - pathology</subject><subject>Gingival overgrowth</subject><subject>Gingival Overgrowth - chemically induced</subject><subject>immunohistochemistry</subject><subject>Immunosuppressive Agents - administration &amp; dosage</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Male</subject><subject>nifedipine</subject><subject>Nifedipine - administration &amp; dosage</subject><subject>Nifedipine - adverse effects</subject><subject>Nifedipine - pharmacology</subject><subject>PTEN Phosphohydrolase - drug effects</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN protein</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>tacrolimus</subject><subject>Tacrolimus - administration &amp; dosage</subject><subject>Tacrolimus - adverse effects</subject><subject>Tacrolimus - pharmacology</subject><subject>Time Factors</subject><issn>0022-3492</issn><issn>1943-3670</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LAzEURYMoWqtrd5KlC6fN1ySTpZRalaIidR2STCKRmaROOor_3pFRt64eD869j3cAOMNohiUi89e0nRGE6QwTVLJyD0ywZLSgXKB9MEGIkIIySY7Acc6vw4oZRYfgiFBSyYpXE_C09N7ZXYbJw422XWpC22eoYw3vg3d12IboLuFVk6KDqYMhwkVqTYh6F1K8hCnCVYgv4V03cBNy7l0-AQdeN9md_swpeL5ebhY3xfphdbu4WheWMkoLL70XxjJDhZCS1sbKylaCIF9Tx6mxlXTIEyuY18i4mluPmK5rybkxXFd0Ci7G3m2X3oa7O9WGbF3T6OhSnxVmQpQci5IM6HxEhwdz7pxX2y60uvtUGKlvkWoQqb5FqlHkkDj_Ke9N6-o__tfcAJQj8BEa9_lfn7p7XD5hLij9AjLTf0E</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Pamuk, Ferda</creator><creator>Cetinkaya, Burcu Ozkan</creator><creator>Gulbahar, Mustafa Yavuz</creator><creator>Gacar, Ayhan</creator><creator>Cayır Keles, Gonca</creator><creator>Erisgin, Zuleyha</creator><creator>Arik, Nurol</creator><general>American Academy of Periodontology</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>7X8</scope></search><sort><creationdate>201311</creationdate><title>Effects of Tacrolimus and Nifedipine, Alone or in Combination, on Gingival Tissues</title><author>Pamuk, Ferda ; 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dosage</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Male</topic><topic>nifedipine</topic><topic>Nifedipine - administration &amp; dosage</topic><topic>Nifedipine - adverse effects</topic><topic>Nifedipine - pharmacology</topic><topic>PTEN Phosphohydrolase - drug effects</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN protein</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>tacrolimus</topic><topic>Tacrolimus - administration &amp; dosage</topic><topic>Tacrolimus - adverse effects</topic><topic>Tacrolimus - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pamuk, Ferda</creatorcontrib><creatorcontrib>Cetinkaya, Burcu Ozkan</creatorcontrib><creatorcontrib>Gulbahar, Mustafa Yavuz</creatorcontrib><creatorcontrib>Gacar, Ayhan</creatorcontrib><creatorcontrib>Cayır Keles, Gonca</creatorcontrib><creatorcontrib>Erisgin, Zuleyha</creatorcontrib><creatorcontrib>Arik, Nurol</creatorcontrib><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>Journal of periodontology (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pamuk, Ferda</au><au>Cetinkaya, Burcu Ozkan</au><au>Gulbahar, Mustafa Yavuz</au><au>Gacar, Ayhan</au><au>Cayır Keles, Gonca</au><au>Erisgin, Zuleyha</au><au>Arik, Nurol</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Tacrolimus and Nifedipine, Alone or in Combination, on Gingival Tissues</atitle><jtitle>Journal of periodontology (1970)</jtitle><addtitle>J Periodontol</addtitle><date>2013-11</date><risdate>2013</risdate><volume>84</volume><issue>11</issue><spage>1673</spage><epage>1682</epage><pages>1673-1682</pages><issn>0022-3492</issn><eissn>1943-3670</eissn><abstract>Background: The aim of this study is to compare gingival changes induced by short‐ and long‐term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug‐induced gingival overgrowth. Methods: Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8‐week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24‐week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry. Results: Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P &lt;0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P &lt;0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P &lt;0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P &lt;0.05). Conclusions: Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug‐induced gingival overgrowth.</abstract><cop>United States</cop><pub>American Academy of Periodontology</pub><pmid>23289868</pmid><doi>10.1902/jop.2013.120545</doi><tpages>10</tpages></addata></record>
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subjects Animals
Blood Vessels - drug effects
Calcium Channel Blockers - administration & dosage
Calcium Channel Blockers - adverse effects
Calcium Channel Blockers - pharmacology
Cell Count
Collagen - drug effects
Connective Tissue - drug effects
Connective Tissue - pathology
Dentistry
Drug Combinations
Epithelium - drug effects
Epithelium - pathology
Fibroblasts - drug effects
Fibroblasts - pathology
Gene Expression Regulation, Enzymologic - drug effects
Gingiva - drug effects
Gingiva - pathology
Gingival overgrowth
Gingival Overgrowth - chemically induced
immunohistochemistry
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - adverse effects
Immunosuppressive Agents - pharmacology
Male
nifedipine
Nifedipine - administration & dosage
Nifedipine - adverse effects
Nifedipine - pharmacology
PTEN Phosphohydrolase - drug effects
PTEN Phosphohydrolase - genetics
PTEN protein
Random Allocation
Rats
Rats, Sprague-Dawley
tacrolimus
Tacrolimus - administration & dosage
Tacrolimus - adverse effects
Tacrolimus - pharmacology
Time Factors
title Effects of Tacrolimus and Nifedipine, Alone or in Combination, on Gingival Tissues
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