Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune‐enzymatic, and gene expression analysis
Objective This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT). Background Estrogen deficiency is the main cause of osteoporosis and is related to higher periodontal attachment loss and reduction of alveolar bone...
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creator | Molez, Andréia Manetta Nascimento, Eduarda Helena Leandro Haiter Neto, Francisco Cirano, Fabiano Ribeiro Pimentel, Suzana Peres Ribeiro, Fernanda Vieira Casati, Marcio Zaffalon Corrêa, Mônica Grazieli |
description | Objective
This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT).
Background
Estrogen deficiency is the main cause of osteoporosis and is related to higher periodontal attachment loss and reduction of alveolar bone. Zoledronate (ZLD) is an antiresorptive drug used to control osteoporosis but can lead to osteonecrosis of the jaw. RESV, a natural product, can reduce bone loss and control and prevent osteoporosis. Thus, this study aimed at investigating the effect of RESV on the progression of EP in estrogen‐deficient rats.
Material and Methods
The animals were subjected to the OVT or sham surgery to induce estrogen‐deficiency and then were divided into the groups: OVT + RESV (n: 10); OVT + PLAC (n: 10): OVT + placebo; OVT + ZLD +PLA (n: 10); OVT + RESV +ZLD (n: 10): OVT + RESV and ZLD; SHAM (n: 10): non‐ovariectomized animals + placebo. To induce estrogen deficiency, the rats were subjected to ovariectomy. Experimental periodontitis was induced by the placement of a ligature at the second maxillary molars. Daily administration of the placebo solution, resveratrol (10 mg/kg), and ZLD (0.1 mg/kg) was carried out for a period 42 days prior to initiation of EP, and then for another 28 days following ligature placement. After euthanasia, the specimens were processed for micro‐CT and morphometric analysis of bone loss (linear measurement), and the gingival tissue surrounding the maxillary second molar was collected for the quantification of inflammatory markers using Luminex/MAGPix, of oxidative stress markers using ELISA assay, and gene expression analysis of bone markers, by real‐time PCR.
Results
Morphometric and micro‐CT analysis showed higher bone loss and lower bone density, respectively, in OVT + PLAC when compared to the other groups (P |
doi_str_mv | 10.1111/jre.12775 |
format | Article |
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This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT).
Background
Estrogen deficiency is the main cause of osteoporosis and is related to higher periodontal attachment loss and reduction of alveolar bone. Zoledronate (ZLD) is an antiresorptive drug used to control osteoporosis but can lead to osteonecrosis of the jaw. RESV, a natural product, can reduce bone loss and control and prevent osteoporosis. Thus, this study aimed at investigating the effect of RESV on the progression of EP in estrogen‐deficient rats.
Material and Methods
The animals were subjected to the OVT or sham surgery to induce estrogen‐deficiency and then were divided into the groups: OVT + RESV (n: 10); OVT + PLAC (n: 10): OVT + placebo; OVT + ZLD +PLA (n: 10); OVT + RESV +ZLD (n: 10): OVT + RESV and ZLD; SHAM (n: 10): non‐ovariectomized animals + placebo. To induce estrogen deficiency, the rats were subjected to ovariectomy. Experimental periodontitis was induced by the placement of a ligature at the second maxillary molars. Daily administration of the placebo solution, resveratrol (10 mg/kg), and ZLD (0.1 mg/kg) was carried out for a period 42 days prior to initiation of EP, and then for another 28 days following ligature placement. After euthanasia, the specimens were processed for micro‐CT and morphometric analysis of bone loss (linear measurement), and the gingival tissue surrounding the maxillary second molar was collected for the quantification of inflammatory markers using Luminex/MAGPix, of oxidative stress markers using ELISA assay, and gene expression analysis of bone markers, by real‐time PCR.
Results
Morphometric and micro‐CT analysis showed higher bone loss and lower bone density, respectively, in OVT + PLAC when compared to the other groups (P < .05). ZLD treated groups had lower alveolar bone loss, as well as, higher density and percentage of bone volume, when compared to OVT + RESV and SHAM + PLAC groups (P < .05). IL‐4 levels were significantly lower in the OVT + PLAC group versus OVT + ZLD +RESV and SHAM + PLAC (P < .05). NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) levels were significantly lower OVT + RESV group when compared to OVT + PLAC (P < .05). OPG mRNA levels were lower in OVT + PLAC compared with the SHAM + PLAC group (P < .05).
Conclusion
It can be concluded that resveratrol modulated alveolar bone loss during experimental periodontitis progression in estrogen‐deficient rats by downregulating NADPH oxidase levels.</description><identifier>ISSN: 0022-3484</identifier><identifier>EISSN: 1600-0765</identifier><identifier>DOI: 10.1111/jre.12775</identifier><identifier>PMID: 32976639</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Alveolar bone ; alveolar bone loss ; Alveolar Bone Loss - prevention & control ; Animals ; anti‐inflammatory ; Bone density ; Bone loss ; Dentistry ; Disease Models, Animal ; Down-Regulation ; Enzyme-linked immunosorbent assay ; estrogen deficiency ; Estrogens ; Female ; Gene Expression ; Gum disease ; Humans ; Inflammation ; Jaw ; Maxilla ; Molars ; Morphometry ; NAD(P)H oxidase ; NADPH Oxidases - metabolism ; NADPH-diaphorase ; Natural products ; Oophorectomy ; Osteonecrosis ; Osteoporosis ; Osteoporosis - drug therapy ; Osteoporosis - genetics ; Osteoporosis - prevention & control ; Osteoprotegerin ; Ovariectomy ; Oxidative stress ; Periodontitis ; Periodontitis - drug therapy ; Periodontitis - prevention & control ; Rats ; Rats, Wistar ; Resveratrol ; Resveratrol - pharmacology ; Surgery ; Teeth ; Zoledronic acid</subject><ispartof>Journal of periodontal research, 2020-12, Vol.55 (6), p.840-849</ispartof><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2020 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4195-b8eb13edb130295c12dd8f41f295c6745e01c2c1c41e8f35156ebd706fc7a57b3</citedby><cites>FETCH-LOGICAL-c4195-b8eb13edb130295c12dd8f41f295c6745e01c2c1c41e8f35156ebd706fc7a57b3</cites><orcidid>0000-0003-1895-3283 ; 0000-0002-2697-620X ; 0000-0002-3577-8600 ; 0000-0002-7331-4612 ; 0000-0001-9234-0536</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjre.12775$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjre.12775$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32976639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Molez, Andréia Manetta</creatorcontrib><creatorcontrib>Nascimento, Eduarda Helena Leandro</creatorcontrib><creatorcontrib>Haiter Neto, Francisco</creatorcontrib><creatorcontrib>Cirano, Fabiano Ribeiro</creatorcontrib><creatorcontrib>Pimentel, Suzana Peres</creatorcontrib><creatorcontrib>Ribeiro, Fernanda Vieira</creatorcontrib><creatorcontrib>Casati, Marcio Zaffalon</creatorcontrib><creatorcontrib>Corrêa, Mônica Grazieli</creatorcontrib><title>Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune‐enzymatic, and gene expression analysis</title><title>Journal of periodontal research</title><addtitle>J Periodontal Res</addtitle><description>Objective
This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT).
Background
Estrogen deficiency is the main cause of osteoporosis and is related to higher periodontal attachment loss and reduction of alveolar bone. Zoledronate (ZLD) is an antiresorptive drug used to control osteoporosis but can lead to osteonecrosis of the jaw. RESV, a natural product, can reduce bone loss and control and prevent osteoporosis. Thus, this study aimed at investigating the effect of RESV on the progression of EP in estrogen‐deficient rats.
Material and Methods
The animals were subjected to the OVT or sham surgery to induce estrogen‐deficiency and then were divided into the groups: OVT + RESV (n: 10); OVT + PLAC (n: 10): OVT + placebo; OVT + ZLD +PLA (n: 10); OVT + RESV +ZLD (n: 10): OVT + RESV and ZLD; SHAM (n: 10): non‐ovariectomized animals + placebo. To induce estrogen deficiency, the rats were subjected to ovariectomy. Experimental periodontitis was induced by the placement of a ligature at the second maxillary molars. Daily administration of the placebo solution, resveratrol (10 mg/kg), and ZLD (0.1 mg/kg) was carried out for a period 42 days prior to initiation of EP, and then for another 28 days following ligature placement. After euthanasia, the specimens were processed for micro‐CT and morphometric analysis of bone loss (linear measurement), and the gingival tissue surrounding the maxillary second molar was collected for the quantification of inflammatory markers using Luminex/MAGPix, of oxidative stress markers using ELISA assay, and gene expression analysis of bone markers, by real‐time PCR.
Results
Morphometric and micro‐CT analysis showed higher bone loss and lower bone density, respectively, in OVT + PLAC when compared to the other groups (P < .05). ZLD treated groups had lower alveolar bone loss, as well as, higher density and percentage of bone volume, when compared to OVT + RESV and SHAM + PLAC groups (P < .05). IL‐4 levels were significantly lower in the OVT + PLAC group versus OVT + ZLD +RESV and SHAM + PLAC (P < .05). NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) levels were significantly lower OVT + RESV group when compared to OVT + PLAC (P < .05). OPG mRNA levels were lower in OVT + PLAC compared with the SHAM + PLAC group (P < .05).
Conclusion
It can be concluded that resveratrol modulated alveolar bone loss during experimental periodontitis progression in estrogen‐deficient rats by downregulating NADPH oxidase levels.</description><subject>Alveolar bone</subject><subject>alveolar bone loss</subject><subject>Alveolar Bone Loss - prevention & control</subject><subject>Animals</subject><subject>anti‐inflammatory</subject><subject>Bone density</subject><subject>Bone loss</subject><subject>Dentistry</subject><subject>Disease Models, Animal</subject><subject>Down-Regulation</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>estrogen deficiency</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gum disease</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Jaw</subject><subject>Maxilla</subject><subject>Molars</subject><subject>Morphometry</subject><subject>NAD(P)H oxidase</subject><subject>NADPH Oxidases - metabolism</subject><subject>NADPH-diaphorase</subject><subject>Natural products</subject><subject>Oophorectomy</subject><subject>Osteonecrosis</subject><subject>Osteoporosis</subject><subject>Osteoporosis - drug therapy</subject><subject>Osteoporosis - genetics</subject><subject>Osteoporosis - prevention & control</subject><subject>Osteoprotegerin</subject><subject>Ovariectomy</subject><subject>Oxidative stress</subject><subject>Periodontitis</subject><subject>Periodontitis - drug therapy</subject><subject>Periodontitis - prevention & control</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Resveratrol</subject><subject>Resveratrol - pharmacology</subject><subject>Surgery</subject><subject>Teeth</subject><subject>Zoledronic acid</subject><issn>0022-3484</issn><issn>1600-0765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFu1TAQhi0Eoq-FBRdAlthQqWntJLaT7lD1KFStkBCsIyeetH5K7GA7hdcVR-AyXIiTMOG1LJDwwp4ZffN7ND8hLzg75nhONgGOea6UeERWXDKWMSXFY7JiLM-zoqzKPbIf44ZhLlX9lOwVea2kLOoV-bnue-gS9T0NEG8h6BT8QL2j6QboFPw1lqPFHAn4NkGwI7ikB7qE3niXbLKRWkc1Mrc6WJTzo70DQ1GMjt7AsDT7mMBPPvho4ym98mG68SOkYLsjasdxdvDr-w9wd9tRp6WmnaHX4GD59WEG7fSwxf5n5EmvhwjP798D8vnt-tPZu-zyw_n7szeXWVfyWmRtBS0vwODF8lp0PDem6kveL4lUpQDGu7zjSEPVF4ILCa1RTPad0kK1xQF5vdPFRXyZIaZmtLGDYdAO_BybvCylVFxVDNFX_6AbPwecd6FEXStViYU63FEd7iEG6JsJF6rDtuGsWbxs0Mvmj5fIvrxXnNsRzF_ywTwETnbAVzvA9v9KzcXH9U7yN0Qrrmk</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Molez, Andréia Manetta</creator><creator>Nascimento, Eduarda Helena Leandro</creator><creator>Haiter Neto, Francisco</creator><creator>Cirano, Fabiano Ribeiro</creator><creator>Pimentel, Suzana Peres</creator><creator>Ribeiro, Fernanda Vieira</creator><creator>Casati, Marcio Zaffalon</creator><creator>Corrêa, Mônica Grazieli</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1895-3283</orcidid><orcidid>https://orcid.org/0000-0002-2697-620X</orcidid><orcidid>https://orcid.org/0000-0002-3577-8600</orcidid><orcidid>https://orcid.org/0000-0002-7331-4612</orcidid><orcidid>https://orcid.org/0000-0001-9234-0536</orcidid></search><sort><creationdate>202012</creationdate><title>Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune‐enzymatic, and gene expression analysis</title><author>Molez, Andréia Manetta ; Nascimento, Eduarda Helena Leandro ; Haiter Neto, Francisco ; Cirano, Fabiano Ribeiro ; Pimentel, Suzana Peres ; Ribeiro, Fernanda Vieira ; Casati, Marcio Zaffalon ; Corrêa, Mônica Grazieli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4195-b8eb13edb130295c12dd8f41f295c6745e01c2c1c41e8f35156ebd706fc7a57b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alveolar bone</topic><topic>alveolar bone loss</topic><topic>Alveolar Bone Loss - prevention & control</topic><topic>Animals</topic><topic>anti‐inflammatory</topic><topic>Bone density</topic><topic>Bone loss</topic><topic>Dentistry</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>estrogen deficiency</topic><topic>Estrogens</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gum disease</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Jaw</topic><topic>Maxilla</topic><topic>Molars</topic><topic>Morphometry</topic><topic>NAD(P)H oxidase</topic><topic>NADPH Oxidases - metabolism</topic><topic>NADPH-diaphorase</topic><topic>Natural products</topic><topic>Oophorectomy</topic><topic>Osteonecrosis</topic><topic>Osteoporosis</topic><topic>Osteoporosis - drug therapy</topic><topic>Osteoporosis - genetics</topic><topic>Osteoporosis - prevention & control</topic><topic>Osteoprotegerin</topic><topic>Ovariectomy</topic><topic>Oxidative stress</topic><topic>Periodontitis</topic><topic>Periodontitis - drug therapy</topic><topic>Periodontitis - prevention & control</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Resveratrol</topic><topic>Resveratrol - pharmacology</topic><topic>Surgery</topic><topic>Teeth</topic><topic>Zoledronic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Molez, Andréia Manetta</creatorcontrib><creatorcontrib>Nascimento, Eduarda Helena Leandro</creatorcontrib><creatorcontrib>Haiter Neto, Francisco</creatorcontrib><creatorcontrib>Cirano, Fabiano Ribeiro</creatorcontrib><creatorcontrib>Pimentel, Suzana Peres</creatorcontrib><creatorcontrib>Ribeiro, Fernanda Vieira</creatorcontrib><creatorcontrib>Casati, Marcio Zaffalon</creatorcontrib><creatorcontrib>Corrêa, Mônica Grazieli</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of periodontal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Molez, Andréia Manetta</au><au>Nascimento, Eduarda Helena Leandro</au><au>Haiter Neto, Francisco</au><au>Cirano, Fabiano Ribeiro</au><au>Pimentel, Suzana Peres</au><au>Ribeiro, Fernanda Vieira</au><au>Casati, Marcio Zaffalon</au><au>Corrêa, Mônica Grazieli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune‐enzymatic, and gene expression analysis</atitle><jtitle>Journal of periodontal research</jtitle><addtitle>J Periodontal Res</addtitle><date>2020-12</date><risdate>2020</risdate><volume>55</volume><issue>6</issue><spage>840</spage><epage>849</epage><pages>840-849</pages><issn>0022-3484</issn><eissn>1600-0765</eissn><abstract>Objective
This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT).
Background
Estrogen deficiency is the main cause of osteoporosis and is related to higher periodontal attachment loss and reduction of alveolar bone. Zoledronate (ZLD) is an antiresorptive drug used to control osteoporosis but can lead to osteonecrosis of the jaw. RESV, a natural product, can reduce bone loss and control and prevent osteoporosis. Thus, this study aimed at investigating the effect of RESV on the progression of EP in estrogen‐deficient rats.
Material and Methods
The animals were subjected to the OVT or sham surgery to induce estrogen‐deficiency and then were divided into the groups: OVT + RESV (n: 10); OVT + PLAC (n: 10): OVT + placebo; OVT + ZLD +PLA (n: 10); OVT + RESV +ZLD (n: 10): OVT + RESV and ZLD; SHAM (n: 10): non‐ovariectomized animals + placebo. To induce estrogen deficiency, the rats were subjected to ovariectomy. Experimental periodontitis was induced by the placement of a ligature at the second maxillary molars. Daily administration of the placebo solution, resveratrol (10 mg/kg), and ZLD (0.1 mg/kg) was carried out for a period 42 days prior to initiation of EP, and then for another 28 days following ligature placement. After euthanasia, the specimens were processed for micro‐CT and morphometric analysis of bone loss (linear measurement), and the gingival tissue surrounding the maxillary second molar was collected for the quantification of inflammatory markers using Luminex/MAGPix, of oxidative stress markers using ELISA assay, and gene expression analysis of bone markers, by real‐time PCR.
Results
Morphometric and micro‐CT analysis showed higher bone loss and lower bone density, respectively, in OVT + PLAC when compared to the other groups (P < .05). ZLD treated groups had lower alveolar bone loss, as well as, higher density and percentage of bone volume, when compared to OVT + RESV and SHAM + PLAC groups (P < .05). IL‐4 levels were significantly lower in the OVT + PLAC group versus OVT + ZLD +RESV and SHAM + PLAC (P < .05). NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) levels were significantly lower OVT + RESV group when compared to OVT + PLAC (P < .05). OPG mRNA levels were lower in OVT + PLAC compared with the SHAM + PLAC group (P < .05).
Conclusion
It can be concluded that resveratrol modulated alveolar bone loss during experimental periodontitis progression in estrogen‐deficient rats by downregulating NADPH oxidase levels.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32976639</pmid><doi>10.1111/jre.12775</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-1895-3283</orcidid><orcidid>https://orcid.org/0000-0002-2697-620X</orcidid><orcidid>https://orcid.org/0000-0002-3577-8600</orcidid><orcidid>https://orcid.org/0000-0002-7331-4612</orcidid><orcidid>https://orcid.org/0000-0001-9234-0536</orcidid></addata></record> |
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subjects | Alveolar bone alveolar bone loss Alveolar Bone Loss - prevention & control Animals anti‐inflammatory Bone density Bone loss Dentistry Disease Models, Animal Down-Regulation Enzyme-linked immunosorbent assay estrogen deficiency Estrogens Female Gene Expression Gum disease Humans Inflammation Jaw Maxilla Molars Morphometry NAD(P)H oxidase NADPH Oxidases - metabolism NADPH-diaphorase Natural products Oophorectomy Osteonecrosis Osteoporosis Osteoporosis - drug therapy Osteoporosis - genetics Osteoporosis - prevention & control Osteoprotegerin Ovariectomy Oxidative stress Periodontitis Periodontitis - drug therapy Periodontitis - prevention & control Rats Rats, Wistar Resveratrol Resveratrol - pharmacology Surgery Teeth Zoledronic acid |
title | Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune‐enzymatic, and gene expression analysis |
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