5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition
[Display omitted] This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations...
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| Veröffentlicht in: | Biochemical pharmacology 2017-12, Vol.145, p.34-45 |
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| creator | Bomfin, Luana E. Braga, Cíntia M. Oliveira, Thais A. Martins, Conceição S. Foschetti, Danielle A. Santos, Ana A.Q.A. Costa, Deiziane V.S. Leitão, Renata F.C. Brito, Gerly A.C. |
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This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition. |
| doi_str_mv | 10.1016/j.bcp.2017.08.024 |
| format | Article |
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This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2017.08.024</identifier><identifier>PMID: 28867645</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>5-Fluorouracil ; Animals ; Antineoplastic Agents - adverse effects ; Cell Death - drug effects ; Cell Proliferation ; Cricetinae ; Fluorouracil - adverse effects ; Inflammation ; Major salivary glands ; Mucositis - chemically induced ; Mucositis - pathology ; Oxidative stress ; Saliva - chemistry ; Saliva - physiology ; Salivary Glands - drug effects ; Salivary Glands - pathology ; Xerostomia</subject><ispartof>Biochemical pharmacology, 2017-12, Vol.145, p.34-45</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-edc18cd6dbffa795c6c5bb92af62a4a1429c4ff134068def2a39343a18c896853</citedby><cites>FETCH-LOGICAL-c353t-edc18cd6dbffa795c6c5bb92af62a4a1429c4ff134068def2a39343a18c896853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006295217305622$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28867645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bomfin, Luana E.</creatorcontrib><creatorcontrib>Braga, Cíntia M.</creatorcontrib><creatorcontrib>Oliveira, Thais A.</creatorcontrib><creatorcontrib>Martins, Conceição S.</creatorcontrib><creatorcontrib>Foschetti, Danielle A.</creatorcontrib><creatorcontrib>Santos, Ana A.Q.A.</creatorcontrib><creatorcontrib>Costa, Deiziane V.S.</creatorcontrib><creatorcontrib>Leitão, Renata F.C.</creatorcontrib><creatorcontrib>Brito, Gerly A.C.</creatorcontrib><title>5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>[Display omitted]
This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.</description><subject>5-Fluorouracil</subject><subject>Animals</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Cell Death - drug effects</subject><subject>Cell Proliferation</subject><subject>Cricetinae</subject><subject>Fluorouracil - adverse effects</subject><subject>Inflammation</subject><subject>Major salivary glands</subject><subject>Mucositis - chemically induced</subject><subject>Mucositis - pathology</subject><subject>Oxidative stress</subject><subject>Saliva - chemistry</subject><subject>Saliva - physiology</subject><subject>Salivary Glands - drug effects</subject><subject>Salivary Glands - pathology</subject><subject>Xerostomia</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFO3DAQhq0KVBboA3BBPnJJajuJ11FPFeq2SEhc4Gw59ph6lcSLnWzh3gfvpAvtjYM1Hvuff2Y-Qi44Kznj8vO27OyuFIyvS6ZKJuoPZMXVuipEK9URWTHGJN4bcUJOc94uqZL8IzkRSsm1rJsV-d0Um36OKc7J2NDTMLrZQsboezMMZgpxpGZ0ND4Hh9keaJ4S5EVBp59AB7ONiWbTh71JL_SxR3GmxnuwUxgf___4Pv7663R4oTYOu5jD0uCcHHvTZ_j0Gs_Iw-bb_fWP4vbu-83119vCVk01FeAsV9ZJ13lv1m1jpW26rhXGS2Fqw2vR2tp7XtW4pwMvTNVWdWWwSCGQpjojVwffXYpPM-RJDyFb6HFmiHPWvMU-eBhDKT9IbYo5J_B6l8KAe2jO9AJfbzXC1wt8zZRG-Fhz-Wo_dwO4fxVvtFHw5SAAXHIfIOlsA4wWXEiIS7sY3rH_AxlLmHY</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Bomfin, Luana E.</creator><creator>Braga, Cíntia M.</creator><creator>Oliveira, Thais A.</creator><creator>Martins, Conceição S.</creator><creator>Foschetti, Danielle A.</creator><creator>Santos, Ana A.Q.A.</creator><creator>Costa, Deiziane V.S.</creator><creator>Leitão, Renata F.C.</creator><creator>Brito, Gerly A.C.</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20171201</creationdate><title>5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition</title><author>Bomfin, Luana E. ; Braga, Cíntia M. ; Oliveira, Thais A. ; Martins, Conceição S. ; Foschetti, Danielle A. ; Santos, Ana A.Q.A. ; Costa, Deiziane V.S. ; Leitão, Renata F.C. ; Brito, Gerly A.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-edc18cd6dbffa795c6c5bb92af62a4a1429c4ff134068def2a39343a18c896853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>5-Fluorouracil</topic><topic>Animals</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Cell Death - drug effects</topic><topic>Cell Proliferation</topic><topic>Cricetinae</topic><topic>Fluorouracil - adverse effects</topic><topic>Inflammation</topic><topic>Major salivary glands</topic><topic>Mucositis - chemically induced</topic><topic>Mucositis - pathology</topic><topic>Oxidative stress</topic><topic>Saliva - chemistry</topic><topic>Saliva - physiology</topic><topic>Salivary Glands - drug effects</topic><topic>Salivary Glands - pathology</topic><topic>Xerostomia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bomfin, Luana E.</creatorcontrib><creatorcontrib>Braga, Cíntia M.</creatorcontrib><creatorcontrib>Oliveira, Thais A.</creatorcontrib><creatorcontrib>Martins, Conceição S.</creatorcontrib><creatorcontrib>Foschetti, Danielle A.</creatorcontrib><creatorcontrib>Santos, Ana A.Q.A.</creatorcontrib><creatorcontrib>Costa, Deiziane V.S.</creatorcontrib><creatorcontrib>Leitão, Renata F.C.</creatorcontrib><creatorcontrib>Brito, Gerly A.C.</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>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bomfin, Luana E.</au><au>Braga, Cíntia M.</au><au>Oliveira, Thais A.</au><au>Martins, Conceição S.</au><au>Foschetti, Danielle A.</au><au>Santos, Ana A.Q.A.</au><au>Costa, Deiziane V.S.</au><au>Leitão, Renata F.C.</au><au>Brito, Gerly A.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>145</volume><spage>34</spage><epage>45</epage><pages>34-45</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><abstract>[Display omitted]
This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>28867645</pmid><doi>10.1016/j.bcp.2017.08.024</doi><tpages>12</tpages></addata></record> |
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| subjects | 5-Fluorouracil Animals Antineoplastic Agents - adverse effects Cell Death - drug effects Cell Proliferation Cricetinae Fluorouracil - adverse effects Inflammation Major salivary glands Mucositis - chemically induced Mucositis - pathology Oxidative stress Saliva - chemistry Saliva - physiology Salivary Glands - drug effects Salivary Glands - pathology Xerostomia |
| title | 5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition |
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