Cadmium‐induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum

Background Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. Objectives This study aimed to explore how cadmium expos...

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Veröffentlicht in:Journal of biochemical and molecular toxicology 2019-04, Vol.33 (4), p.e22274-n/a
Hauptverfasser: P. M., Mubeena Mariyath, Shahi, Mehdi H., Tayyab, Mohd, Farheen, Shirin, Khanam, Nabeela, Tabassum, Sartaj, Ali, Asif
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container_end_page n/a
container_issue 4
container_start_page e22274
container_title Journal of biochemical and molecular toxicology
container_volume 33
creator P. M., Mubeena Mariyath
Shahi, Mehdi H.
Tayyab, Mohd
Farheen, Shirin
Khanam, Nabeela
Tabassum, Sartaj
Ali, Asif
description Background Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. Objectives This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Methods Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. Results A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium‐treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium‐treated rats.
doi_str_mv 10.1002/jbt.22274
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M., Mubeena Mariyath ; Shahi, Mehdi H. ; Tayyab, Mohd ; Farheen, Shirin ; Khanam, Nabeela ; Tabassum, Sartaj ; Ali, Asif</creator><creatorcontrib>P. M., Mubeena Mariyath ; Shahi, Mehdi H. ; Tayyab, Mohd ; Farheen, Shirin ; Khanam, Nabeela ; Tabassum, Sartaj ; Ali, Asif</creatorcontrib><description>Background Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. Objectives This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Methods Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. Results A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium‐treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium‐treated rats.</description><identifier>ISSN: 1095-6670</identifier><identifier>EISSN: 1099-0461</identifier><identifier>DOI: 10.1002/jbt.22274</identifier><identifier>PMID: 30506660</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Bioassays ; Body weight ; Brain ; Cadmium ; Cerebellum ; Comet assay ; Damage ; Damage detection ; Deoxyribonucleic acid ; DNA ; DNA damage ; Fuel consumption ; Heavy metals ; Hedgehog protein ; Motor activity ; Neurodegeneration ; Nkx2.2 ; Oxidative stress ; Pax6 ; Polymerase chain reaction ; Rodents ; Signal transduction ; Signaling ; sonic hedgehog ; Structural integrity ; Toxicity</subject><ispartof>Journal of biochemical and molecular toxicology, 2019-04, Vol.33 (4), p.e22274-n/a</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-f957a8a96fe2711aef866421df69fab44f5b7a639c06be0e4680e038ccd524d23</citedby><cites>FETCH-LOGICAL-c3534-f957a8a96fe2711aef866421df69fab44f5b7a639c06be0e4680e038ccd524d23</cites><orcidid>0000-0001-9589-4382</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbt.22274$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbt.22274$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30506660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>P. M., Mubeena Mariyath</creatorcontrib><creatorcontrib>Shahi, Mehdi H.</creatorcontrib><creatorcontrib>Tayyab, Mohd</creatorcontrib><creatorcontrib>Farheen, Shirin</creatorcontrib><creatorcontrib>Khanam, Nabeela</creatorcontrib><creatorcontrib>Tabassum, Sartaj</creatorcontrib><creatorcontrib>Ali, Asif</creatorcontrib><title>Cadmium‐induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum</title><title>Journal of biochemical and molecular toxicology</title><addtitle>J Biochem Mol Toxicol</addtitle><description>Background Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. Objectives This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Methods Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. Results A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium‐treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium‐treated rats.</description><subject>Bioassays</subject><subject>Body weight</subject><subject>Brain</subject><subject>Cadmium</subject><subject>Cerebellum</subject><subject>Comet assay</subject><subject>Damage</subject><subject>Damage detection</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Fuel consumption</subject><subject>Heavy metals</subject><subject>Hedgehog protein</subject><subject>Motor activity</subject><subject>Neurodegeneration</subject><subject>Nkx2.2</subject><subject>Oxidative stress</subject><subject>Pax6</subject><subject>Polymerase chain reaction</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>sonic hedgehog</subject><subject>Structural integrity</subject><subject>Toxicity</subject><issn>1095-6670</issn><issn>1099-0461</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kc1u1DAQxy0EoqVw4AWQJS5wSDt2bCc50hWfqsSlnCPHHu96SezFTqj2xiPwjDwJblM4IHGZD-k3_xnNn5DnDM4ZAL_YD_M557wRD8gpg66rQCj28K6WlVINnJAnOe8BQHaNfExOapCglIJT8nWj7eSX6dePnz7YxaClAZcULW4xYNKzj4HqYKk2s_--ttHREIPRJXijR5pvM92h3eIubulBz7sbfaQ-0DJPDSYccByX6Sl55PSY8dl9PiNf3r293nyorj6__7h5c1WZWtaicp1sdKs75ZA3jGl0rVKCM-tU5_QghJNDo1XdGVADAgrVAkLdGmMlF5bXZ-TVqntI8duCee4nn005QQeMS-45Ex1w0aqmoC__QfdxSaFc13MOrSyb67ZQr1fKpJhzQtcfkp90OvYM-lsH-uJAf-dAYV_cKy7DhPYv-eflBbhYgRs_4vH_Sv2ny-tV8jfn0pGy</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>P. M., Mubeena Mariyath</creator><creator>Shahi, Mehdi H.</creator><creator>Tayyab, Mohd</creator><creator>Farheen, Shirin</creator><creator>Khanam, Nabeela</creator><creator>Tabassum, Sartaj</creator><creator>Ali, Asif</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9589-4382</orcidid></search><sort><creationdate>201904</creationdate><title>Cadmium‐induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum</title><author>P. M., Mubeena Mariyath ; Shahi, Mehdi H. ; Tayyab, Mohd ; Farheen, Shirin ; Khanam, Nabeela ; Tabassum, Sartaj ; Ali, Asif</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-f957a8a96fe2711aef866421df69fab44f5b7a639c06be0e4680e038ccd524d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Bioassays</topic><topic>Body weight</topic><topic>Brain</topic><topic>Cadmium</topic><topic>Cerebellum</topic><topic>Comet assay</topic><topic>Damage</topic><topic>Damage detection</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Fuel consumption</topic><topic>Heavy metals</topic><topic>Hedgehog protein</topic><topic>Motor activity</topic><topic>Neurodegeneration</topic><topic>Nkx2.2</topic><topic>Oxidative stress</topic><topic>Pax6</topic><topic>Polymerase chain reaction</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>sonic hedgehog</topic><topic>Structural integrity</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>P. M., Mubeena Mariyath</creatorcontrib><creatorcontrib>Shahi, Mehdi H.</creatorcontrib><creatorcontrib>Tayyab, Mohd</creatorcontrib><creatorcontrib>Farheen, Shirin</creatorcontrib><creatorcontrib>Khanam, Nabeela</creatorcontrib><creatorcontrib>Tabassum, Sartaj</creatorcontrib><creatorcontrib>Ali, Asif</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biochemical and molecular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>P. M., Mubeena Mariyath</au><au>Shahi, Mehdi H.</au><au>Tayyab, Mohd</au><au>Farheen, Shirin</au><au>Khanam, Nabeela</au><au>Tabassum, Sartaj</au><au>Ali, Asif</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cadmium‐induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum</atitle><jtitle>Journal of biochemical and molecular toxicology</jtitle><addtitle>J Biochem Mol Toxicol</addtitle><date>2019-04</date><risdate>2019</risdate><volume>33</volume><issue>4</issue><spage>e22274</spage><epage>n/a</epage><pages>e22274-n/a</pages><issn>1095-6670</issn><eissn>1099-0461</eissn><abstract>Background Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. Objectives This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Methods Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. Results A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium‐treated samples. 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subjects Bioassays
Body weight
Brain
Cadmium
Cerebellum
Comet assay
Damage
Damage detection
Deoxyribonucleic acid
DNA
DNA damage
Fuel consumption
Heavy metals
Hedgehog protein
Motor activity
Neurodegeneration
Nkx2.2
Oxidative stress
Pax6
Polymerase chain reaction
Rodents
Signal transduction
Signaling
sonic hedgehog
Structural integrity
Toxicity
title Cadmium‐induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum
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