Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats
Objective: The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats. Methods: Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damag...
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| Veröffentlicht in: | Human & experimental toxicology 2020-11, Vol.39 (11), p.1545-1555 |
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| creator | Saeedan, AS Rastogi, S Ansari, MN |
| description | Objective:
The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats.
Methods:
Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology.
Results:
DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa.
Conclusion:
The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage. |
| doi_str_mv | 10.1177/0960327120931165 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_AFRWT</sourceid><recordid>TN_cdi_proquest_journals_2430620943</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0960327120931165</sage_id><sourcerecordid>2430620943</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-b6d16f3707e7217b1f7e9806210b73b5b7ecc7a161afd1aef8075c34cfe7fe993</originalsourceid><addsrcrecordid>eNp1kE1LxDAURYMozji6dyUB19X3mjaZLGX8GGFEkBGXJU0T6dA2NWkX_ntbOioIrt7innseXELOEa4QhbgGyYHFAmOQDJGnB2SOiRARSGCHZD7G0ZjPyEkIOwDgMsVjMmNxGidLjnOyfXG26uuyUqGj2vVNZ7zSXaC3T-uobIpem4K23jTGtSNT6oGqXEMLVat3Q8uGqiovG0ffytApT73qwik5sqoK5mx_F-T1_m67Wkeb54fH1c0m0oynXZTzArllAoQRMYocrTByCTxGyAXL01wYrYVCjsoWqIxdgkg1S7Q1whop2YJcTt7Wu4_ehC7bud43w8ssTtggApmwgYKJ0t6F4I3NWl_Wyn9mCNk4Y_Z3xqFysRf3eW2Kn8L3bgMQTUAYRvj9-q_wCwJEees</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2430620943</pqid></control><display><type>article</type><title>Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats</title><source>Sage Journals GOLD Open Access 2024</source><creator>Saeedan, AS ; Rastogi, S ; Ansari, MN</creator><creatorcontrib>Saeedan, AS ; Rastogi, S ; Ansari, MN</creatorcontrib><description>Objective:
The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats.
Methods:
Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology.
Results:
DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa.
Conclusion:
The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.</description><identifier>ISSN: 0960-3271</identifier><identifier>EISSN: 1477-0903</identifier><identifier>DOI: 10.1177/0960327120931165</identifier><identifier>PMID: 32524861</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>1,2-Dimethylhydrazine ; Albinism ; Aminopyridines - pharmacology ; Aminopyridines - therapeutic use ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Antioxidants ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Benzamides - pharmacology ; Benzamides - therapeutic use ; Catalase ; Catalase - metabolism ; Colon ; Colon - drug effects ; Colon - metabolism ; Colon - pathology ; Colonic Neoplasms ; Colorectal cancer ; Crypts ; Cyclopropanes - pharmacology ; Cyclopropanes - therapeutic use ; Damage ; Dimethylhydrazines ; Glutathione ; Glutathione reductase ; Glutathione Reductase - metabolism ; Goblet cells ; Heart rate ; Hemodynamics ; Histopathology ; Hydrogen sulfide ; Hydrogen Sulfide - metabolism ; Inflammation ; Lamina propria ; Lipoxygenase - metabolism ; Male ; Markers ; Mucosa ; Nitric acid ; Nitric oxide ; Nitric Oxide - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Phosphodiesterase 4 Inhibitors - pharmacology ; Phosphodiesterase 4 Inhibitors - therapeutic use ; Precancerous Conditions - chemically induced ; Precancerous Conditions - drug therapy ; Precancerous Conditions - metabolism ; Precancerous Conditions - pathology ; Prostaglandin-Endoperoxide Synthases - metabolism ; Rats, Wistar ; Reductases ; Rodents ; Superoxide dismutase ; Superoxide Dismutase - metabolism ; Thiobarbituric acid</subject><ispartof>Human & experimental toxicology, 2020-11, Vol.39 (11), p.1545-1555</ispartof><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-b6d16f3707e7217b1f7e9806210b73b5b7ecc7a161afd1aef8075c34cfe7fe993</citedby><cites>FETCH-LOGICAL-c365t-b6d16f3707e7217b1f7e9806210b73b5b7ecc7a161afd1aef8075c34cfe7fe993</cites><orcidid>0000-0001-8580-3002</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0960327120931165$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0960327120931165$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21965,27852,27923,27924,44944,45332</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0960327120931165?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32524861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saeedan, AS</creatorcontrib><creatorcontrib>Rastogi, S</creatorcontrib><creatorcontrib>Ansari, MN</creatorcontrib><title>Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats</title><title>Human & experimental toxicology</title><addtitle>Hum Exp Toxicol</addtitle><description>Objective:
The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats.
Methods:
Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology.
Results:
DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa.
Conclusion:
The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.</description><subject>1,2-Dimethylhydrazine</subject><subject>Albinism</subject><subject>Aminopyridines - pharmacology</subject><subject>Aminopyridines - therapeutic use</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Benzamides - pharmacology</subject><subject>Benzamides - therapeutic use</subject><subject>Catalase</subject><subject>Catalase - metabolism</subject><subject>Colon</subject><subject>Colon - drug effects</subject><subject>Colon - metabolism</subject><subject>Colon - pathology</subject><subject>Colonic Neoplasms</subject><subject>Colorectal cancer</subject><subject>Crypts</subject><subject>Cyclopropanes - pharmacology</subject><subject>Cyclopropanes - therapeutic use</subject><subject>Damage</subject><subject>Dimethylhydrazines</subject><subject>Glutathione</subject><subject>Glutathione reductase</subject><subject>Glutathione Reductase - metabolism</subject><subject>Goblet cells</subject><subject>Heart rate</subject><subject>Hemodynamics</subject><subject>Histopathology</subject><subject>Hydrogen sulfide</subject><subject>Hydrogen Sulfide - metabolism</subject><subject>Inflammation</subject><subject>Lamina propria</subject><subject>Lipoxygenase - metabolism</subject><subject>Male</subject><subject>Markers</subject><subject>Mucosa</subject><subject>Nitric acid</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Phosphodiesterase 4 Inhibitors - pharmacology</subject><subject>Phosphodiesterase 4 Inhibitors - therapeutic use</subject><subject>Precancerous Conditions - chemically induced</subject><subject>Precancerous Conditions - drug therapy</subject><subject>Precancerous Conditions - metabolism</subject><subject>Precancerous Conditions - pathology</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Rats, Wistar</subject><subject>Reductases</subject><subject>Rodents</subject><subject>Superoxide dismutase</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Thiobarbituric acid</subject><issn>0960-3271</issn><issn>1477-0903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LxDAURYMozji6dyUB19X3mjaZLGX8GGFEkBGXJU0T6dA2NWkX_ntbOioIrt7innseXELOEa4QhbgGyYHFAmOQDJGnB2SOiRARSGCHZD7G0ZjPyEkIOwDgMsVjMmNxGidLjnOyfXG26uuyUqGj2vVNZ7zSXaC3T-uobIpem4K23jTGtSNT6oGqXEMLVat3Q8uGqiovG0ffytApT73qwik5sqoK5mx_F-T1_m67Wkeb54fH1c0m0oynXZTzArllAoQRMYocrTByCTxGyAXL01wYrYVCjsoWqIxdgkg1S7Q1whop2YJcTt7Wu4_ehC7bud43w8ssTtggApmwgYKJ0t6F4I3NWl_Wyn9mCNk4Y_Z3xqFysRf3eW2Kn8L3bgMQTUAYRvj9-q_wCwJEees</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Saeedan, AS</creator><creator>Rastogi, S</creator><creator>Ansari, MN</creator><general>SAGE Publications</general><general>Sage Publications Ltd</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>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>SOI</scope><orcidid>https://orcid.org/0000-0001-8580-3002</orcidid></search><sort><creationdate>202011</creationdate><title>Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats</title><author>Saeedan, AS ; Rastogi, S ; Ansari, MN</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-b6d16f3707e7217b1f7e9806210b73b5b7ecc7a161afd1aef8075c34cfe7fe993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1,2-Dimethylhydrazine</topic><topic>Albinism</topic><topic>Aminopyridines - pharmacology</topic><topic>Aminopyridines - therapeutic use</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Benzamides - pharmacology</topic><topic>Benzamides - therapeutic use</topic><topic>Catalase</topic><topic>Catalase - metabolism</topic><topic>Colon</topic><topic>Colon - drug effects</topic><topic>Colon - metabolism</topic><topic>Colon - pathology</topic><topic>Colonic Neoplasms</topic><topic>Colorectal cancer</topic><topic>Crypts</topic><topic>Cyclopropanes - pharmacology</topic><topic>Cyclopropanes - therapeutic use</topic><topic>Damage</topic><topic>Dimethylhydrazines</topic><topic>Glutathione</topic><topic>Glutathione reductase</topic><topic>Glutathione Reductase - metabolism</topic><topic>Goblet cells</topic><topic>Heart rate</topic><topic>Hemodynamics</topic><topic>Histopathology</topic><topic>Hydrogen sulfide</topic><topic>Hydrogen Sulfide - metabolism</topic><topic>Inflammation</topic><topic>Lamina propria</topic><topic>Lipoxygenase - metabolism</topic><topic>Male</topic><topic>Markers</topic><topic>Mucosa</topic><topic>Nitric acid</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Phosphodiesterase 4 Inhibitors - pharmacology</topic><topic>Phosphodiesterase 4 Inhibitors - therapeutic use</topic><topic>Precancerous Conditions - chemically induced</topic><topic>Precancerous Conditions - drug therapy</topic><topic>Precancerous Conditions - metabolism</topic><topic>Precancerous Conditions - pathology</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Rats, Wistar</topic><topic>Reductases</topic><topic>Rodents</topic><topic>Superoxide dismutase</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Thiobarbituric acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saeedan, AS</creatorcontrib><creatorcontrib>Rastogi, S</creatorcontrib><creatorcontrib>Ansari, MN</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Environment Abstracts</collection><jtitle>Human & experimental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Saeedan, AS</au><au>Rastogi, S</au><au>Ansari, MN</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats</atitle><jtitle>Human & experimental toxicology</jtitle><addtitle>Hum Exp Toxicol</addtitle><date>2020-11</date><risdate>2020</risdate><volume>39</volume><issue>11</issue><spage>1545</spage><epage>1555</epage><pages>1545-1555</pages><issn>0960-3271</issn><eissn>1477-0903</eissn><abstract>Objective:
The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats.
Methods:
Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology.
Results:
DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa.
Conclusion:
The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>32524861</pmid><doi>10.1177/0960327120931165</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8580-3002</orcidid></addata></record> |
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| issn | 0960-3271 1477-0903 |
| language | eng |
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| source | Sage Journals GOLD Open Access 2024 |
| subjects | 1,2-Dimethylhydrazine Albinism Aminopyridines - pharmacology Aminopyridines - therapeutic use Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Antioxidants Antioxidants - pharmacology Antioxidants - therapeutic use Benzamides - pharmacology Benzamides - therapeutic use Catalase Catalase - metabolism Colon Colon - drug effects Colon - metabolism Colon - pathology Colonic Neoplasms Colorectal cancer Crypts Cyclopropanes - pharmacology Cyclopropanes - therapeutic use Damage Dimethylhydrazines Glutathione Glutathione reductase Glutathione Reductase - metabolism Goblet cells Heart rate Hemodynamics Histopathology Hydrogen sulfide Hydrogen Sulfide - metabolism Inflammation Lamina propria Lipoxygenase - metabolism Male Markers Mucosa Nitric acid Nitric oxide Nitric Oxide - metabolism Oxidative stress Oxidative Stress - drug effects Phosphodiesterase 4 Inhibitors - pharmacology Phosphodiesterase 4 Inhibitors - therapeutic use Precancerous Conditions - chemically induced Precancerous Conditions - drug therapy Precancerous Conditions - metabolism Precancerous Conditions - pathology Prostaglandin-Endoperoxide Synthases - metabolism Rats, Wistar Reductases Rodents Superoxide dismutase Superoxide Dismutase - metabolism Thiobarbituric acid |
| title | Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats |
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