PI3K/Akt and Nrf2/HO-1 pathways involved in the hepatoprotective effect of verapamil against thioacetamide toxicity in rats
Liver is a precious organ to maintain body life. Hepatotoxicity is a worldwide health problem that is still a challenge for research. Although countless pharmaceutical drugs and herbal compounds were screened for their hepatoprotective effects, the death from hepatotoxicity is increasing. Thus, ther...
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| Veröffentlicht in: | Human & experimental toxicology 2019-04, Vol.38 (4), p.381-388 |
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| creator | Mohamed, MZ Hafez, HM Hassan, M Ibrahim, MA |
| description | Liver is a precious organ to maintain body life. Hepatotoxicity is a worldwide health problem that is still a challenge for research. Although countless pharmaceutical drugs and herbal compounds were screened for their hepatoprotective effects, the death from hepatotoxicity is increasing. Thus, there is continuous necessity of searching for the hepatoprotective effect of commonly used drugs. Accordingly, our aim was to examine a hepatoprotective potential for the antihypertensive drug, verapamil, and searching for new insights underlie its protective mechanism. Four groups of adult male rats were randomly arranged as controls, thioacetamide (TAA) hepatotoxic, and TAA + verapamil treated. Serum liver enzyme, hepatic antioxidant, lipid peroxidation, and inflammatory parameters were assessed. Gene relative expression for heme oxygenase-1 (HO-1), nuclear factor-erythroid 2-related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), and serine/threonine-specific protein kinase (Akt) were quantified in hepatic tissue. TAA caused hepatic injury evident both histopathologically and biochemically by a decrease in all gene expressions. Verapamil alleviated the injury via its antioxidant and anti-inflammatory effects that were suggested to be via upregulation of the previous gene expressions. In conclusion, the calcium channel blocker, verapamil, that is used widely as antihypertensive exhibits a valuable hepatoprotective effect. The protection partially rests on activation of Nrf2/HO-1 and PI3K/Akt pathways. |
| doi_str_mv | 10.1177/0960327118817099 |
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Hepatotoxicity is a worldwide health problem that is still a challenge for research. Although countless pharmaceutical drugs and herbal compounds were screened for their hepatoprotective effects, the death from hepatotoxicity is increasing. Thus, there is continuous necessity of searching for the hepatoprotective effect of commonly used drugs. Accordingly, our aim was to examine a hepatoprotective potential for the antihypertensive drug, verapamil, and searching for new insights underlie its protective mechanism. Four groups of adult male rats were randomly arranged as controls, thioacetamide (TAA) hepatotoxic, and TAA + verapamil treated. Serum liver enzyme, hepatic antioxidant, lipid peroxidation, and inflammatory parameters were assessed. Gene relative expression for heme oxygenase-1 (HO-1), nuclear factor-erythroid 2-related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), and serine/threonine-specific protein kinase (Akt) were quantified in hepatic tissue. TAA caused hepatic injury evident both histopathologically and biochemically by a decrease in all gene expressions. Verapamil alleviated the injury via its antioxidant and anti-inflammatory effects that were suggested to be via upregulation of the previous gene expressions. In conclusion, the calcium channel blocker, verapamil, that is used widely as antihypertensive exhibits a valuable hepatoprotective effect. The protection partially rests on activation of Nrf2/HO-1 and PI3K/Akt pathways.</description><identifier>ISSN: 0960-3271</identifier><identifier>EISSN: 1477-0903</identifier><identifier>DOI: 10.1177/0960327118817099</identifier><identifier>PMID: 30526075</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Antihypertensives ; Antioxidants ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Calcium ; Calcium channel blockers ; Calcium Channel Blockers - pharmacology ; Calcium Channel Blockers - therapeutic use ; Chemical and Drug Induced Liver Injury - drug therapy ; Chemical and Drug Induced Liver Injury - genetics ; Chemical and Drug Induced Liver Injury - pathology ; Drugs ; Gene expression ; Heme ; Heme oxygenase (decyclizing) ; Heme Oxygenase (Decyclizing) - genetics ; Hepatotoxicity ; Inflammation ; Kinases ; Lipid peroxidation ; Lipids ; Liver ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Male ; NF-E2-Related Factor 2 - genetics ; Oxygenase ; Peroxidation ; Phosphatidylinositol 3-Kinases - genetics ; Protein kinase ; Proteins ; Proto-Oncogene Proteins c-akt - genetics ; Rats ; Rodents ; Searching ; Signal Transduction ; Thioacetamide ; Threonine ; Toxicity ; Verapamil ; Verapamil - pharmacology ; Verapamil - therapeutic use</subject><ispartof>Human & experimental toxicology, 2019-04, Vol.38 (4), p.381-388</ispartof><rights>The Author(s) 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-1b0459300f57d30b15813d723b07027461788a52d549d5f5d71ffaf3d2acc023</citedby><cites>FETCH-LOGICAL-c365t-1b0459300f57d30b15813d723b07027461788a52d549d5f5d71ffaf3d2acc023</cites><orcidid>0000-0003-4246-210X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0960327118817099$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0960327118817099$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21966,27853,27924,27925,44945,45333</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0960327118817099?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/30526075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohamed, MZ</creatorcontrib><creatorcontrib>Hafez, HM</creatorcontrib><creatorcontrib>Hassan, M</creatorcontrib><creatorcontrib>Ibrahim, MA</creatorcontrib><title>PI3K/Akt and Nrf2/HO-1 pathways involved in the hepatoprotective effect of verapamil against thioacetamide toxicity in rats</title><title>Human & experimental toxicology</title><addtitle>Hum Exp Toxicol</addtitle><description>Liver is a precious organ to maintain body life. Hepatotoxicity is a worldwide health problem that is still a challenge for research. Although countless pharmaceutical drugs and herbal compounds were screened for their hepatoprotective effects, the death from hepatotoxicity is increasing. Thus, there is continuous necessity of searching for the hepatoprotective effect of commonly used drugs. Accordingly, our aim was to examine a hepatoprotective potential for the antihypertensive drug, verapamil, and searching for new insights underlie its protective mechanism. Four groups of adult male rats were randomly arranged as controls, thioacetamide (TAA) hepatotoxic, and TAA + verapamil treated. Serum liver enzyme, hepatic antioxidant, lipid peroxidation, and inflammatory parameters were assessed. Gene relative expression for heme oxygenase-1 (HO-1), nuclear factor-erythroid 2-related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), and serine/threonine-specific protein kinase (Akt) were quantified in hepatic tissue. TAA caused hepatic injury evident both histopathologically and biochemically by a decrease in all gene expressions. Verapamil alleviated the injury via its antioxidant and anti-inflammatory effects that were suggested to be via upregulation of the previous gene expressions. In conclusion, the calcium channel blocker, verapamil, that is used widely as antihypertensive exhibits a valuable hepatoprotective effect. The protection partially rests on activation of Nrf2/HO-1 and PI3K/Akt pathways.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Antihypertensives</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Calcium</subject><subject>Calcium channel blockers</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channel Blockers - therapeutic use</subject><subject>Chemical and Drug Induced Liver Injury - drug therapy</subject><subject>Chemical and Drug Induced Liver Injury - genetics</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Drugs</subject><subject>Gene expression</subject><subject>Heme</subject><subject>Heme oxygenase (decyclizing)</subject><subject>Heme Oxygenase (Decyclizing) - genetics</subject><subject>Hepatotoxicity</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Lipid peroxidation</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>Oxygenase</subject><subject>Peroxidation</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Rats</subject><subject>Rodents</subject><subject>Searching</subject><subject>Signal Transduction</subject><subject>Thioacetamide</subject><subject>Threonine</subject><subject>Toxicity</subject><subject>Verapamil</subject><subject>Verapamil - pharmacology</subject><subject>Verapamil - therapeutic use</subject><issn>0960-3271</issn><issn>1477-0903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UEtPAjEQboxGEL17Mk08r8y02-32SIyvaNSD903ZtrAILLYFJf55S0BNTDzNZL7X5CPkFOECUco-qAI4k4hliRKU2iNdzKXMQAHfJ90NnG3wDjkKYQIAhRJ4SDocBCtAii75fL7j9_3Ba6R6buijd6x_-5QhXeg4ftfrQJv5qp2urEkLjWNLxzZB7cK30daxWVlqnUsbbR1dWa8XetZMqR7pZh5iEjStrm1MR2NpbD-auonrjZXXMRyTA6enwZ7sZo-8XF-9XN5mD083d5eDh6zmhYgZDiEXigM4IQ2HIYoSuZGMD0ECk3mBsiy1YEbkyggnjETntOOG6boGxnvkfGubnn5b2hCrSbv085RYMUx9qBxBJRZsWbVvQ_DWVQvfzLRfVwjVpuzqb9lJcrYzXg5n1vwIvttNhGxLCHpkf1P_NfwCHDaF4w</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Mohamed, MZ</creator><creator>Hafez, HM</creator><creator>Hassan, M</creator><creator>Ibrahim, MA</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/0000-0003-4246-210X</orcidid></search><sort><creationdate>201904</creationdate><title>PI3K/Akt and Nrf2/HO-1 pathways involved in the hepatoprotective effect of verapamil against thioacetamide toxicity in rats</title><author>Mohamed, MZ ; Hafez, HM ; Hassan, M ; Ibrahim, MA</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-1b0459300f57d30b15813d723b07027461788a52d549d5f5d71ffaf3d2acc023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Antihypertensives</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Calcium</topic><topic>Calcium channel blockers</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channel Blockers - therapeutic use</topic><topic>Chemical and Drug Induced Liver Injury - drug therapy</topic><topic>Chemical and Drug Induced Liver Injury - genetics</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Drugs</topic><topic>Gene expression</topic><topic>Heme</topic><topic>Heme oxygenase (decyclizing)</topic><topic>Heme Oxygenase (Decyclizing) - genetics</topic><topic>Hepatotoxicity</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Lipid peroxidation</topic><topic>Lipids</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>Oxygenase</topic><topic>Peroxidation</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Rats</topic><topic>Rodents</topic><topic>Searching</topic><topic>Signal Transduction</topic><topic>Thioacetamide</topic><topic>Threonine</topic><topic>Toxicity</topic><topic>Verapamil</topic><topic>Verapamil - pharmacology</topic><topic>Verapamil - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohamed, MZ</creatorcontrib><creatorcontrib>Hafez, HM</creatorcontrib><creatorcontrib>Hassan, M</creatorcontrib><creatorcontrib>Ibrahim, MA</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>Mohamed, MZ</au><au>Hafez, HM</au><au>Hassan, M</au><au>Ibrahim, MA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PI3K/Akt and Nrf2/HO-1 pathways involved in the hepatoprotective effect of verapamil against thioacetamide toxicity in rats</atitle><jtitle>Human & experimental toxicology</jtitle><addtitle>Hum Exp Toxicol</addtitle><date>2019-04</date><risdate>2019</risdate><volume>38</volume><issue>4</issue><spage>381</spage><epage>388</epage><pages>381-388</pages><issn>0960-3271</issn><eissn>1477-0903</eissn><abstract>Liver is a precious organ to maintain body life. Hepatotoxicity is a worldwide health problem that is still a challenge for research. Although countless pharmaceutical drugs and herbal compounds were screened for their hepatoprotective effects, the death from hepatotoxicity is increasing. Thus, there is continuous necessity of searching for the hepatoprotective effect of commonly used drugs. Accordingly, our aim was to examine a hepatoprotective potential for the antihypertensive drug, verapamil, and searching for new insights underlie its protective mechanism. Four groups of adult male rats were randomly arranged as controls, thioacetamide (TAA) hepatotoxic, and TAA + verapamil treated. Serum liver enzyme, hepatic antioxidant, lipid peroxidation, and inflammatory parameters were assessed. Gene relative expression for heme oxygenase-1 (HO-1), nuclear factor-erythroid 2-related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), and serine/threonine-specific protein kinase (Akt) were quantified in hepatic tissue. TAA caused hepatic injury evident both histopathologically and biochemically by a decrease in all gene expressions. Verapamil alleviated the injury via its antioxidant and anti-inflammatory effects that were suggested to be via upregulation of the previous gene expressions. In conclusion, the calcium channel blocker, verapamil, that is used widely as antihypertensive exhibits a valuable hepatoprotective effect. The protection partially rests on activation of Nrf2/HO-1 and PI3K/Akt pathways.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>30526075</pmid><doi>10.1177/0960327118817099</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4246-210X</orcidid></addata></record> |
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| ispartof | Human & experimental toxicology, 2019-04, Vol.38 (4), p.381-388 |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Antihypertensives Antioxidants Antioxidants - pharmacology Antioxidants - therapeutic use Calcium Calcium channel blockers Calcium Channel Blockers - pharmacology Calcium Channel Blockers - therapeutic use Chemical and Drug Induced Liver Injury - drug therapy Chemical and Drug Induced Liver Injury - genetics Chemical and Drug Induced Liver Injury - pathology Drugs Gene expression Heme Heme oxygenase (decyclizing) Heme Oxygenase (Decyclizing) - genetics Hepatotoxicity Inflammation Kinases Lipid peroxidation Lipids Liver Liver - drug effects Liver - metabolism Liver - pathology Male NF-E2-Related Factor 2 - genetics Oxygenase Peroxidation Phosphatidylinositol 3-Kinases - genetics Protein kinase Proteins Proto-Oncogene Proteins c-akt - genetics Rats Rodents Searching Signal Transduction Thioacetamide Threonine Toxicity Verapamil Verapamil - pharmacology Verapamil - therapeutic use |
| title | PI3K/Akt and Nrf2/HO-1 pathways involved in the hepatoprotective effect of verapamil against thioacetamide toxicity in rats |
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