Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats
Clinical studies have shown that hyperglycemia can induce early‐stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial‐mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It...
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| Veröffentlicht in: | Environmental toxicology 2019-07, Vol.34 (7), p.861-868 |
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| creator | Peng, Xiang Su, Haiyan Liang, Dali Li, Jeihua Ting, Wei‐Jen Liao, Shih‐Chieh Huang, Chih‐Yang |
| description | Clinical studies have shown that hyperglycemia can induce early‐stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial‐mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)‐induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF‐β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co‐treatment of STZ‐induced DN rats showed that glomerulosclerosis in early‐stage DN was reversible (P |
| doi_str_mv | 10.1002/tox.22758 |
| format | Article |
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Furthermore, oxidative stress, tubular epithelial‐mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)‐induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF‐β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co‐treatment of STZ‐induced DN rats showed that glomerulosclerosis in early‐stage DN was reversible (P < .05 compared with that in STZ‐induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.22758</identifier><identifier>PMID: 31062909</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Accumulation ; Animals ; Collagen ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - chemically induced ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Diabetic Nephropathies - complications ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - pathology ; Diabetic Nephropathies - prevention & control ; Diabetic nephropathy ; Disease Progression ; Drug Therapy, Combination ; Extracellular ; Extracellular matrix ; Fibrosis ; glomerulosclerosis ; Glomerulosclerosis, Focal Segmental - pathology ; Glomerulosclerosis, Focal Segmental - prevention & control ; Glomerulus ; Hyperglycemia ; Kidney - drug effects ; Kidney - pathology ; Kidney diseases ; Male ; Mesenchyme ; Nephropathy ; Oxidative stress ; ramipril ; Ramipril - administration & dosage ; Rats ; Rats, Sprague-Dawley ; Resveratrol ; Resveratrol - administration & dosage ; Rho-associated kinase ; rho-Associated Kinases - metabolism ; rhoA GTP-Binding Protein - metabolism ; RhoA protein ; Rocks ; Rodents ; Severity of Illness Index ; Signal transduction ; Signal Transduction - drug effects ; Signs and symptoms ; Streptozocin ; Symptoms</subject><ispartof>Environmental toxicology, 2019-07, Vol.34 (7), p.861-868</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3908-f9b78fcf64ac4b8129a1a3ac2b69a1a290465a321b7107116a801411ff1fe9fd3</citedby><cites>FETCH-LOGICAL-c3908-f9b78fcf64ac4b8129a1a3ac2b69a1a290465a321b7107116a801411ff1fe9fd3</cites><orcidid>0000-0003-2347-0411</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%2Ftox.22758$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.22758$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31062909$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Xiang</creatorcontrib><creatorcontrib>Su, Haiyan</creatorcontrib><creatorcontrib>Liang, Dali</creatorcontrib><creatorcontrib>Li, Jeihua</creatorcontrib><creatorcontrib>Ting, Wei‐Jen</creatorcontrib><creatorcontrib>Liao, Shih‐Chieh</creatorcontrib><creatorcontrib>Huang, Chih‐Yang</creatorcontrib><title>Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Clinical studies have shown that hyperglycemia can induce early‐stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial‐mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)‐induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF‐β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co‐treatment of STZ‐induced DN rats showed that glomerulosclerosis in early‐stage DN was reversible (P < .05 compared with that in STZ‐induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.</description><subject>Accumulation</subject><subject>Animals</subject><subject>Collagen</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - chemically induced</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetic Nephropathies - complications</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>Diabetic nephropathy</subject><subject>Disease Progression</subject><subject>Drug Therapy, Combination</subject><subject>Extracellular</subject><subject>Extracellular matrix</subject><subject>Fibrosis</subject><subject>glomerulosclerosis</subject><subject>Glomerulosclerosis, Focal Segmental - pathology</subject><subject>Glomerulosclerosis, Focal Segmental - prevention & control</subject><subject>Glomerulus</subject><subject>Hyperglycemia</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Kidney diseases</subject><subject>Male</subject><subject>Mesenchyme</subject><subject>Nephropathy</subject><subject>Oxidative stress</subject><subject>ramipril</subject><subject>Ramipril - administration & dosage</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Resveratrol</subject><subject>Resveratrol - administration & dosage</subject><subject>Rho-associated kinase</subject><subject>rho-Associated Kinases - metabolism</subject><subject>rhoA GTP-Binding Protein - metabolism</subject><subject>RhoA protein</subject><subject>Rocks</subject><subject>Rodents</subject><subject>Severity of Illness Index</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signs and symptoms</subject><subject>Streptozocin</subject><subject>Symptoms</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQxi1ERUvhwAsgS1zgkK7t_HOO1QoKaqWVVkXiFk2cya4rJw62Q1lOfQReiJfhSXB22x4qcfLI8_u-Gfsj5A1nZ5wxsQj255kQZS6fkROeC5GUopTP9zVLMib5MXnp_Q1jrCry4gU5TjkrRMWqE_JnDb0enTYUhpY69D_QQXDWUGX_3v0ODiH0OAQKIeAwQUBP11t7vlivlpd0hLC9hV0EHW4mE7stRXBmvvEBNkhbDQ0GreiA49bZWTA3wXur9J7fGNujm4z1yqCzXnuqB-rj5DHYXzZEbogKPbSTivijYVzTvyJHHRiPr-_PU_L108fr5efkanXxZXl-lai0YjLpqqaUneqKDFTWSC4q4JCCEk0xV_EnsiKHVPCm5KzkvADJeMZ51_EOq65NT8n7g-_o7PcJfah77RUaAwPayddCRHHKMplF9N0T9MZObojbzVSWCsnymfpwoFR8sXfY1TGDHtyu5qyeM61jpvU-08i-vXecmh7bR_IhxAgsDsCtNrj7v1N9vfp2sPwH2pG1-g</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Peng, Xiang</creator><creator>Su, Haiyan</creator><creator>Liang, Dali</creator><creator>Li, Jeihua</creator><creator>Ting, Wei‐Jen</creator><creator>Liao, Shih‐Chieh</creator><creator>Huang, Chih‐Yang</creator><general>John Wiley & Sons, Inc</general><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>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2347-0411</orcidid></search><sort><creationdate>201907</creationdate><title>Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats</title><author>Peng, Xiang ; Su, Haiyan ; Liang, Dali ; Li, Jeihua ; Ting, Wei‐Jen ; Liao, Shih‐Chieh ; Huang, Chih‐Yang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3908-f9b78fcf64ac4b8129a1a3ac2b69a1a290465a321b7107116a801411ff1fe9fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Accumulation</topic><topic>Animals</topic><topic>Collagen</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - chemically induced</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetic Nephropathies - complications</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>Diabetic nephropathy</topic><topic>Disease Progression</topic><topic>Drug Therapy, Combination</topic><topic>Extracellular</topic><topic>Extracellular matrix</topic><topic>Fibrosis</topic><topic>glomerulosclerosis</topic><topic>Glomerulosclerosis, Focal Segmental - pathology</topic><topic>Glomerulosclerosis, Focal Segmental - prevention & control</topic><topic>Glomerulus</topic><topic>Hyperglycemia</topic><topic>Kidney - drug effects</topic><topic>Kidney - pathology</topic><topic>Kidney diseases</topic><topic>Male</topic><topic>Mesenchyme</topic><topic>Nephropathy</topic><topic>Oxidative stress</topic><topic>ramipril</topic><topic>Ramipril - administration & dosage</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Resveratrol</topic><topic>Resveratrol - administration & dosage</topic><topic>Rho-associated kinase</topic><topic>rho-Associated Kinases - metabolism</topic><topic>rhoA GTP-Binding Protein - metabolism</topic><topic>RhoA protein</topic><topic>Rocks</topic><topic>Rodents</topic><topic>Severity of Illness Index</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signs and symptoms</topic><topic>Streptozocin</topic><topic>Symptoms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Xiang</creatorcontrib><creatorcontrib>Su, Haiyan</creatorcontrib><creatorcontrib>Liang, Dali</creatorcontrib><creatorcontrib>Li, Jeihua</creatorcontrib><creatorcontrib>Ting, Wei‐Jen</creatorcontrib><creatorcontrib>Liao, Shih‐Chieh</creatorcontrib><creatorcontrib>Huang, Chih‐Yang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Xiang</au><au>Su, Haiyan</au><au>Liang, Dali</au><au>Li, Jeihua</au><au>Ting, Wei‐Jen</au><au>Liao, Shih‐Chieh</au><au>Huang, Chih‐Yang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2019-07</date><risdate>2019</risdate><volume>34</volume><issue>7</issue><spage>861</spage><epage>868</epage><pages>861-868</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Clinical studies have shown that hyperglycemia can induce early‐stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial‐mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)‐induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF‐β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co‐treatment of STZ‐induced DN rats showed that glomerulosclerosis in early‐stage DN was reversible (P < .05 compared with that in STZ‐induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>31062909</pmid><doi>10.1002/tox.22758</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-2347-0411</orcidid></addata></record> |
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| subjects | Accumulation Animals Collagen Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - chemically induced Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetic Nephropathies - complications Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology Diabetic Nephropathies - prevention & control Diabetic nephropathy Disease Progression Drug Therapy, Combination Extracellular Extracellular matrix Fibrosis glomerulosclerosis Glomerulosclerosis, Focal Segmental - pathology Glomerulosclerosis, Focal Segmental - prevention & control Glomerulus Hyperglycemia Kidney - drug effects Kidney - pathology Kidney diseases Male Mesenchyme Nephropathy Oxidative stress ramipril Ramipril - administration & dosage Rats Rats, Sprague-Dawley Resveratrol Resveratrol - administration & dosage Rho-associated kinase rho-Associated Kinases - metabolism rhoA GTP-Binding Protein - metabolism RhoA protein Rocks Rodents Severity of Illness Index Signal transduction Signal Transduction - drug effects Signs and symptoms Streptozocin Symptoms |
| title | Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats |
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