Effective blockade of RAAS by combination of aliskiren and olmesartan improves glucose homeostasis, glomerular filtration rate along with renal variables in streptozotocin induced diabetic rats
The present study aims to investigate the combined and individual treatment of aliskiren and olmesartan for 8weeks in streptozotocin induced diabetic rats provide an effective blockade of RAAS by improving glucose homeostasis, glomerular filtration rate along with renal variables thereby delaying th...
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| Veröffentlicht in: | European journal of pharmaceutical sciences 2012-05, Vol.46 (1-2), p.32-42 |
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| creator | Gandhi, Sonia Srinivasan, B.P. Akarte, Atul Sureshrao |
| description | The present study aims to investigate the combined and individual treatment of aliskiren and olmesartan for 8weeks in streptozotocin induced diabetic rats provide an effective blockade of RAAS by improving glucose homeostasis, glomerular filtration rate along with renal variables thereby delaying the progression of the disease. Streptozotocin induced diabetic rats were administered with aliskiren (10mg/kg/day), olmesartan (6mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications. |
| doi_str_mv | 10.1016/j.ejps.2012.02.002 |
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Streptozotocin induced diabetic rats were administered with aliskiren (10mg/kg/day), olmesartan (6mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications.</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2012.02.002</identifier><identifier>PMID: 22349361</identifier><language>eng</language><publisher>Kindlington: Elsevier B.V</publisher><subject><![CDATA[Amides - administration & dosage ; Amides - therapeutic use ; Angiotensin II Type 1 Receptor Blockers - administration & dosage ; Angiotensin II Type 1 Receptor Blockers - therapeutic use ; Animals ; Antifibrotic ; Antihypertensive Agents - administration & dosage ; Antiproteinuric ; Biological and medical sciences ; Blood Glucose - metabolism ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - physiopathology ; Drug Therapy, Combination ; Fumarates - administration & dosage ; Fumarates - therapeutic use ; General pharmacology ; Glomerular filtration rate ; Glomerular Filtration Rate - drug effects ; Glucose homeostasis ; Glucose Transporter Type 2 - analysis ; Glucose Transporter Type 4 - analysis ; Humans ; Imidazoles - administration & dosage ; Imidazoles - therapeutic use ; Insulin - blood ; Kidney - drug effects ; Kidney - physiopathology ; Liver - chemistry ; Medical sciences ; Muscle, Skeletal - chemistry ; Pharmaceutical technology. 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Streptozotocin induced diabetic rats were administered with aliskiren (10mg/kg/day), olmesartan (6mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications.</description><subject>Amides - administration & dosage</subject><subject>Amides - therapeutic use</subject><subject>Angiotensin II Type 1 Receptor Blockers - administration & dosage</subject><subject>Angiotensin II Type 1 Receptor Blockers - therapeutic use</subject><subject>Animals</subject><subject>Antifibrotic</subject><subject>Antihypertensive Agents - administration & dosage</subject><subject>Antiproteinuric</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Drug Therapy, Combination</subject><subject>Fumarates - administration & dosage</subject><subject>Fumarates - therapeutic use</subject><subject>General pharmacology</subject><subject>Glomerular filtration rate</subject><subject>Glomerular Filtration Rate - drug effects</subject><subject>Glucose homeostasis</subject><subject>Glucose Transporter Type 2 - analysis</subject><subject>Glucose Transporter Type 4 - analysis</subject><subject>Humans</subject><subject>Imidazoles - administration & dosage</subject><subject>Imidazoles - therapeutic use</subject><subject>Insulin - blood</subject><subject>Kidney - drug effects</subject><subject>Kidney - physiopathology</subject><subject>Liver - chemistry</subject><subject>Medical sciences</subject><subject>Muscle, Skeletal - chemistry</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>RAAS</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Serum Albumin - analysis</subject><subject>Tetrazoles - administration & dosage</subject><subject>Tetrazoles - therapeutic use</subject><subject>Time Factors</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1rVDEUhoModlr9Ay4kG3HjjEnuN7gZSq1CQfBjHZLckzbT3GTMyR2p_85_Zi4z6k44EE7y5CE5LyEvONtwxtu3uw3s9rgRjIsNK8XEI7LifTesWSfYY7Jig-jXbOi7M3KOuGOMtX3HnpIzIap6qFq-Ir-urAWT3QGo9tHcqxFotPTzdvuF6gdq4qRdUNnFsGwr7_DeJQhUhZFGPwGqlFWgbtqneACkt342EYHexQkiZoUO35TN0qXZq0St8zkdfWWBYozhlv5w-Y4WrfL0oJJT2heVCxRzgn2OP2OOprQujLOBkY6FgOzMosBn5IlVHuH5ab0g395ffb38sL75dP3xcnuzNlXf5LWuqrYRhgmt63YUVghba9vUPdQWGFcDq0zX8HYwlve8B8G7WtRGN-V4qHpRXZDXR2_56fcZMMvJoQHvVYA4oxzaMlPR9LyQ4kiaFBETWLlPblLpQXIml-TkTi7JySU5yUqxRf_ypJ_1BOPfK3-iKsCrE6DQKG-TCsbhP67pBG_qqnDvjhyUYRwcJInGQShzK8GZLMfo_veO32K9u_8</recordid><startdate>20120512</startdate><enddate>20120512</enddate><creator>Gandhi, Sonia</creator><creator>Srinivasan, B.P.</creator><creator>Akarte, Atul Sureshrao</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>20120512</creationdate><title>Effective blockade of RAAS by combination of aliskiren and olmesartan improves glucose homeostasis, glomerular filtration rate along with renal variables in streptozotocin induced diabetic rats</title><author>Gandhi, Sonia ; Srinivasan, B.P. ; Akarte, Atul Sureshrao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-b33652c02bb46d2f22f4bf548e4fe01a903c75169cf1818e217424cb54fe93823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Amides - administration & dosage</topic><topic>Amides - therapeutic use</topic><topic>Angiotensin II Type 1 Receptor Blockers - administration & dosage</topic><topic>Angiotensin II Type 1 Receptor Blockers - therapeutic use</topic><topic>Animals</topic><topic>Antifibrotic</topic><topic>Antihypertensive Agents - administration & dosage</topic><topic>Antiproteinuric</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Drug Therapy, Combination</topic><topic>Fumarates - administration & dosage</topic><topic>Fumarates - therapeutic use</topic><topic>General pharmacology</topic><topic>Glomerular filtration rate</topic><topic>Glomerular Filtration Rate - drug effects</topic><topic>Glucose homeostasis</topic><topic>Glucose Transporter Type 2 - analysis</topic><topic>Glucose Transporter Type 4 - analysis</topic><topic>Humans</topic><topic>Imidazoles - administration & dosage</topic><topic>Imidazoles - therapeutic use</topic><topic>Insulin - blood</topic><topic>Kidney - drug effects</topic><topic>Kidney - physiopathology</topic><topic>Liver - chemistry</topic><topic>Medical sciences</topic><topic>Muscle, Skeletal - chemistry</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>RAAS</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Serum Albumin - analysis</topic><topic>Tetrazoles - administration & dosage</topic><topic>Tetrazoles - therapeutic use</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gandhi, Sonia</creatorcontrib><creatorcontrib>Srinivasan, B.P.</creatorcontrib><creatorcontrib>Akarte, Atul Sureshrao</creatorcontrib><collection>Pascal-Francis</collection><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>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gandhi, Sonia</au><au>Srinivasan, B.P.</au><au>Akarte, Atul Sureshrao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effective blockade of RAAS by combination of aliskiren and olmesartan improves glucose homeostasis, glomerular filtration rate along with renal variables in streptozotocin induced diabetic rats</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2012-05-12</date><risdate>2012</risdate><volume>46</volume><issue>1-2</issue><spage>32</spage><epage>42</epage><pages>32-42</pages><issn>0928-0987</issn><eissn>1879-0720</eissn><abstract>The present study aims to investigate the combined and individual treatment of aliskiren and olmesartan for 8weeks in streptozotocin induced diabetic rats provide an effective blockade of RAAS by improving glucose homeostasis, glomerular filtration rate along with renal variables thereby delaying the progression of the disease. Streptozotocin induced diabetic rats were administered with aliskiren (10mg/kg/day), olmesartan (6mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications.</abstract><cop>Kindlington</cop><pub>Elsevier B.V</pub><pmid>22349361</pmid><doi>10.1016/j.ejps.2012.02.002</doi><tpages>11</tpages></addata></record> |
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| subjects | Amides - administration & dosage Amides - therapeutic use Angiotensin II Type 1 Receptor Blockers - administration & dosage Angiotensin II Type 1 Receptor Blockers - therapeutic use Animals Antifibrotic Antihypertensive Agents - administration & dosage Antiproteinuric Biological and medical sciences Blood Glucose - metabolism Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - physiopathology Drug Therapy, Combination Fumarates - administration & dosage Fumarates - therapeutic use General pharmacology Glomerular filtration rate Glomerular Filtration Rate - drug effects Glucose homeostasis Glucose Transporter Type 2 - analysis Glucose Transporter Type 4 - analysis Humans Imidazoles - administration & dosage Imidazoles - therapeutic use Insulin - blood Kidney - drug effects Kidney - physiopathology Liver - chemistry Medical sciences Muscle, Skeletal - chemistry Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments RAAS Rats Rats, Wistar Renin-Angiotensin System - drug effects Serum Albumin - analysis Tetrazoles - administration & dosage Tetrazoles - therapeutic use Time Factors |
| title | Effective blockade of RAAS by combination of aliskiren and olmesartan improves glucose homeostasis, glomerular filtration rate along with renal variables in streptozotocin induced diabetic rats |
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