Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats
The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Super...
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| Veröffentlicht in: | Microvascular research 2013-05, Vol.87, p.65-74 |
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| creator | Kumar, Binit Gupta, Suresh Kumar Srinivasan, B.P. Nag, Tapas Chandra Srivastava, Sushma Saxena, Rohit Jha, Kumar Abhiram |
| description | The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Superoxide dismutase; SOD, Catalase; CAT and glutathione; GSH) enzymes, inflammatory cytokines (TNF-α, IL-1β), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4(AQP4) expression. Histological changes were evaluated by light and transmission electron microscopic (LM and TEM) studies. Retinal GSH levels and anti-oxidant enzymes (SOD and CAT) activity were significantly decreased in diabetic group as compared to normal group. However, in Hsp-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of anti-oxidant enzyme activity was observed. Diabetic retinae showed significantly increased expression of Pro-inflammatory cytokines (TNF-α and IL-1β) as compared to normal retinae. While Hsp-treated retinae showed significantly lower levels of cytokines as compared to diabetic retinae. Diabetic retinae showed increased caspase-3, GFAP and AQP4 expression. However, Hsp-treated retinae showed inhibitory effect on caspase-3, GFAP and AQP4 expression. LM images showed edematous Müller cell endfeet, and also degenerated photoreceptor layer; however, protective effect of Hsp was seen on Müller cell processes and photoreceptors. TEM study showed increased basement membrane (BM) thickness in diabetic retina, while relatively thin BM was recorded in Hsp-treated retina. It can be postulated that dietary flavanoids, like Hsp, can be effective for the prevention of diabetes induced neurovascular complications such as diabetic retinopathy.
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► Hesperetin inhibits expression of pro-inflammatory cytokines (TNF-α and IL-1β) in diabetic retina. ► Hesperetin protects hyperglycaemia-induced photoreceptor and neural degeneration. ► Hesperetin prevents hyperglycaemia-induced retinal apoptosis. ► Hesperetin prevented thickening of BM in diabetic retina. |
| doi_str_mv | 10.1016/j.mvr.2013.01.002 |
| format | Article |
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[Display omitted]
► Hesperetin inhibits expression of pro-inflammatory cytokines (TNF-α and IL-1β) in diabetic retina. ► Hesperetin protects hyperglycaemia-induced photoreceptor and neural degeneration. ► Hesperetin prevents hyperglycaemia-induced retinal apoptosis. ► Hesperetin prevented thickening of BM in diabetic retina.</description><identifier>ISSN: 0026-2862</identifier><identifier>EISSN: 1095-9319</identifier><identifier>DOI: 10.1016/j.mvr.2013.01.002</identifier><identifier>PMID: 23376836</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Antioxidants - pharmacology ; Apoptosis - drug effects ; Aquaporin 4 - metabolism ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Body Weight - drug effects ; Caspase 3 - metabolism ; Catalase - metabolism ; Diabetes Mellitus, Experimental - chemically induced ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - immunology ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Experimental - pathology ; Diabetic Retinopathy - drug therapy ; Diabetic Retinopathy - immunology ; Diabetic Retinopathy - metabolism ; Diabetic Retinopathy - pathology ; Female ; Glial Fibrillary Acidic Protein - metabolism ; Glutathione - metabolism ; Hesperidin - pharmacology ; Immunohistochemistry ; Inflammation - drug therapy ; Inflammation - immunology ; Inflammation - metabolism ; Inflammation - pathology ; Inflammation Mediators - metabolism ; Interleukin-1beta - metabolism ; Male ; Microscopy, Electron, Transmission ; Oxidative Stress - drug effects ; Rats ; Rats, Wistar ; Retina - drug effects ; Retina - immunology ; Retina - metabolism ; Retina - ultrastructure ; Streptozocin ; Superoxide Dismutase - metabolism ; Time Factors ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Microvascular research, 2013-05, Vol.87, p.65-74</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-307c9ceedc0176eecbfb011d253c187006ac47e3c60a21a3f978c9b76c01f5093</citedby><cites>FETCH-LOGICAL-c353t-307c9ceedc0176eecbfb011d253c187006ac47e3c60a21a3f978c9b76c01f5093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mvr.2013.01.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23376836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, Binit</creatorcontrib><creatorcontrib>Gupta, Suresh Kumar</creatorcontrib><creatorcontrib>Srinivasan, B.P.</creatorcontrib><creatorcontrib>Nag, Tapas Chandra</creatorcontrib><creatorcontrib>Srivastava, Sushma</creatorcontrib><creatorcontrib>Saxena, Rohit</creatorcontrib><creatorcontrib>Jha, Kumar Abhiram</creatorcontrib><title>Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats</title><title>Microvascular research</title><addtitle>Microvasc Res</addtitle><description>The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Superoxide dismutase; SOD, Catalase; CAT and glutathione; GSH) enzymes, inflammatory cytokines (TNF-α, IL-1β), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4(AQP4) expression. Histological changes were evaluated by light and transmission electron microscopic (LM and TEM) studies. Retinal GSH levels and anti-oxidant enzymes (SOD and CAT) activity were significantly decreased in diabetic group as compared to normal group. However, in Hsp-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of anti-oxidant enzyme activity was observed. Diabetic retinae showed significantly increased expression of Pro-inflammatory cytokines (TNF-α and IL-1β) as compared to normal retinae. While Hsp-treated retinae showed significantly lower levels of cytokines as compared to diabetic retinae. Diabetic retinae showed increased caspase-3, GFAP and AQP4 expression. However, Hsp-treated retinae showed inhibitory effect on caspase-3, GFAP and AQP4 expression. LM images showed edematous Müller cell endfeet, and also degenerated photoreceptor layer; however, protective effect of Hsp was seen on Müller cell processes and photoreceptors. TEM study showed increased basement membrane (BM) thickness in diabetic retina, while relatively thin BM was recorded in Hsp-treated retina. It can be postulated that dietary flavanoids, like Hsp, can be effective for the prevention of diabetes induced neurovascular complications such as diabetic retinopathy.
[Display omitted]
► Hesperetin inhibits expression of pro-inflammatory cytokines (TNF-α and IL-1β) in diabetic retina. ► Hesperetin protects hyperglycaemia-induced photoreceptor and neural degeneration. ► Hesperetin prevents hyperglycaemia-induced retinal apoptosis. ► Hesperetin prevented thickening of BM in diabetic retina.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Aquaporin 4 - metabolism</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Body Weight - drug effects</subject><subject>Caspase 3 - metabolism</subject><subject>Catalase - metabolism</subject><subject>Diabetes Mellitus, Experimental - chemically induced</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - immunology</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetic Retinopathy - drug therapy</subject><subject>Diabetic Retinopathy - immunology</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>Diabetic Retinopathy - pathology</subject><subject>Female</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Glutathione - metabolism</subject><subject>Hesperidin - pharmacology</subject><subject>Immunohistochemistry</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Inflammation Mediators - metabolism</subject><subject>Interleukin-1beta - metabolism</subject><subject>Male</subject><subject>Microscopy, Electron, Transmission</subject><subject>Oxidative Stress - drug effects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Retina - drug effects</subject><subject>Retina - immunology</subject><subject>Retina - metabolism</subject><subject>Retina - ultrastructure</subject><subject>Streptozocin</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0026-2862</issn><issn>1095-9319</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpyG62-QG5BB17iN0ZKZbW5FRCPgoLvSTHImR5DFpsy5G8S_Lvo3Q3PfYkpHneF83D2AVCiYDqx7Yc9rEUgLIELAHEF7ZEqKuillh_Zcv8ogqxVmLBzlLaAiBWtThlCyGlVmupluzPI6WJIs1-5JGS21Hif2-25-HVt3b2e-JpzrN0xUfaxeDHrrfDkCdh5HZsuZ3CNIfkE88lrbdNzjse7Zy-sZPO9onOj-eKPd_fPd0-FpvfD79uf24KJys5FxK0qx1R6wC1InJN1-S_tqKSDtcaQFl3rUk6BVaglV2t165utMp8V0EtV-z7oXeK4SWvMJvBJ0d9b0cKu2RQCq2FRqkyigfUxZBSpM5M0Q82vhkE82HVbE22aj6sGkCTHebM5bF-1wzU_kt8aszAzQGgvOTeUzTJeRodtT6Sm00b_H_q3wFxs4me</recordid><startdate>201305</startdate><enddate>201305</enddate><creator>Kumar, Binit</creator><creator>Gupta, Suresh Kumar</creator><creator>Srinivasan, B.P.</creator><creator>Nag, Tapas Chandra</creator><creator>Srivastava, Sushma</creator><creator>Saxena, Rohit</creator><creator>Jha, Kumar Abhiram</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>201305</creationdate><title>Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats</title><author>Kumar, Binit ; Gupta, Suresh Kumar ; Srinivasan, B.P. ; Nag, Tapas Chandra ; Srivastava, Sushma ; Saxena, Rohit ; Jha, Kumar Abhiram</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-307c9ceedc0176eecbfb011d253c187006ac47e3c60a21a3f978c9b76c01f5093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Aquaporin 4 - metabolism</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Body Weight - drug effects</topic><topic>Caspase 3 - metabolism</topic><topic>Catalase - metabolism</topic><topic>Diabetes Mellitus, Experimental - chemically induced</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - immunology</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetic Retinopathy - drug therapy</topic><topic>Diabetic Retinopathy - immunology</topic><topic>Diabetic Retinopathy - metabolism</topic><topic>Diabetic Retinopathy - pathology</topic><topic>Female</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Glutathione - metabolism</topic><topic>Hesperidin - pharmacology</topic><topic>Immunohistochemistry</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Inflammation Mediators - metabolism</topic><topic>Interleukin-1beta - metabolism</topic><topic>Male</topic><topic>Microscopy, Electron, Transmission</topic><topic>Oxidative Stress - drug effects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Retina - drug effects</topic><topic>Retina - immunology</topic><topic>Retina - metabolism</topic><topic>Retina - ultrastructure</topic><topic>Streptozocin</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Time Factors</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumar, Binit</creatorcontrib><creatorcontrib>Gupta, Suresh Kumar</creatorcontrib><creatorcontrib>Srinivasan, B.P.</creatorcontrib><creatorcontrib>Nag, Tapas Chandra</creatorcontrib><creatorcontrib>Srivastava, Sushma</creatorcontrib><creatorcontrib>Saxena, Rohit</creatorcontrib><creatorcontrib>Jha, Kumar Abhiram</creatorcontrib><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>Microvascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, Binit</au><au>Gupta, Suresh Kumar</au><au>Srinivasan, B.P.</au><au>Nag, Tapas Chandra</au><au>Srivastava, Sushma</au><au>Saxena, Rohit</au><au>Jha, Kumar Abhiram</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats</atitle><jtitle>Microvascular research</jtitle><addtitle>Microvasc Res</addtitle><date>2013-05</date><risdate>2013</risdate><volume>87</volume><spage>65</spage><epage>74</epage><pages>65-74</pages><issn>0026-2862</issn><eissn>1095-9319</eissn><abstract>The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Superoxide dismutase; SOD, Catalase; CAT and glutathione; GSH) enzymes, inflammatory cytokines (TNF-α, IL-1β), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4(AQP4) expression. Histological changes were evaluated by light and transmission electron microscopic (LM and TEM) studies. Retinal GSH levels and anti-oxidant enzymes (SOD and CAT) activity were significantly decreased in diabetic group as compared to normal group. However, in Hsp-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of anti-oxidant enzyme activity was observed. Diabetic retinae showed significantly increased expression of Pro-inflammatory cytokines (TNF-α and IL-1β) as compared to normal retinae. While Hsp-treated retinae showed significantly lower levels of cytokines as compared to diabetic retinae. Diabetic retinae showed increased caspase-3, GFAP and AQP4 expression. However, Hsp-treated retinae showed inhibitory effect on caspase-3, GFAP and AQP4 expression. LM images showed edematous Müller cell endfeet, and also degenerated photoreceptor layer; however, protective effect of Hsp was seen on Müller cell processes and photoreceptors. TEM study showed increased basement membrane (BM) thickness in diabetic retina, while relatively thin BM was recorded in Hsp-treated retina. It can be postulated that dietary flavanoids, like Hsp, can be effective for the prevention of diabetes induced neurovascular complications such as diabetic retinopathy.
[Display omitted]
► Hesperetin inhibits expression of pro-inflammatory cytokines (TNF-α and IL-1β) in diabetic retina. ► Hesperetin protects hyperglycaemia-induced photoreceptor and neural degeneration. ► Hesperetin prevents hyperglycaemia-induced retinal apoptosis. ► Hesperetin prevented thickening of BM in diabetic retina.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23376836</pmid><doi>10.1016/j.mvr.2013.01.002</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - pharmacology Antioxidants - pharmacology Apoptosis - drug effects Aquaporin 4 - metabolism Blood Glucose - drug effects Blood Glucose - metabolism Body Weight - drug effects Caspase 3 - metabolism Catalase - metabolism Diabetes Mellitus, Experimental - chemically induced Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - immunology Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Diabetic Retinopathy - drug therapy Diabetic Retinopathy - immunology Diabetic Retinopathy - metabolism Diabetic Retinopathy - pathology Female Glial Fibrillary Acidic Protein - metabolism Glutathione - metabolism Hesperidin - pharmacology Immunohistochemistry Inflammation - drug therapy Inflammation - immunology Inflammation - metabolism Inflammation - pathology Inflammation Mediators - metabolism Interleukin-1beta - metabolism Male Microscopy, Electron, Transmission Oxidative Stress - drug effects Rats Rats, Wistar Retina - drug effects Retina - immunology Retina - metabolism Retina - ultrastructure Streptozocin Superoxide Dismutase - metabolism Time Factors Tumor Necrosis Factor-alpha - metabolism |
| title | Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats |
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