title: Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats.
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 (100 mg/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.
authors: Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences & Research, University of Delhi, New Delhi, India. binitkumar35@gmail.com
authors: Binit
authors: B
authors: Kumar
authors: Suresh Kumar
authors: SK
authors: Gupta
authors: B P
authors: BP
authors: Srinivasan
authors: Tapas Chandra
authors: TC
authors: Nag
authors: Sushma
authors: S
authors: Srivastava
authors: Rohit
authors: R
authors: Saxena
authors: Kumar Abhiram
authors: KA
authors: Jha
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051401:Aquaporin 4 / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D001786:Blood Glucose; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D006569:Hesperidin; D002374:Catalase; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; C013015:hesperetin