title: Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats.
abstract: The aim of the present study was to evaluate the effects of Quercetin (Qctn), a plant based flavonol, on retinal oxidative stress, neuroinflammation and apoptosis in streptozotocin-induced diabetic rats. Qctn treatment (25- and 50 mg/kg body weight) was given orally for six months in diabetic rats. Retinal glutathione (GSH) and antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] were estimated using commercially available assays, and inflammatory cytokines levels [tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β)] were estimated by ELISA method. Immunofluorescence and western blot studies were performed for nuclear factor kappa B (NF-kB), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) expressions. Structural changes were evaluated by light microscopy. In the present study, retinal GSH levels and antioxidant enzyme (SOD and CAT) activities were significantly decreased in diabetic group as compared to normal group. However, in Qctn-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of antioxidant enzyme activities was observed. Diabetic retinas showed significantly increased expression of pro-inflammatory cytokines (TNF-α and IL-1β) as compared to that in normal retinas, while Qctn-treated retinas showed significantly lower levels of cytokines as compared to diabetic retinas. Light microscopy showed significantly increased number of ganglion cell death and decreased retinal thickness in diabetic group compared to those in normal retina; however, protective effect of Qctn was seen. Increased apoptosis in diabetic retina is proposed to be mediated by overexpression of NF-kB and caspase-3. However, Qctn showed inhibitory effects on NF-kB and caspase-3 expression. Microglia showed upregulated GFAP expression, and inflammation of Müller cells resulted in edema in their endfeet and around perivascular space in nerve fiber layer in diabetic retina, as observed through AQP4 expression. However, Qctn treatments inhibited diabetes-induced increases in GFAP and AQP4 expression. Based on these findings, it can be concluded that bioflavonoids, such as Qctn can be effective for protection of diabetes induced retinal neurodegeneration and oxidative stress.
authors: Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences & Research, University of Delhi, New Delhi 110017, India; School of Medicine, Wayne State University, MI, USA. Electronic address: binitkumar35@gmail.com.
authors: Binit
authors: B
authors: Kumar
authors: Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences & Research, University of Delhi, New Delhi 110017, India. Electronic address: skgup@hotmail.com.
authors: Suresh Kumar
authors: SK
authors: Gupta
authors: Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.
authors: Tapas Chandra
authors: TC
authors: Nag
authors: Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences & Research, University of Delhi, New Delhi 110017, India.
authors: Sushma
authors: S
authors: Srivastava
authors: Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India.
authors: Rohit
authors: R
authors: Saxena
authors: Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.
authors: Kumar Abhiram
authors: KA
authors: Jha
authors: Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences & Research, University of Delhi, New Delhi 110017, India.
authors: Bharthu Parthasarthy
authors: BP
authors: Srinivasan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051401:Aquaporin 4 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D011794:Quercetin; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione
keywords: GFAP; apoptosis; aquaporin-4; bioflavonoid; neuroinflammation; quercetin