scholarly journals Superoxide dismutase 3 prevents early stage diabetic retinopathy in streptozotocin-induced diabetic rat model

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262396
Author(s):  
Ji-Yeon Lee ◽  
Mirinae Kim ◽  
Su Bin Oh ◽  
Hae-Young Kim ◽  
Chongtae Kim ◽  
...  

Purpose To identify the effects of superoxide dismutase (SOD)3 on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model. Methods Diabetic models were established by a single intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. After purification of the recombinant SOD3, intravitreal injection of SOD3 was performed at the time of STZ injection, and 1 and 2 weeks following STZ injection. Scotopic and photopic electroretinography (ERG) were recorded. Immunofluorescence staining with ɑ-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), pigment epithelium-derived factor (PEDF), Flt1, recoverin, parvalbumin, extracellular superoxide dismutase (SOD3), 8-Hydroxy-2’deoxyguanosine (8-OHdG) and tumor necrosis factor-ɑ (TNF-ɑ) were evaluated. Results In the scotopic ERG, the diabetic group showed reduced a- and b-wave amplitudes compared with the control group. In the photopic ERG, b-wave amplitude showed significant (p < 0.0005) reduction at 8 weeks following DM induction. However, the trend of a- and b-wave reduction was not evident in the SOD3 treated group. GFAP, Flt1, 8-OHdG and TNF-ɑ immunoreactivity were increased, and ɑ-SMA, PEDF and SOD3 immunoreactivity were decreased in the diabetic retina. The immunoreactivity of these markers was partially recovered in the SOD3 treated group. Parvalbumin expression was not decreased in the SOD3 treated group. In the diabetic retinas, the immunoreactivity of recoverin was weakly detected in both of the inner nuclear layer and inner plexiform layer compared to the control group but not in the SOD3 treated group. Conclusions SOD3 treatment attenuated the loss of a/b-wave amplitudes in the diabetic rats, which was consistent with the immunohistochemical evaluation. We also suggest that in rod-dominant rodents, the use of blue on green photopic negative response (PhNR) is effective in measuring the inner retinal function in animal models of diabetic retinopathy. SOD3 treatment ameliorated the retinal Müller cell activation in diabetic rats and pericyte dysfunction. These results suggested that SOD3 exerted protective effects on the development of diabetic retinopathy.

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Lingli Long ◽  
Yubin Li ◽  
Shuang Yu ◽  
Xiang Li ◽  
Yue Hu ◽  
...  

Background. Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. The antiangiogenic mechanisms of SCU in vitro and in vivo were investigated. Method. HRECs were cultured in high glucose- (30 mM D-glucose) and hypoxia (cobalt chloride-treated)-stimulated diabetic condition to evaluate the antiangiogenic effects of SCU by CCK-8 test, cell migration experiment (wound healing and transwell), and tube formation experiment. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. We further used western blot, luciferase reporter assay, and immunofluorescence staining to study the antiangiogenic mechanism of SCU. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats. Result. Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. SCU suppressed the crosstalk of phospho-ERK, phospho-FAK, phospho-Src, and VEGF in vivo and in vitro. Conclusions. These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src.


Author(s):  
Abbas Bakhteyari ◽  
Yasaman Zarrin ◽  
Parvaneh Nikpour ◽  
Zeinab Sadat Hosseiny ◽  
Zeinab Sadat Hosseiny ◽  
...  

Background: Diabetes mellitus deeply changes the genes expression of integrin (Itg) subunits in several cells and tissues such as monocytes, arterial endothelium, kidney glomerular cells, retina. Furthermore, hyperglycemia could impress and reduce the rate of successful assisted as well as non-assisted pregnancy. Endometrium undergoes thorough changes in normal menstrual cycle and the question is: What happens in the endometrium under diabetic condition? Objective: The aim of the current study was to investigate the endometrial gene expression of α3, α4, αv, Itg β1 and β3 subunits in diabetic rat models at the time of embryo implantation. Materials and Methods: Twenty-eight rats were randomly divided into 4 groups: control group, diabetic group, pioglitazone-treated group, and metformin-treated group. Real-time PCR was performed to determine changes in the expression of Itg α3, α4, αv, β1, and β3 genes in rat’s endometrium. Results: The expression of all Itg subunits increased significantly in diabetic rats’ endometrium compared with control group. Treatment with pioglitazone significantly reduced the level of Itg subunits gene expression compared with diabetic rats. While metformin had a different effect on α3 and α4 and elevated these two subunits gene expression. Conclusion: Diabetes mellitus significantly increased the expression of studied Itg subunits, therefore untreated diabetes could be potentially assumed as one of the preliminary elements in embryo implantation failure.


2020 ◽  
pp. 088532822096389
Author(s):  
Gamze Kara Magden ◽  
Cigdem Vural ◽  
Busra Yaprak Bayrak ◽  
Candan Yilmaz Ozdogan ◽  
Halime Kenar

Despite the fast development of technology in the world, diabetic foot wounds cause deaths and massive economical losses. Diabetes comes first among the reasons of non traumatic foot amputations. To reduce the healing time of these fast progressing wounds, effective wound dressings are in high demand. In our study, sheep small intestinal submucosa (SIS) based biocompatible sponges were prepared after SIS decellularization and their wound healing potential was investigated on full thickness skin defects in a diabetic rat model. The decellularized SIS membranes had no cytotoxic effects on human fibroblasts and supported capillary formation by HUVECs in a fibroblast-HUVEC co-culture. Glutaraldehyde crosslinked sponges of three different compositions were prepared to test in a diabetic rat model: gelatin (GS), gelatin: hyaluronic acid (GS:HA) and gelatin: hyaluronic acid: SIS (GS:HA:SIS). The GS:HA:SIS sponges underwent a 24.8 ± 5.4% weight loss in a 7-day in vitro erosion test. All sponges had a similar Young’s modulus under compression but GS:HA:SIS had the highest (5.00 ± 0.04 kPa). Statistical analyses of histopathological results of a 12-day in vivo experiment revealed no significant difference among the control, GS, GS:HA, and GS:HA:SIS transplanted groups in terms of granulation tissue thickness, collagen deposition, capillary vessel formation, and foreign body reaction (P > 0.05). On the other hand, in the GS:HA:SIS transplanted group 80% of the animals had a complete epidermal regeneration and this was significantly different than the control group (30%, P < 0.05). Preclinical studies revealed that the ECM of sheep small intestinal submucosa can be used as an effective biomaterial in diabetic wound healing.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Nima Tirgan ◽  
Gabriela A. Kulp ◽  
Praveena Gupta ◽  
Adam Boretsky ◽  
Tomasz A. Wiraszka ◽  
...  

Diabetes and smoking are known risk factors for cataract development. In this study, we evaluated the effect of nicotine on the progression of cataracts in a type 1 diabetic rat model. Diabetes was induced in Sprague-Dawley rats by a single injection of 65 mg/kg streptozotocin. Daily nicotine injections were administered subcutaneously. Forty-five rats were divided into groups of diabetics with and without nicotine treatment and controls with and without nicotine treatment. Progression of lens opacity was monitored using a slit lamp biomicroscope and scores were assigned. To assess whether systemic inflammation played a role in mediating cataractogenesis, we studied serum levels of eotaxin, IL-6, and IL-4. The levels of the measured cytokines increased significantly in nicotine-treated and untreated diabetic animals versus controls and demonstrated a positive trend in the nicotine-treated diabetic rats. Our data suggest the presence of a synergistic relationship between nicotine and diabetes that accelerated cataract formation via inflammatory mediators.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mengshan He ◽  
Pan Long ◽  
Lunfeng Guo ◽  
Mingke Zhang ◽  
Siwang Wang ◽  
...  

Aims. Diabetic retinopathy (DR) remains one of the leading causes of acquired blindness. Fushiming capsule (FSM), a compound traditional Chinese medicine, is clinically used for DR treatment in China. The present study was to investigate the effect of FSM on retinal alterations, inflammatory response, and oxidative stress triggered by diabetes. Main Methods. Diabetic rat model was induced by 6-week high-fat and high-sugar diet combined with 35 mg/kg streptozotocin (STZ). 30 days after successful establishment of diabetic rat model, full field electroretinography (ffERG) and optical coherence tomography (OCT) were performed to detect retinal pathological alterations. Then, FSM was administered to diabetic rats at different dosages for 42-day treatment and diabetic rats treated with Calcium dobesilate (CaD) capsule served as the positive group. Retinal function and structure were observed, and retinal vascular endothelial growth factor-α (VEGF-α), glial fibrillary acidic (GFAP), and vascular cell adhesion protein-1 (VCAM-1) expressions were measured both on mRNA and protein levels, and a series of blood metabolic indicators were also assessed. Key Findings. In DR rats, FSM (1.0 g/kg and 0.5 g/kg) treatment significantly restored retinal function (a higher amplitude of b-wave in dark-adaptation 3.0 and OPs2 wave) and prevented the decrease of retinal thickness including inner nuclear layer (INL), outer nuclear layer (ONL), and entire retina. Additionally, FSM dramatically decreased VEGF-α, GFAP, and VCAM-1 expressions in retinal tissues. Moreover, FSM notably improved serum antioxidative enzymes glutathione peroxidase, superoxide dismutase, and catalase activities, whereas it reduced serum advanced glycation end products, methane dicarboxylic aldehyde, nitric oxide, and total cholesterol and triglycerides levels. Significance. FSM could ameliorate diabetic rat retina damage possibly via inhibiting inflammation and improving antioxidation.


2014 ◽  
Vol 6 (12) ◽  
pp. 625 ◽  
Author(s):  
Pugazhenthan Thangaraju ◽  
Amitava Chakrabarti ◽  
Dibyajyoti Banerjee ◽  
Debasish Hota ◽  
Tamilselvan ◽  
...  

Biomedika ◽  
2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Ira Cinta Lestari

ABSTRAKDaun mahkota dewa (Phaleria macrocarpa) diketahui memiliki efek anti hiperglikemik dengan menghambat aktivitas enzim pencerna karbohidrat a-glucosidase, namun efeknya pada kondisi diabetes belum diketahui. Penelitian ini bertujuan untuk mengetahui efek antidiabetik ekstrak etanol daun mahkota dewa (EEDMD) terhadap berat badan dan kadar glukosa darah tikus model diabetes. Studi eksperimental dengan rancangan post test only control group design dilakukan terhadap subjek 45 ekor tikus Sprague Dawley. Subjek dikelompokkan dalam kontrol normal, kontrol diabetes diberi pelarut dan diabetes diberi 7mg/200g, 14mg/200g, and 28mg/200g  EEDMD secara peroral, sekali sehari selama 3, 14 dan 25 hari. Model tikus diabetes dibuat dengan injeksi streptozotosin dan nicotinamide. Hasil analisa statistik berat badan dan kadar glukosa puasa antar kelompok terdapat perbedaan yang signifikan. Sehingga kesimpulan penelitian ini adalah pemberian EEDMD memiliki efek antidiabetik pada tikus diabetes yang dinduksi stretozotosin.Kata kunci: Diabetes Mellitus, Phaleria Macrocarpa, Ekstrak Etanol, Streptozotosin, Antidiabetik ABSTRACTPhaleria macrocarpa leaf has been known to have anti-hyperglycemic effects by inhibiting the activity of a-glucosidase carbohydrates digestive enzyme, but the systemic effect on diabetic condition is unknown yet. This study was conducted to investigate the antidiabetic effect of ethanolic extract of Phaleria macrocarpa leaf (EEPML) on body weight and blood glucose levels of diabetic rat model. This was a quasi experimental study with post test only control group design. Fourty five male Sprague Dawley rats were classified into normal control group, diabetic control group with solvent, diabetic with 7mg/200g, 14mg/200g, and 28mg/200g of EEPML peroral administration, once a day for 3, 14 and 25 days. The diabetic rat model was made by streptozotocin and nicotinamide injection. Results : Statistical analysis of mean body weight and fasting blood glucose level showed there were significant differences between treatment groups. Conclusion : Administration of EEPML is able to affect the body weight and blood glucose level of diabetic rat model. Keywords: Diabetes Mellitus, Phaleria Macrocarpa, Ethanolic Extract, Streptozotocin, Antidiabetic


1986 ◽  
Vol 32 (12) ◽  
pp. 967-969
Author(s):  
L. E. Bryan ◽  
T. Schollaardt ◽  
C. Y. Pak ◽  
C. J. Kim ◽  
J. W. Yoon

Purified lipopolysaccharide of Escherichia coli produced specific antibody when injected intraperitoneally or given to rats orally. Either route of immunization did not prevent ascending pyelonephritis in a diabetic rat model. The use of purified LPS excludes the potential contribution of other virulence factors of E. coli as protective antigens in the prevention of ascending pyelonephritis and confirms that anti-lipopolysaccharide antibody is not protective for ascending pyelonephritis.


Sign in / Sign up

Export Citation Format

Share Document