Lack of protection against ascending Escherichia coli pyelonephritis in diabetic rats following immunization with purified lipopolysaccharide

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.

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Neuropeptides (Substance P) Localisation in the Peripheral Nervous System and Skin in a Diabetic Rat Model: A Possible Mechanism for Acceleration Wound Healing in Diabetic Rats

Journal of Cytology & Histology ◽

10.4172/2157-7099.1000510 ◽

2018 ◽

Vol 09 (04) ◽

Author(s):

Seham A Abd El-Aleem ◽

Edward B Jude

Keyword(s):

Wound Healing ◽

Nervous System ◽

Substance P ◽

Peripheral Nervous System ◽

Rat Model ◽

Diabetic Rats ◽

Diabetic Rat ◽

Diabetic Rat Model

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Nicotine Exposure Exacerbates Development of Cataracts in a Type 1 Diabetic Rat Model

Experimental Diabetes Research ◽

10.1155/2012/349320 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Nima Tirgan ◽

Gabriela A. Kulp ◽

Praveena Gupta ◽

Adam Boretsky ◽

Tomasz A. Wiraszka ◽

...

Keyword(s):

Rat Model ◽

Serum Levels ◽

Diabetic Rats ◽

Diabetic Rat ◽

Positive Trend ◽

Sprague Dawley ◽

Nicotine Treatment ◽

Sprague Dawley Rats ◽

Diabetic Rat Model

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.

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Fushiming Capsule Attenuates Diabetic Rat Retina Damage via Antioxidation and Anti-Inflammation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5376439 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Mengshan He ◽

Pan Long ◽

Lunfeng Guo ◽

Mingke Zhang ◽

Siwang Wang ◽

...

Keyword(s):

Rat Model ◽

Day Treatment ◽

Outer Nuclear Layer ◽

Diabetic Rats ◽

Retinal Function ◽

Diabetic Rat ◽

Full Field ◽

Rat Retina ◽

Protein Levels ◽

Diabetic Rat Model

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.

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

PLoS ONE ◽

10.1371/journal.pone.0262396 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262396

Author(s):

Ji-Yeon Lee ◽

Mirinae Kim ◽

Su Bin Oh ◽

Hae-Young Kim ◽

Chongtae Kim ◽

...

Keyword(s):

Superoxide Dismutase ◽

Diabetic Retinopathy ◽

Rat Model ◽

Treated Group ◽

Diabetic Rats ◽

Photopic Negative Response ◽

Diabetic Rat ◽

Control Group ◽

Inner Plexiform Layer ◽

Diabetic Rat Model

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.

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Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling

Journal of Diabetes Research ◽

10.1155/2019/4875421 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Lingli Long ◽

Yubin Li ◽

Shuang Yu ◽

Xiang Li ◽

Yue Hu ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Oral Administration ◽

Rat Model ◽

Microvascular Dysfunction ◽

Tube Formation ◽

Diabetic Rats ◽

Diabetic Rat ◽

Diabetic Rat Model

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.

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Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model

Marine Drugs ◽

10.3390/md19070360 ◽

2021 ◽

Vol 19 (7) ◽

pp. 360

Author(s):

Shing-Hwa Liu ◽

Fan-Wen Chen ◽

Meng-Tsan Chiang

Keyword(s):

Lipid Peroxidation ◽

Glucose Metabolism ◽

Protein Expression ◽

Rat Model ◽

Diabetic Rats ◽

Diabetic Rat ◽

Chitosan Oligosaccharide ◽

High Fat ◽

Abnormal Glucose Metabolism ◽

Diabetic Rat Model

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.

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Antioxidants Isolated from Elaeagnus umbellata (Thunb.) Protect against Bacterial Infections and Diabetes in Streptozotocin-Induced Diabetic Rat Model

Molecules ◽

10.3390/molecules26154464 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4464

Author(s):

Nausheen Nazir ◽

Muhammad Zahoor ◽

Mohammad Nisar ◽

Imran Khan ◽

Riaz Ullah ◽

...

Keyword(s):

Lipid Peroxidation ◽

Body Weight ◽

Rat Model ◽

Bacterial Infections ◽

Density Lipoprotein ◽

Diabetic Rats ◽

Diabetic Rat ◽

Elaeagnus Umbellata ◽

Diabetic Rat Model

The increase in resistance of microbes against conventional drugs is currently a hot issue, whereas diabetes is another main cause of mortalities encountered throughout the world after cancer and heart attacks. New drug sources in the form of plants are investigated to get effective drugs for the mentioned diseases with minimum side effects. Elaeagnus umbellata Thunb. is a medicinal plant used for the management of stress related disorders like diabetes and other health complications. The active constituents of the chloroform extract derived from E. umbellata berries was isolated by silica gel column chromatography which were identified as morin, phloroglucinol, and 1-hexyl benzene through various spectroscopic techniques (electron ionization mass spectrometry, 1H-NMR, and 13C-NMR spectroscopy). The possible protective effects (antioxidant, antibacterial, and antidiabetic activity) of isolated compounds were evaluated using reported methods. Morin exhibited strong in vitro antiradical potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals along with prominent antibacterial activities against selected bacterial strains (Escherichia coli, Bacillus cereus, Salmonella typhi, Klebsiella pneumonia, Pseudomonas aeruginosa and Proteus mirabilis). Among the isolated compounds the more potent one (morin) was assessed for its in vivo antidiabetic potential in streptozotocin-induced diabetic rat model. The in vivo effects observed were further confirmed in ex vivo experiments where the effect of isolated compound on antioxidant enzyme like glutathione peroxidase (GPx), total content of reduced glutathione (GSH), % DPPH inhibition, and the lipid peroxidation MDA (Malondialdehyde) level in pancreatic tissues homogenates were evaluated. In vivo morin at tested doses (2, 10, 15, 30 and 50 mg/kg body weight) significantly restored the alterations in the levels of fasting blood glucose level and body weight loss along with significant decrease in levels of cholesterol, triglycerides, low density lipoprotein, HbA1c level, and significantly increased the high-density lipoprotein in diabetic rats. Morin also effectively ameliorated the hepatic enzymes, and renal functions like serum creatinine. Morin significantly increased the antioxidant enzyme like GPx activity, GSH content, and % DPPH inhibition activity, while reduced the lipid peroxidation MDA (malondialdehyde) level in pancreatic tissues homogenates, and modification of histopathological changes in diabetic rats. Morin exhibited high antioxidant, antibacterial, and antidiabetic potentials as compared to phloroglucinol and 1-hexyl benzene, that could, therefore, be considered as a promising therapeutic agent to treat diabetes mellitus and bacterial infections.

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Exploration of the Effect and Mechanism of ShenQi Compound in a Spontaneous Diabetic Rat Model

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190225113859 ◽

2019 ◽

Vol 19 (5) ◽

pp. 622-631 ◽

Cited By ~ 3

Author(s):

Ya Liu ◽

Jian Kang ◽

Hong Gao ◽

Xiyu Zhang ◽

Jun Chao ◽

...

Keyword(s):

Blood Glucose ◽

Signaling Pathway ◽

Rat Model ◽

Mtor Signaling ◽

Diabetic Rat ◽

Gene Microarray ◽

Mtor Signaling Pathway ◽

Glucose Fluctuation ◽

Blood Glucose Fluctuation ◽

Diabetic Rat Model

Background: Type 2 Diabetes Mellitus (T2DM) is a world-wide metabolic disease with no cure from drugs and treatment. In China, The Traditional Chinese Medicine (TCM) herbal formulations have been used to treat T2DM for centuries. Methods: In this study, we proposed a formula called ShenQi Compound (SQC), which has been used in clinical therapeutics in China for several years. We evaluated the effect of SQC in a spontaneous diabetic rat model (GK rats) by detecting a series of blood indicators and performing histological observations. Meanwhile, the gene microarray and RT-qPCR experiments were used to explore the molecular mechanism of SQC treatment. In addition, western medicine, sitagliptin was employed as a comparison. Results: The results indicated that SQC and sitagliptin could effectively improve the serum lipid (blood Total Cholesterol (TC) and blood Triglycerides (TG)), hormone levels (serum insulin (INS), Glucagon (GC) and Glucagon-Like Peptide-1 (GLP-1)), alleviated the inflammatory response (hypersensitive C-Reactive Protein (hsCRP)), blood glucose fluctuation (Mean Blood Glucose (MBG), standard deviation of blood glucose (SDBG) and Largest Amplitude of plasma Glucose Excursions (LAGE)), pancreatic tissue damage and vascular injury for T2DM. Compared with sitagliptin, SQC achieved a better effect on blood glucose fluctuation (p<0.01). Meanwhile, the gene microarray and RT-qPCR experiments indicated that SQC and sitagliptin may improve the T2DM through affecting the biological functions related to apoptosis and circadian rhythm. Moreover, SQC might be able to influence the mTOR signaling pathway by regulating Pik3r1, Ddit4 expression. Conclusion: All these results indicate that SQC is an effective therapeutic drug on T2DM. Notably, SQC presents an obvious blood glucose fluctuation-preventing ability, which might be derived from the regulation of the mTOR signaling pathway.

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