scholarly journals Inhibition of HMGB1 Promotes Osseointegration under Hyperglycemic Condition through Improvement of BMSC Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Beilei Liu ◽  
Xueqi Gan ◽  
Yuwei Zhao ◽  
Hongdou Yu ◽  
Jing Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Mobility ◽  
Diabetic Rats ◽  
Titanium Implants ◽  
Sprague Dawley ◽  
Normal Glucose ◽  
Ct Analysis ◽  
Stress Damage

High mobility group box 1 (HMGB1) participates actively in oxidative stress damage and the latter relates closely to diabetic complications, including poor implant osseointegration. This article is aimed at investigating the effects of HMGB1 on dysfunction of bone marrow stromal cells (BMSCs) and impaired osseointegration under diabetic environment. In vitro, BMSCs were treated with normal glucose (NG), high glucose (HG), and HG+glycyrrhizin (HMGB1 inhibitor, HG+GL). Cell proliferation, osteogenic behaviors, and oxidative stress were determined. In vivo, 8-week-old Sprague-Dawley rats were categorized to control, streptozotocin-induced diabetic, and diabetic-GL groups. Rats received GL (50 mg/kg, i.p.) or vehicle treatment daily after titanium implants were planted into the tibiae. After 4 and 8 weeks, plasma lipoperoxide detection, μCT analysis, and histomorphometric evaluation were conducted. By these approaches, we demonstrated that inhibiting HMGB1 by GL significantly attenuated HG-induced upregulation of HMGB1, HMGB1 ligand receptor for advanced glycation end products (RAGE) and their interaction, relieved oxidative stress, and reversed the downregulation of osteogenic markers, resulting in improved osteogenic differentiation. In diabetic rats, GL administration suppressed the upregulation of HMGB1, attenuated the lipoperoxide, and ameliorated the impaired trabecular structure and osseointegration. Taken together, inhibiting HMGB1 can be an effective approach to relieve BMSC dysfunction and enhance osseointegration under diabetic environment.

scholarly journals The Effects of Low-dose Empagliflozin on Cardiac Function in a Rat Model of Streptozotocin-induced Diabetes

2021 ◽  
Author(s):  
Zeynep Eilf Yesilyurt ◽  
Irem Karaomerlioglu ◽  
Betül Rabia Erdogan ◽  
Gaye Ozturk ◽  
Martin C Michel ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Low Dose ◽  
Contractile Response ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Stroke Work ◽  
Sprague Dawley ◽  
Loop Analysis

Abstract Purpose: Diabetes mellitus is a metabolic disorder leading to cardiovascular complications. Both in vivo cardiac function and β-adrenoceptor (β-AR) mediated responsiveness have been demonstrated to be blunted in the diabetic heart. Sodium glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) have shown cardioprotective effects in patients and in some animal models. In this study, we aimed to investigate the effects of low-dose EMPA (10 mg/kg/day) on in vivo cardiac function and β-AR-mediated contractile response in streptozotocin (STZ)-induced diabetic rats. Methods: 11-12 week old male Sprague Dawley rats were divided into 4 groups; control, EMPA-treated control, diabetic, EMPA-treated diabetic. Diabetes was induced by STZ injection (40 mg/kg, i.p.). After 13-16 weeks, some of the diabetic and control rats were treated with a low dose of EMPA (10 mg/kg/day, oral gavage, once a day) or vehicle for another 8 weeks. At study end, in vivo cardiac function was evaluated by pressure-volume loop analysis. β-AR mediated contractile response was determined using isoprenaline in papillary muscle preparations. Results: EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, +dp/dt and -dp/dt and increased isovolumic relaxation, whereas in vitro responses were reduced to a minor extent. Treatment with EMPA showed a trend for improvement of some but not all parameters. Conclusion: Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment although it reduced blood glucose. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

scholarly journals Inhibitory Effects of Raw-Extract Centella asiatica (RECA) on Acetylcholinesterase, Inflammations, and Oxidative Stress Activities via In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 892 ◽  
Author(s):  
Zetty Zulikha Hafiz ◽  
Muhammad ‘Afif Mohd Amin ◽  
Richard Muhammad Johari James ◽  
Lay Kek Teh ◽  
Mohd Zaki Salleh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Centella Asiatica ◽  
Raw 264.7 Cells ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Sprague Dawley Rats ◽  
And Oxidative Stress

Centella asiatica (C. asiatica) is one of the medicinal plants that has been reported to exert comprehensive neuroprotection in vitro and in vivo. In view of this, the present study was performed to investigate the effect of ethanolic extract of C. asiatica, designated as raw-extract of C. asiatica (RECA) in reducing the acetylcholinesterase (AChE), inflammations, and oxidative stress activities via both in vitro (SH-SY5Y and RAW 264.7 cells) and in vivo (Sprague Dawley rats). Quantitative high-performance liquid chromatography analysis reveals that RECA contains a significantly high proportion of glycosides than the aglycones with madecassoside as the highest component, followed by asiaticoside. Treatment of SH-SY5Y cells with RECA significantly reduced the AChE activity in a concentration-dependent manner with an IC50 value of 31.09 ± 10.07 µg/mL. Furthermore, the anti-inflammatory and antioxidant effects of RECA were evaluated by lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. Our results elucidated that treatment with RECA significantly suppressed the level of pro-inflammatory cytokine/mediators and oxidative stress released in a concentration-dependent manner. Interestingly, these patterns of inhibition were consistent as observed in the LPS-induced neuroinflammation Sprague Dawley rats’ model. The highest concentration used in the two models presented the most significant results. Herein, our findings strongly suggest that RECA may offer therapeutic potential for the treatment of Alzheimer’s disease through inhibiting the AChE, inflammation, and oxidative stress activities.

scholarly journals Inhibition of gap junction composed of Cx43 prevents against acute kidney injury following liver transplantation

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Dongdong Yuan ◽  
Xiaoyun Li ◽  
Chenfang Luo ◽  
Xianlong Li ◽  
Nan Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Organ Protection ◽  
Cx43 Expression

Abstract Postoperative acute kidney injury (AKI) is a severe complication after liver transplantation (LT). Its deterioration and magnification lead to the increase in mortality. Connexin43 (Cx43) mediates direct transmission of intracellular signals between neighboring cells, always considered to be the potent biological basis of organ damage deterioration and magnification. Thus, we explored the effects of Cx43 on AKI following LT and its related possible mechanism. In this study, alternations of Cx43 expression were observed in 82 patients, receiving the first-time orthotopic LT. We built autologous orthotopic liver transplantation (AOLT) models with Sprague–Dawley (SD) rats in vivo, and hypoxia-reoxygenation (H/R) or lipopolysaccharide (LPS) pretreatment models with kidney tubular epithelial cells (NRK-52E) in vitro, both of which were the most important independent risk factors of AKI following LT. Then, different methods were used to alter the function of Cx43 channels to determine its protective effects on AKI. The results indicated that patients with AKI suffering from longer time of tracheal intubation or intensive care unit stay, importantly, had significantly lower survival rate at postoperative 30 days and 3 years. In rat AOLT models, as Cx43 was inhibited with heptanol, postoperative AKI was attenuated significantly. In vitro experiments, downregulation of Cx43 with selective inhibitors, or siRNA protected against post-hypoxic NRK-52E cell injuries caused by H/R and/or LPS, while upregulation of Cx43 exacerbated the above-mentioned cell injuries. Of note, alternation of Cx43 function regulated the content of reactive oxygen species (ROS), which not only mediated oxidative stress and inflammation reactions effectively, but also regulated necroptosis. Therefore, we concluded that Cx43 inhibition protected against AKI following LT through attenuating ROS transmission between the neighboring cells. ROS alternation depressed oxidative stress and inflammation reaction, which ultimately reduced necroptosis. This might offer new insights for targeted intervention for organ protection in LT, or even in other major surgeries.

scholarly journals Antioxidant Treatment Reverts Increased Arterial Basal Tone and Oxidative Stress in Nephrectomized (5/6) Hypertensive Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Rodrigo O. Marañón ◽  
Claudio Joo Turoni ◽  
Maria Sofia Karbiner ◽  
Nicolas Salas ◽  
Maria Peral de Bruno
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Basal Tone ◽  
No Bioavailability

Nonischemic 5/6 nephrectomized rat (NefR) is a model of chronic kidney disease. However, little is known about vascular dysfunction and its relation with hypertension in NefR.Aims. To evaluate possible alterations of endothelial function, NO-bioavailability, and basal tone in aorta from NefR and the role of oxidative stress. Sprague Dawley rats were divided into sham rats (SR), NefR, and NefR treated with tempol (NefR-T). Mean arterial pressure (MAP) and renal function were determined. In isolated aortic rings the following was measured: 1-endothelial function, 2-basal tone, 3-NO levels, 4-membrane potential (MP), and 5-oxidative stress. NefR increased MAP (SR: 119 ± 4 mmHg;n=7; NefR: 169 ± 6;n=8;P<0.001). Tempol did not modify MAP (NefR-T: 168 ± 10;n=6;P<0.001). NefR showed endothelial dysfunction, increased basal tone and decreased NO levels (SR: 32 ± 2 nA;n=7, NefR: 10 ± 2;n=8;P<0.001). In both in vitro and in vivo tempol improves basal tone, NO levels, and MP. Oxidative stress in NefR was reverted in NefR-T. We described, for the first time, that aorta from NefR presented increased basal tone related to endothelial dysfunction and decreased NO-bioavailability. The fact that tempol improves NO-contents and basal tone, without decrease MAP, indicates that oxidative stress could be implicated early and independently to hypertension, in the vascular alterations.

Chronic tempol treatment attenuates the renal hemodynamic effects induced by a heme oxygenase inhibitor in streptozotocin diabetic rats

2011 ◽  
Vol 301 (5) ◽  
pp. R1540-R1548 ◽  
Author(s):  
Francisca Rodriguez ◽  
Bernardo Lopez ◽  
Cayetano Perez ◽  
Francisco J. Fenoy ◽  
Isabel Hernandez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Heme Oxygenase ◽  
Oral Treatment ◽  
Diabetic Rats ◽  
Renal Hemodynamics ◽  
Heme Oxygenase 1 ◽  
Acute Administration ◽  
Sprague Dawley

Heme oxygenase-1 (HO-1) is induced by oxidative stress and plays an important role in protecting the kidney from oxidant-mediated damage in the streptozotocin (STZ) rat model of type-1 diabetes mellitus (DM-1). HO-derived metabolites, presumably carbon monoxide (CO), mediate vasodilatory influences in the renal circulation, particularly in conditions linked to elevated HO-1 protein expression or diminished nitric oxide (NO) levels. We tested the hypothesis that diabetes increases oxidative stress and induces HO-1 protein expression, which contributes to regulate renal hemodynamics in conditions of low NO bioavailability. Two weeks after the induction of diabetes with STZ (65 mg/kg iv), Sprague-Dawley rats exhibited higher renal HO-1 protein expression, hyperglycemia, and elevated renal nitrotyrosine levels than control normoglycemic animals. In anesthetized diabetic rats, renal vascular resistance (RVR) was increased, and in vivo cortical NO levels were reduced ( P < 0.05) compared with control animals. Acute administration of the HO inhibitor Stannous mesoporphyrin (SnMP; 40 μmol/kg iv) did not alter renal hemodynamics in control rats, but greatly decreased glomerular filtration rate and renal blood flow, markedly increasing RVR in hyperglycemic diabetic rats. Chronic oral treatment with the SOD mimetic tempol prevented the elevation of nitrotyrosine, the HO-1 protein induction, and the increases in RVR induced by SnMP in the diabetic group, without altering basal NO concentrations or RVR. Increasing concentrations of a CO donor (CO-releasing molecule-A1) on pressurized renal interlobar arteries elicited a comparable relaxation in vessels taken from control or diabetic animals. These results suggest that oxidative stress-induced HO-1 exerts vasodilatory actions that partially maintain renal hemodynamics in uncontrolled DM-1.

scholarly journals Persea americana Leaf Ethyl Acetate Extract Phytochemical, In-vitro Antioxidant and In-vivo Potentials to Mitigate Oxidative Stress in Alloxan-induced Hyperglycaemic Rats

2019 ◽  
pp. 1-11
Author(s):  
J. A. Mashi ◽  
A. M. Sa’id ◽  
R. I. Idris ◽  
I. Aminu ◽  
A. A. Muhammad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Ethyl Acetate ◽  
Ethyl Acetate Extract ◽  
Diabetic Rats ◽  
Persea Americana ◽  
Albino Rats ◽  
Standard Drug

The purpose of this study was to investigate the in-vivo and in-vitro potentials of ethyl acetate extract of P. americana leaf in alloxan-induced diabetic rats. Quantitative phytochemicals analyzed includes; flavonoids, saponins, tannins, alkaloids and phenolics. Measurement of antioxidant activity using 1,1-Diphenyl-2-picrylhydrazyl, total antioxidant capacity, hydroxyl radical, hydrogen peroxide, superoxide radical and ferric reducing activity of the extract was carried out. Hyperglycemia was induced by intraperitoneal injection of alloxan monohydrate to albino rats. In-vivo anti-oxidant potentials of the extract were evaluated by measuring liver homogenate activity of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and malondyaldehyde in alloxan-induced diabetic rats administered with the extract.  A total of 30 Albino rats were used for this experiment and they were divided into six groups of 5 rats each. Group A; normal control, Group B; diabetic control, Groups C-E; experimental groups administered with different doses (100, 200 and 400 mg/kg body weight respectively); of the extract and Group F; glucophage (84 mg/kg body weight, standard drug) for 4 weeks. This study was conducted in the Department of Biochemistry, Bayero University, Kano, in August, 2018. Data was analyzed using one-way ANOVA with P=.05 value considered as significant. Results of the quantitative phytochemical investigation shows that the extract is rich in phenolics (184.1±0.6), flavonoids (115.8±2.1), alkaloids (41.5±1.8), with least concentration of tannis (21.2±0.8) and saponins (15.2±2.3). The extract exhibited high radical scavenging activity against synthetic free radicals (DPPH), reactive oxygen species (peroxide, superoxide and hydroxyl acid) and high ability to reduce Fe3+ to Fe2+ (FRAP). The activities of antioxidant enzymes of the treated rats were increased significantly (P=.05) while the level malondyaldehyde was significantly decreased (P=.05) in the treated groups. Ethyl acetate leaf extract of Persea americana contains phytochemical substances which improved antioxidant status and can be use as herbal therapy for the management of oxidative stress induced by diabetes mellitus and associated complications.

Soluble and particulate phenylethanolamine N-methyltransferase in hypothalamus of diabetic rats

1992 ◽  
Vol 263 (2) ◽  
pp. E335-E339
Author(s):  
J. E. Chappell ◽  
J. K. Stewart
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Particulate Fraction ◽  
Sprague Dawley ◽  
Rat Hypothalamus ◽  
Tissue Extracts ◽  
Sprague Dawley Rats ◽  
In Vitro Response

Experimental diabetes increases total phenylethanolamine N-methyltransferase (PNMT) activity in the medulla-pons but not in the hypothalamus. In this study diabetes was induced with streptozotocin (65 mg/kg) in male Sprague-Dawley rats. Twenty-eight days after treatment there were no differences in soluble PNMT activity in the hypothalamus of diabetics and controls, but PNMT activity in a membrane-associated (particulate) fraction of hypothalamus was evaluated approximately twofold in tissues of diabetic animals compared with controls. A specific PNMT inhibitor, incubated with tissue extracts of control rats, abolished greater than 90% of particulate PNMT activity in the hypothalamus but reduced soluble PNMT activity in the hypothalamus by only 47%. These findings indicate that membrane-associated PNMT activity in rat hypothalamus differs from soluble hypothalamic PNMT in the in vitro response to an inhibitor and the in vivo response to diabetes and suggest the importance of separating subcellular hypothalamic fractions prior to assay of PNMT.

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