Possible role of Dickkopf-1 protein in the pathogenesis of tympanosclerosis in a rat model

2017 ◽  
Vol 131 (10) ◽  
pp. 860-865
Author(s):  
Y Zhang ◽  
S Wang ◽  
Y Zheng ◽  
A Liu
Keyword(s):  
Middle Ear ◽  
Morphological Changes ◽  
Control Group ◽  
Sprague Dawley ◽  
Middle Ear Mucosa ◽  
Inflammatory Infiltration ◽  
Sprague Dawley Rats ◽  
Sclerotic Lesions ◽  
Tympanic Membranes

AbstractObjectives:This study aimed to investigate the expression of DKK1 protein in an experimental model of tympanosclerosis and its possible role in the pathogenesis of this disorder.Methods:Forty Sprague Dawley rats were included in the study: 20 in the control group (which received no treatment) and 20 in the experimental group (which received an incision to induce tympanosclerosis). Otomicroscopy was performed to observe the development of myringosclerosis. Haematoxylin and eosin staining was performed to observe the morphological changes. Western blot analysis and immunohistochemistry were performed to assess the expression of DKK1 protein.Results:At day 15, sclerotic lesions were observed in 70 per cent of the tympanic membranes. Inflammatory infiltration and hyaline degeneration markedly appeared in the tympanic membranes and middle-ear mucosa. DKK1 protein was mainly distributed in the cytoplasm of epithelial cells, which were widely distributed in the tympanic membranes and middle-ear mucosa. The expression of DKK1 protein was significantly decreased in the calcified experimental ears.Conclusion:DKK1 protein is involved in the pathogenesis of tympanosclerosis by regulating the Wnt/β-catenin signalling pathway.

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

2021 ◽  
Author(s):  
Atta Mohammad Dost ◽  
Mehmet Gunata ◽  
Onural Ozhan ◽  
Azibe Yildiz ◽  
Nigar Vardi ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Kidney Tissue ◽  
Control Group ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Per Oral

Abstract Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p < 0.05). However, this improvement was not detected biochemically. These results show that CAR treatment before and after AK improves nephrotoxicity in the histopathological level.

scholarly journals The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats

2017 ◽  
Vol 42 (1) ◽  
pp. 231-241 ◽  
Author(s):  
Wanhui Lin ◽  
Wenli Huang ◽  
Shenggen Chen ◽  
Mingxing Lin ◽  
Qingyu Huang ◽  
...  
Keyword(s):  
Mossy Fiber ◽  
Inhibitory Effect ◽  
Primary Objective ◽  
Control Group ◽  
Sprague Dawley ◽  
Mossy Fiber Sprouting ◽  
Male Adult ◽  
Sprague Dawley Rats ◽  
Two Stages

Objective: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. Methods: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages. The first stage involves equally dividing 36 epileptic rats into three groups with treatments of none, 5-HTR6 antagonist SB-27104 (SB) and vehicle DMSO. Then behavior and electroencephalogram (EEG) of rats were monitored by video-EEG. The second stage involves dividing 126 epileptic rats into seven groups with treatments of none, 10% DMSO, SB (100 µg/kg), Fyn antagonist PP2 (50 µg/kg), p-ERK1/2 antagonist PD-98059 (30 µg/kg), SB (100 µg/ kg) + PP2 (50 µg/kg); SB (100 µg/kg) + PD-98059 (30 µg/kg). We also treated 18 rats in the control group of the first stage with 100 µg/kg 5-HTR6 agonist WAY-181187 (WAY). MFS of rats was detected through the approach of Timm’s staining. Finally, expressions of 5-HTR6, Fyn, p-ERK1/2 and GAP-3 were qualified and semi-quantified via western blotting or RT-PCR. Results: Induction of SE could stimulate formation of MFS and increased GAP-43 expressions. Expressions of 5-HTR6, Fyn and p-ERK1/2 were also up-regulated with increasing time after establishment of SE models. The development of MFS was remarkably inhibited by SB, PP2 and PD. Compared to the single antagonist, such an inhibitory effect was enhanced by SB+PD or SB+PP. Moreover, treatment of healthy rats with WAY would contribute to up-regulated Fyn and p-ERK1/2 expressions, as well as development of MFS (P < 0.05). Suppression of Fyn triggered a down-regulating trend of p-ERK1/2 (P < 0.05), however, suppressed p-ERK1/2 did not have such a significant effect on Fyn expression. Conclusion: HTR6 may affect the progression of MFS by activating both p-ERK1/2 and Fyn, which further modulate the expression of GAP-43.

The ultrastructure of rat jejunal enterocytes after colchicine application

1978 ◽  
Vol 36 (2) ◽  
pp. 538-539
Author(s):  
M. Pavelka ◽  
L. Stockinger
Keyword(s):  
Sodium Phosphate ◽  
Control Group ◽  
Sprague Dawley ◽  
Ultrastructural Studies ◽  
Sprague Dawley Rats ◽  
Lipid Particle ◽  
Electron Microscopical ◽  
Experimental Group ◽  
Colchicine Application

In jejunal enterocytes microtubules (mts) have been supposed to be involved in mechanisms of lipid particle transport. To elucidate the role of mts in this context detailed ultrastructural studies of rat jejunal enterocytes after application of the microtubule-inhibiting substance colchicine have been performed.Material and Methods: Female Sprague-Dawley rats having been fasted for 24 hours received 0. 5 mg colchicine per 100 g body weight dissolved in 1. 0 ml of 0. 9% NaCl (experimental group) or 1. 0 ml of 0. 9% NaCl (control group) intraperitoneally. Segments of the upper jejunum were excised 11/2, 23, 4 and 6 hours later and prepared for electron- microscopical observation (Fixation:2. 5% sodium phosphate buffered glutaraldehyde, pH 7. 2; Postfixation: 1% veronalacetate buffered OsO4; Embedding in Epon; Staining with alcoholic uranylacetate and alkaline lead citrate).Results: The ultrastructural alterations after colchicine application concern predominantly mts and Golgi apparatus and are apparent already 11/2 hours after colchicine application.

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B

2018 ◽  
Vol 38 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Z-D Li ◽  
J Luo ◽  
L-H Jia ◽  
X-Y Wang ◽  
Z-K Xun ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Polymyxin B ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
C 30 ◽  
C 50

The receptor megalin plays an important role in the accumulation of polymyxin B (PMB) in renal cells in vitro. This study aimed to examine the effects of cytochrome c (cyto c), a typical megalin ligand, on renal accumulation and nephrotoxicity of PMB in vivo. Thirty Sprague-Dawley rats were randomly divided into the vehicle control group, PMB group, PMB + cyto c 50, 100, or 200 mg/kg group, respectively, and were treated with intravenous cyto c 30 min before the administration of PMB 4.0 mg/kg once a day for consecutive 5 days. On the 4th day after administration, 24 h urine was collected to determine N-acetyl-β-D-glucosaminidase excretion. Six hours after the last injection on the 5th day, kidneys were harvested to assay PMB concentration and observe pathological alterations, and blood samples were collected to assay serum creatinine (SCr), blood urea nitrogen (BUN), and blood β2-microglobulin (β2-MG) levels. Cyto c 50, 100, and 200 mg/kg decreased the accumulation of PMB in the kidney by 18.5%, 39.1% ( p < 0.01), and 36.8% ( p < 0.01), respectively, and reduced 24 h N-acetyl-β-D- glucosaminidase excretion by 22.5% ( p < 0.05), 40.4% ( p < 0.01), and 40.4% ( p < 0.01), respectively. Kidney pathological damage induced by PMB was markedly reduced by cyto c 100 mg/kg and 200 mg/kg. However, there were no significant differences in SCr, BUN, and blood β2-MG levels among the groups. These results indicated that cyto c may inhibit the renal accumulation and nephrotoxicity of PMB in a rat model, further proving the role of megalin in the accumulation of PMB.

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries. Role of oxidative stress

2021 ◽  
Author(s):  
Ivana Jukic ◽  
Zrinka Mihaljevic ◽  
Anita Matic ◽  
Martina Mihalj ◽  
Natasa Kozina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Arteries ◽  
Control Group ◽  
Ros Production ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Losartan Group

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-weeks old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilations was compared to control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) and cyclooxygenase inhibitor indomethacin (INDO) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by INDO only at ∆100 mmHg, whereas L-NAME had no effect. In losartan group, TEMPOL (a superoxide scavenger) restored dilatation, while TEMPOL+L-NAME together significantly reduced FID compared to restored dilatation with TEMPOL alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared to control group, while flow increased the NO and ROS production in losartan group and had no effect in control group. In losartan group, TEMPOL decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of AngII, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.

Abstract 11029: Netrin-1 Alleviates Post-Resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lu Yin ◽  
Shen Zhao ◽  
JoongBum Moon ◽  
Peng Sun ◽  
Jiangang Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Saline Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group 2

Introduction: Post-resuscitation myocardial dysfunction has been recognized as one of the major causes of fatal outcomes after initial successful cardiopulmonary resuscitation (CPR). Previous research demonstrated that Netrin-1 improved post ischemic injury cardiac function via preservation of mitochondrial integrity. In the present study, we investigated the role of netrin-1 after cardiac arrest. Hypothesis: We hypothesized that the netrin-1 alleviated post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Methods: A total of sixteen male Sprague-Dawley rats (450-550 g) were randomized to two groups as follows: (1) Control group (C group); (2) Netrin-1 group (N group). Ventricular fibrillation was induced and untreated for 8 mins followed by 8 mins of CPR. Netrin-1 or saline were given at the onset of precordial compression. Ejection fraction (EF) was measured by echocardiography at baseline, 1,2,3 and 4 hours after ROSC. Results: Eight rats were resuscitated in the netrin-1 group and 7 rats were resuscitated in the saline group. In both groups, EF decreased after resuscitation when compared to the baseline (#p < 0.05). In the netrin-1 group, EF decreased from ( 68.1±3.4)% at baseline to (51.1±5.0)% at 1 hour post-resuscitation. In the saline group, EF decreased from (67.7±2.1)% at baseline to (44.5±5.3)% at 1 hr post-resuscitation. EF was better in the netrin-1 group than in the saline group at 2, 3 and 4 hours post-resuscitation (*p < 0.05) ( Figure 1). Conclusion: Netrin-1 alleviates post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.

scholarly journals Leptin induces the expression of tumorigenic genes in the gastric mucosa of male Sprague-Dawley rats

2018 ◽  
Vol 243 (14) ◽  
pp. 1118-1124 ◽  
Author(s):  
Faizatul Isyraqiah ◽  
Methil K Kutty ◽  
Damayanthi Durairajanayagam ◽  
Norita Salim ◽  
Harbindarjeet Singh
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Gastric Carcinogenesis ◽  
Control Group ◽  
Sprague Dawley ◽  
Gastric Cancer Cells ◽  
Sprague Dawley Rats

Leptin promotes the growth of gastric cancer cells in vitro. It is, however, unknown if leptin induces gastric cancer in vivo. This study therefore investigated the effect of leptin on the histology and expression of tumorigenic genes in the stomach of rats following 40 weeks of leptin treatment. Male Sprague-Dawley rats, aged 6 weeks, were randomized into control and experimental groups ( n = 8 per group). The experimental group was given intraperitoneal injections of leptin (60 µg/kg/day) once daily for 40 weeks, whereas the control group received intraperitoneal injection of an equal volume of normal saline daily. Rats were housed in polypropylene cages for the duration of the study. Body weight was measured weekly. Upon completion of treatment, rats were euthanized and their stomachs were collected for histopathological examination, microarray, and RT-qPCR. Data were analyzed using one-way ANOVA and Fisher’s exact test. On histology, one rat (12.5%) in the leptin-treated group had a large red-colored tumor nodule at the pyloric antrum of the stomach. Microscopically, stomachs of two leptin-treated rats (25%) showed hyperplasia or dysplasia. Microarray analysis revealed significant upregulation of a number of genes in the stomachs of leptin-treated rats that have been shown to be associated with tumorigenesis in other tissues, including Furin (protein maturation), Eef1a1 and Eif4g2 (translation factors), Tmed2 (vesicular trafficking), Rab7a (plasma membrane trafficking), Rfwd2 (protein degradation), Fth1 and Ftl1 (oxygen transport), Tspan8, Tspan1, Fxyd3, and Rack1 (cell migration), Pde4d (signal transduction), Nupr1 and Ybx1 (transcription factors), Ptma and Tmem134 (oncogenes), Srsf2 (mRNA maturation), and Reep5 (cell proliferation). None of the known oncogenes were, however, significantly up-regulated. In conclusion, although the overall effect of leptin on gastric carcinogenesis seems inconclusive, the findings of dysplasia and the up-regulation of some of the cancer-related genes nevertheless warrant further scrutiny on the role of leptin in gastric cancer. Impact statement Gastric cancer is the third most common cause of death due to cancer in the world. Obese individuals are at risk of developing gastric cancer, and the reason for this is unknown. Serum leptin levels are high in obese individuals and leptin is known to induce proliferation of gastric cancer cells in vitro. However, to date, no reports exist on the tumorigenic effects of leptin on the stomach in vivo. This study therefore determines if chronic leptin administration induces gastric carcinogenesis in non-obese rats, which might serve as a useful animal model for future studies. Although the findings are somewhat inconclusive, to our knowledge, however, this is the first study to show the up-regulation of numerous potential driver genes that highlight the potential role of leptin in the higher prevalence of gastric cancer among obese individuals. The findings certainly necessitate further scrutiny of leptin gastric cancer.

scholarly journals Repeated administration of fenitrothion alters renal functions via oxidative stress mechanism without inhibiting acetylcholinesterase activity in rats

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Nur Afizah Yusoff ◽  
Izzah Irdina Juremi ◽  
Siti Balkis Budin ◽  
Izatus Shima Taib
Keyword(s):  
Oxidative Stress ◽  
Ache Activity ◽  
Corn Oil ◽  
Morphological Changes ◽  
Protein Carbonyl ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Oxidative Stress Status ◽  
Kidney Functions

Background: The main mechanism of fenitrothion (FNT) toxicity is by inhibiting the acetylcholinesterase enzyme, though studies have shown that FNT might also develop other toxicological manifestations, including oxidative stress. However, the kidney functions as well as oxidative stress status after repeated exposure to FNT is not well documented. Objective: The present study was conducted to evaluate the kidney functions and oxidative stress status after exposure to low doses of FNT. Materials and Methods: 24 male Sprague-Dawley rats were divided randomly into three groups (n = 8/group): control, which received 1 mg/ml corn oil; FNT 10, which received 10 mg/kg (BW) FNT; and FNT20 which received 20 mg/kg (BW) FNT. The corn oil and FNT were fed orally for 28 consecutive days. At the end of the study, the blood was taken, and the kidney was obtained for biochemistry evaluation and histological observation. Results: The AChE activity was significantly inhibited in the FNT20 group (p≤0.05) compared to the control group and FNT10 and the rats exhibited the signs and symptoms of toxicity such as lacrimation, piloerection, hypoactivity, and tremor. Plasma creatinine and BUN levels showed a significant increase (p≤0.05) in FNT treated groups, but the superoxide dismutase and glutathione level were significantly reduced (p≤0.05). The malondialdehyde and protein carbonyl level were elevated significantly (p≤0.05) in FNT treated groups. Histopathological observation revealed morphological changes, including atrophy of the glomerulus and presence of non-amyloid substances in FNT treated groups. Conclusion: Even at the dose that did not inhibit the AChE activity, FNT was found to reduce the renal function and induce oxidative damage on the kidney of male Sprague Dawley rats.

The protective role of oleuropein against diethylnitrosamine and phenobarbital induced damage in rats

2019 ◽  
Vol 44 (5) ◽  
pp. 714-721
Author(s):  
Nurefşan Özeren ◽  
Mehmet Ali Kisacam ◽  
Gonca Ozan Kocamuftuoglu ◽  
Nalan Kaya ◽  
Sema Temizer Ozan
Keyword(s):  
Liver Damage ◽  
Therapeutic Agent ◽  
Biological Properties ◽  
Protective Role ◽  
Control Group ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Sprague Dawley Rats ◽  
Significant Difference

Abstract Objective Liver cancer is amongst the most lethal cancers worldwide. Diethylnitrosamine (DEN) and phenobarbital (PB) are common agents that form reactive oxygen species (ROS). Oleuropein (OLE) has efficient biological properties and used as a therapeutic agent. In this study, we aimed at investigating OLE against DEN + PB induced liver damage. Methods Adult Sprague-Dawley rats were divided into 5 groups (n = 10): Control, DEN, DEN + PB, DEN + PB + OLE and OLE. DEN, DEN + PB, DEN + PB + OLE groups were administered a single dose of 150 mg/kg DEN. After two weeks, DEN + PB and DEN + PB + OLE groups received 500 ppm of PB. 10 mg/kg/day of OLE was orally administered to DEN + PB + OLE and OLE groups. Biochemical and histopathological changes evaluated after the 8 weeks study. Results DEN and PB application with OLE treatment resulted significant differences, alone or combined. Although there was a significant difference among the groups in terms of liver GSH and MDA levels and CAT activities, there was no significant difference among the groups in SOD activity. In the liver sections of the DEN, DEN + PB and OLE groups, increase in some histopathological findings and TUNEL positive cells were increased compared to the control group. Conclusion OLE can be used as a protector against the effects of carcinogens causing liver damage.

The Possible Role of Sclerostin in the Pathogenesis of Tympanosclerosis

2021 ◽  
pp. 1-9
Author(s):  
Yu Huang ◽  
Xiansong Wang ◽  
Fashuai Wu ◽  
Yuqing Lu ◽  
Gengtian Liang ◽  
...  
Keyword(s):  
Tympanic Membrane ◽  
Middle Ear ◽  
Morphological Changes ◽  
Fibrous Tissue ◽  
Inflammatory Cells ◽  
Interstitial Tissue ◽  
Middle Ear Mucosa ◽  
Tissue Proliferation ◽  
Sclerotic Lesions ◽  
Experimental Group

<b><i>Objective:</i></b> The aim of this study was to investigate sclerostin (SOST) expression in a rat model of experimental tympanosclerosis (TS) and its possible role in the formation of TS. <b><i>Materials and Methods:</i></b> Thirty-four SD rats were randomly divided into 2 groups: experimental group (<i>n</i> = 17) and normal group (<i>n</i> = 17). The left tympanic cavities in the experimental group were inoculated with methicillin-resistant <i>Staphylococcus aureus</i>. The changes of tympanic membranes were examined and recorded under otoendoscope. Haematoxylin-eosin staining was adopted to detect the morphological changes in the tympanic membrane and middle ear mucosa. Immunohistochemistry and Western blot analysis were used to observe the expression of SOST, Wnt3a, β-catenin, and P-ERK1/2. <b><i>Results:</i></b> In the experimental group, sclerotic lesions were observed in 54.5% ears in the end of 6 weeks. Morphological changes such as mucosa incrassation, inflammatory cells infiltration, fibrous tissue proliferation, and interstitial tissue incrassation prominently appeared in the tympanic membrane and middle ear mucosa. SOST protein was mainly distributed in the cytoplasm of epithelial cells and gland cells, the expression of which increased significantly in the calcified experimental ears. In addition, expression levels of Wnt3a, β-catenin, and P-ERK1/2 increased significantly in the calcified group too. <b><i>Conclusion:</i></b> The upregulated expression level of SOST may be involved in the formation of TS, first, through the pro-phosphorylation of ERK1/2 in the inflammatory stage, and then through the enhancement of Wnt3a in the osteogenic stage.

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