scholarly journals NADPH Oxidase Inhibitor Apocynin Attenuates PCB153-Induced Thyroid Injury in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ablikim Abliz ◽  
Chen Chen ◽  
Wenhong Deng ◽  
Weixing Wang ◽  
Rongze Sun
Keyword(s):  
Thyroid Hormone ◽  
Nadph Oxidase ◽  
Inflammatory Cytokines ◽  
Thyroid Dysfunction ◽  
Thyroid Tissue ◽  
Oxidase Inhibitor ◽  
Control Group ◽  
Ros Generation ◽  
Sprague Dawley ◽  
Serum Thyroid Hormone

PCBs, widespread endocrine disruptors, cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. However, the exact mechanism of thyroid dysfunction caused by PCBs is still unknown. In order to clarify the hypotheses that NADPH oxidase (NOX) and subsequent NF-κB pathway may play roles in thyroid dysfunction, sixty Sprague-Dawley rats were randomly divided into four groups: control group, PCB153 treated (PCB) group, received apocynin with PCB153 treatment (APO + PCB) group, and drug control (APO) group. Serum thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. NOX2, 8-OHdG, and NF-κB expression in the thyroid tissue was evaluated by immune-histochemical staining. Oxidative stress and inflammatory cytokines were detected. The following results were reduced after apocynin treatment: (1) serum thyroid hormone, (2) thyroid pathological injuries, (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum inflammatory cytokines, and (6) thyroid expression of NOX2, 8-OHdG, and NF-κB. These results suggested that NOX inhibition attenuates thyroid dysfunction induced by PCB in rats, presumably because of its role in preventing ROS generation and inhibiting the activation of NF-κB pathway. Our findings may provide new therapeutic targets for PCBs induced thyroid dysfunction.

Abstract 107: Apocynin Attenuates Isoproterenol-induced Myocardial Injury: Implications For Targeting Nadph Oxidase In Myocardial Fibrogenesis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Yu Chen ◽  
Jingang Cui ◽  
Qinbo Yang ◽  
Chenglin Jia ◽  
Minqi Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Myocardial Fibrosis ◽  
Myocardial Injury ◽  
Oxidase Inhibitor ◽  
Ros Generation ◽  
Dependent Manner ◽  
Expression Of Genes ◽  
Therapeutic Development ◽  
Myocardial Injuries

Myocardial fibrosis results from cardiac injuries caused by various pathophysiological mechanisms including myocardial infarction, leading to destruction of myocardial architecture and progressive cardiac dysfunction. Oxidative stress is likely involved in myocardial ischemic injury and the subsequent tissue remodeling mediated by myocardial fibrogenesis. Our current study aimed to evaluate the implication of NADPH oxidase in overproduction of reactive oxygen species and its contribution to the pathogenesis of myocardial fibrogenesis after ischemic injuries. The effects of Apocynin, a selective NADPH oxidase inhibitor, were evaluated in the mouse model of isoproterenol-induced myocardial injury by histopathological approaches and whole-genome gene expression profiling. The results demonstrated that Apocynin was able to inhibit the development of ISO-induced myocardial necrotic lesions and fibrogenesis in a dose-dependent manner. Moreover, the preventive effects of Apocynin on myocardial injuries were associated with suppressed expression of genes implicated in inflammation responses and extracellular matrix, which were remarkably upregulated by isoproterenol administration. In summary, o ur study provides proof-of-concept for the involvement of NADPH oxidase-mediated ROS generation in myocardial ischemic injuries and fibrogenesis, which will benefit the mechanism-based therapeutic development targeting NADPH oxidase and oxidative stress in treating myocardial fibrosis and related disorders.

Diabetes induces pulmonary artery endothelial dysfunction by NADPH oxidase induction

2008 ◽  
Vol 295 (5) ◽  
pp. L727-L732 ◽  
Author(s):  
Jose G. Lopez-Lopez ◽  
Javier Moral-Sanz ◽  
Giovanna Frazziano ◽  
Maria J. Gomez-Villalobos ◽  
Jorge Flores-Hernandez ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Pulmonary Arteries ◽  
Diabetic Rats ◽  
Oxidase Inhibitor ◽  
No Synthase ◽  
Superoxide Production ◽  
Regulatory Subunit ◽  
Sprague Dawley ◽  
Relaxant Response

Recent data suggest that diabetes is a risk factor for pulmonary hypertension. The aim of the present study was to analyze whether diabetes induces endothelial dysfunction in pulmonary arteries and the mechanisms involved. Male Sprague-Dawley rats were randomly divided into a control (saline) and a diabetic group (70 mg/kg−1 streptozotocin). After 6 wk, intrapulmonary arteries were mounted for isometric tension recording, and endothelial function was tested by the relaxant response to acetylcholine. Protein expression and localization were measured by Western blot and immunohistochemistry and superoxide production by dihydroethidium staining. Pulmonary arteries from diabetic rats showed impaired relaxant response to acetylcholine and reduced vasoconstrictor response to the nitric oxide (NO) synthase inhibitor l-NAME, whereas the response to nitroprusside and the expression of endothelial NO synthase remained unchanged. Endothelial dysfunction was reversed by addition of superoxide dismutase or the NADPH oxidase inhibitor apocynin. An increase in superoxide production and increased expression of the NADPH oxidase regulatory subunit p47phox were also found in pulmonary arteries from diabetic rats. In conclusion, the pulmonary circulation is a target for diabetes-induced endothelial dysfunction via enhanced NADPH oxidase-derived superoxide production.

Microstructural changes and immunohistological analysis of pro-inflammatory cytokines in spleens of lipopolysaccharide-induced rats

2018 ◽  
Author(s):  
Y. B. Zhong ◽  
X. L. Zhang ◽  
M. Y. Lv ◽  
X. F. Hu ◽  
Y. Li
Keyword(s):  
Inflammatory Cytokines ◽  
Optical Density ◽  
Normal Saline ◽  
Interleukin 1 ◽  
Saline Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Lymphoid Follicles ◽  
Pro Inflammatory Cytokines

This study investigated splenic status changes in weaned Sprague-Dawley rats induced by lipopolysaccharide. There were forty 26-day-old rats selected randomly and equally divided into two groups. The treatment group received daily single doses of lipopolysaccharide, and the control group was treated with normal saline. We conducted haematoxylin-eosin staining, immunohistochemical staining and semi-quantitative optical density analysis for both groups on the 29th, 32nd, 35th and 38th days after treatment. The results indicated that splenic marginal zone in the lipopolysaccharide group was thinner or disappeared compared to that of the saline group. However, the periarterial lymphoid sheath and the diameters of splenic lymphoid follicles appeared thicker and wider than those in the saline group (P less than 0.05). The expression of interleukin-1 beta, interleukin-6 and tumour necrosis factor alpha was mainly localized within the periarterial lymphoid sheath and splenic lymphoid follicles in the lipopolysaccharide treated rats. The integrated optical density and the average optical density in the lipopolysaccharide group were greater than those in the normal saline treated group (P less than 0.05). In conclusion, splenic immune function is probably strengthened by altering microstructures and releasing pro-inflammatory cytokines following lipopolysaccharide treatment.

scholarly journals Does thyroid dysfunction influence inflammatory mediators in experimental periodontitis?

2021 ◽  
Vol 55 (3) ◽  
pp. 131-141
Author(s):  
Vitaliy Shcherba ◽  
Inna Krynytska ◽  
Mariya Marushchak ◽  
Mykhaylo Korda
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Thyroid Dysfunction ◽  
Solid Phase ◽  
White Male ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Group Iii ◽  
Group I ◽  
Tnf Α

Abstract Objective. The aim of the present study was to investigate the presence of inflammatory mediators in rats with only periodontitis and periodontitis in a setting of hyper- and hypo-thyroidism and to analyze the correlative linkages between inflammatory mediators and thyroid hormones. Methods. White male 12–14 weeks old inbred rats (n=48) weighing 180–200 g were employed in the experiment. They were randomly divided into the following groups: Group I – control group, Group II – group with a model of periodontitis, Group III – group with a periodontitis in a setting of hyperthyroidism, and Group IV – group with periodontitis in a setting of hypothyroidism. The presence of tumor-necrosis factor-α (TNF-α) and interleukins IL-1β and IL-10 in the periodontal homogenate supernatant was studied by a solid-phase enzyme-linked immunosorbent assay. Results. It was shown that experimental lipopolysaccharide (LPS)-induced periodontitis is accompanied by hyperproduction of pro-inflammatory cytokines (TNF-α, IL-1β) and reduction of anti-inflammatory cytokines (IL-10), whereas TNF-α underwent to maximum changes. Thyroid dysfunction exacerbates cytokine imbalance and severity of inflammation in experimental LPS-induced periodontitis, especially pronounced at hyperthyroidism, as evidenced by the predominance of TNF-α and IL-1β levels in the periodontal homogenate supernatant by 38.5% (р<0.01) and 75.6% (p<0.001), respectively, hyperthyroid over the euthyroid, and by 20.1% (p<0.05) and 24.1% (p<0.05), respectively, over the hypothyroid rats. Conclusions. Thyroid dysfunction, especially hyperthyroidism, may play an important role in the pro-inflammatory response in periodontitis. Hyperproduction of inflammatory mediators in thyroid dysfunction can induce a noticeable damage in the whole apparatus of the periodontium, thereby causing progression of periodontitis.

scholarly journals Establishment of cervical dynamic and static imbalance models and preliminary study on the mechanism of cervical degeneration in rats

2019 ◽  
Vol 26 (2) ◽  
pp. 107-116
Author(s):  
Haibo Li ◽  
Jianjian Yin ◽  
Yongjing Huang ◽  
Nanwei Xu ◽  
Liang Chen ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Test Group ◽  
Cervical Disc ◽  
Control Group ◽  
Sprague Dawley ◽  
Intervertebral Disc Space ◽  
Disc Space ◽  
X Ray ◽  
Post Operation

This study aimed to observe dynamically the changes of x-ray, histomorphology appearance and serum inflammatory cytokines of cervical degenerative disease in rat models and to discuss the mechanism of cervical degeneration. Sixty Sprague Dawley rats were randomised into test ( n = 45) and control ( n = 15) groups, which were randomly subdivided into three groups corresponding to 1, 3 and 6 mo post operation. At the corresponding postoperative stage, cervical x-ray films were acquired, and intervertebral disc space and intervertebral foramen size were measured. Some serum inflammatory cytokines from all rats were quantitatively determined. Then, the morphological change in cervical intervertebral disc specimens stained with hematoxylin and eosin was observed. The results were analysed and compared among groups. Compared to the control group, the cervical x-ray and histomorphology appearance of rats in the test group showed varying degrees of degeneration. Furthermore, the serum IL-1β, TNF-α and IL-10 in the test group increased significantly at the corresponding postoperative stage ( P < 0.05, P < 0.01 and P < 0.001, respectively) compared to the control group. This model of cervical disc degeneration can accelerate imaging and histological degeneration, but it may be accompanied by changes in serum inflammatory cytokines levels.

scholarly journals Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients

2015 ◽  
Vol 173 (3) ◽  
pp. 333-340 ◽  
Author(s):  
Mitsuru Ito ◽  
Akira Miyauchi ◽  
Shino Kang ◽  
Mako Hisakado ◽  
Waka Yoshioka ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Tissue ◽  
Serum Levels ◽  
Substantial Effect ◽  
Papillary Thyroid ◽  
Remnant Thyroid ◽  
Hormone Balance ◽  
Postoperative Serum ◽  
Serum Thyroid Hormone ◽  
Serum Tsh

ObjectiveWe and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T3) levels during levothyroxine (l-T4) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established.MethodsWe retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TT+supplementall-T4(+l-T4) group (n=103); the HT+l-T4group (n=56); and the HT-alone group (n=94). We compared the postoperative serum levels of free T4(FT4) and free T3(FT3) and the FT3/FT4ratio in individual patients with those of controls matched by serum TSH levels.ResultsThe TT+l-T4group had significantly higher FT4(P<0.001), lower FT3(P<0.01) and lower FT3/FT4(P<0.001) levels compared to the controls. The HT+l-T4group had FT4, FT3and FT3/FT4levels equivalent to those of the controls. The HT-alone group had significantly lower FT4(P<0.01), equivalent FT3(P=0.083), and significantly higher FT3/FT4(P<0.001) ratios than the controls.ConclusionsThe presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T3production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T3levels.

Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression

2006 ◽  
Vol 290 (2) ◽  
pp. F345-F356 ◽  
Author(s):  
L. Xia ◽  
H. Wang ◽  
H. J. Goldberg ◽  
S. Munk ◽  
I. G. Fantus ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
High Glucose ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Fold Increase ◽  
Collagen Iv ◽  
Oxidase Inhibitor ◽  
Ros Generation ◽  
Rt Pcr ◽  
Diabetic Glomerulosclerosis

Excess collagen IV expression by mesangial cells contributes to diabetic glomerulosclerosis. We hypothesized that in high glucose reactive oxygen species (ROS) generation by NADPH oxidase is PKC dependent and required for collagen IV expression by mesangial cells. In rat mesangial cells cultured in 5 mM (NG) or 25 mM d-glucose (HG), RT-PCR and Western immunoblotting detected p22phox and p47phox mRNA and protein, respectively. Quantitative real-time RT-PCR analyzed collagen IV mRNA. With the use of confocal microscopy, ROS were detected with dichlorofluorescein and intracellular collagen IV by immunofluorescence. In HG, ROS were generated within 1 h, sustained up to 48 h, and prevented by a NADPH oxidase inhibitor, diphenylenechloride iodonium (DPI), or a conventional PKC isozyme inhibitor, Gö6976. In NG, phorbol myristate acetate stimulated ROS generation that was inhibited with DPI. In HG, expression of p22phox and p47phox was increased within 3 to 6 h and inhibited by Gö6976. In HG, Gö6976 or transfection with antisense against p22phox reversed the 1.8-fold increase in collagen IV mRNA. In HG, the antioxidants Tempol or Tiron, or transfection with antisense against p22phox or p47phox, prevented ROS generation and the 2.3-fold increase in collagen IV protein. Increased mitochondrial redox potential in HG was unaffected by transfection with antisense against p22phox. We conclude that in HG, mesangial cell ROS generation by upregulated NADPH oxidase is dependent on conventional PKC isozymes and also required for collagen IV expression.

Low shear stress preferentially enhances IKK activity through selective sources of ROS for persistent activation of NF-κB in endothelial cells

2007 ◽  
Vol 292 (1) ◽  
pp. C362-C371 ◽  
Author(s):  
Sumathy Mohan ◽  
Koichi Koyoma ◽  
Amalraj Thangasamy ◽  
Hiroyasu Nakano ◽  
Randolph D. Glickman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Nadph Oxidase ◽  
Significant Proportion ◽  
Time Frame ◽  
Oxidase Inhibitor ◽  
Ros Generation ◽  
High Shear ◽  
Low Shear Stress ◽  
Low Shear

NF-κB signaling pathway has been known to play a major role in the pathological process of atherogenesis. Unlike high shear stress, in which the NF-κB activity is transient, our earlier studies have demonstrated a persistent activation of NF-κB in response to low shear stress in human aortic endothelial cells. These findings partially explained why low shear regions that exist at bifurcations of arteries are prone to atherosclerosis, unlike the relatively atheroprotective high shear regions. In the present study, we further investigated 1) the role of NF-κB signaling kinases (IKKα and β) that may be responsible for the sustained activation of NF-κB in low shear stress and 2) the regulation of these kinases by reactive oxygen species (ROS). Our results demonstrate that not only is a significant proportion of low shear-induced-kinase activity is contributed by IKKβ, but it is also persistently induced for a prolonged time frame. The IKK activity (both α and β) is blocked by apocynin (400 μM), a specific NADPH oxidase inhibitor, and diphenyleneiodonium chloride (DPI; 10 μM), an inhibitor of flavin-containing oxidases like NADPH oxidases. Determination of ROS also demonstrated an increased generation in low shear stress that could be blocked by DPI. These results suggest that the source of ROS generation in endothelial cells in response to low shear stress is NADPH oxidase. The DPI-inhibitable component of ROS is the primary regulator of specific upstream kinases that determine the persistent NF-κB activation selectively in low shear-induced endothelial cells.

The effect of thyroid dysfunction on nesfatin-1 and adiponectin levels in rats

2017 ◽  
Vol 32 (3) ◽  
Author(s):  
Emine Atıci ◽  
Rasim Mogulkoc ◽  
Abdulkerim Kasım Baltaci ◽  
Esma Menevse
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Thyroid Dysfunction ◽  
The Other ◽  
High Dose ◽  
Fat Cells ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Experimental Thyroid

AbstractBackgroundChanges in thyroid hormone concentrations may affect adiponectin concentrations through various mechanisms. A molecule released primarily from the fat cells adiposities; adiponectin has important effects on the regulation of body weight.AimThe present study aimed to explore the effects of experimental thyroid dysfunction and its treatment on nesfatin-1 and adiponectin levels in rats.MethodsThe study included 40 adult male Sprague-Dawley rats which were grouped as follows: (1) control; (2) hypothyroidism [hypothyroidism was induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 3 weeks]; (3) hypothyroidism + thyroxine group [after hypothyroidism was induced by 2-week PTU injection, they were treated with high-dose L-thyroxine (1.5 mg/kg/day) for 1 week]; (4) hyperthyroidism [hyperthyroidism was induced by 3-weeks’ thyroxine injection (0.3 mg/kg/day)]; (5) hyperthyroidism + PTU (after hyperthyroidism was induced by 2-weeks’ thyroxine injection, the animals were given 10 mg/kg/day PTU for 1 week). Blood samples taken at the end of the study were analyzed to measure nesfatin-1 and adiponectin levels.ResultsIt was found that nesfatin-1 levels increased in hypothyroidism, while adiponectin levels decreased (p < 0.001). In experimental hyperthyroidism, on the other hand, both nesfatin-1 and adiponectin levels were found significantly elevated (p < 0.001).ConclusionThe results of the study indicate that nesfatin-1 and adiponectin levels were modified considerably in hypo- and hyperthyroidism, whereas with the restoration of the thyroid function, modified hormone levels went back to normal.

scholarly journals Apocynin Attenuates Cerebral Infarction after Transient Focal Ischaemia in Rats

2007 ◽  
Vol 35 (4) ◽  
pp. 517-522 ◽  
Author(s):  
LL Tang ◽  
K Ye ◽  
XF Yang ◽  
JS Zheng
Keyword(s):  
Nadph Oxidase ◽  
Cerebral Infarction ◽  
Infarct Size ◽  
Oxidase Activity ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Treated Group ◽  
Oxidase Inhibitor ◽  
Sprague Dawley ◽  
Nadph Oxidase Activity ◽  
Focal Ischaemia

This study investigated whether inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase attenuates cerebral infarction after transient focal ischaemia in rats. Focal ischaemia (1.5 h) was produced in male Sprague-Dawley rats (250 − 280 g) by middle cerebral artery occlusion. Some rats also received treatment with 50 mg/kg apocynin, a NADPH oxidase inhibitor, by intraperitoneal injection 30 min prior to reperfusion. Two hours after reperfusion, brains were harvested to measure NADPH oxidase activity and superoxide levels. After 24 h, the remaining brains were harvested to investigate infarct size. NADPH oxidase activity and superoxide level were all augmented 2 h after reperfusion compared with controls. Apocynin treatment significantly reduced NADPH oxidase activity and superoxide levels. Cerebral infarct size was significantly smaller in the apocynin-treated group compared with those undergoing ischaemia/reperfusion alone. These results indicate that inhibition of NADPH oxidase attenuates cerebral infarction after transient focal ischaemia in rats, suggesting that inhibition of NADPH oxidase may provide a therapeutic strategy for ischaemic stroke.

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