scholarly journals Comparison of therapeutic effects between topical 8-oxo-2′-deoxyguanosine and corticosteroid in ocular alkali burn model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Hyun Kim ◽  
Sang-Taek Im ◽  
Jin Young Yoon ◽  
Seunghoon Kim ◽  
Mee Kum Kim ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Inflammatory Cells ◽  
Treated Group ◽  
Prednisolone Acetate ◽  
Therapeutic Effects ◽  
Alkali Burn ◽  
Tnf Α ◽  
Phosphate Buffered Saline

AbstractWe compared the therapeutic effects of topical 8-oxo-2′-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.

scholarly journals Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia

2016 ◽  
Vol 213 (9) ◽  
pp. 1851-1864 ◽  
Author(s):  
Keer Sun ◽  
Vijaya Kumar Yajjala ◽  
Christopher Bauer ◽  
Geoffrey A. Talmon ◽  
Karl J. Fischer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Influenza Infection ◽  
Treatment Strategies ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Inflammatory Cells ◽  
Oxidase Inhibitor ◽  
Lung Damage ◽  
Surrounding Tissue ◽  
Staphylococcus Aureus Pneumonia

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)–deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress–associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.

scholarly journals Low Energy Shock Wave Therapy Inhibits Inflammatory Molecules and Suppresses Prostatic Pain and Hypersensitivity in a Capsaicin Induced Prostatitis Model in Rats

2019 ◽  
Vol 20 (19) ◽  
pp. 4777 ◽  
Author(s):  
Hung-Jen Wang ◽  
Pradeep Tyagi ◽  
Yu-Ming Chen ◽  
Michael B. Chancellor ◽  
Yao-Chi Chuang
Keyword(s):  
Shock Wave ◽  
Inflammatory Cells ◽  
Low Energy ◽  
Therapeutic Effects ◽  
Inflammatory Reactions ◽  
Caspase 1 ◽  
Tnf Α ◽  
Pain Reaction ◽  
Cox 2 ◽  
Inflammatory Molecules

The effect of low energy shock wave (LESW) therapy on the changes of inflammatory molecules and pain reaction was studied in a capsaicin (10 mM, 0.1 cc) induced prostatitis model in rats. Intraprostatic capsaicin injection induced a pain reaction, including closing of the eyes, hypolocomotion, and tactile allodynia, which effects were ameliorated by LESW treatment. LESW therapy (2Hz, energy flux density of 0.12 mJ/mm2) at 200 and 300 shocks significantly decreased capsaicin-induced inflammatory reactions, reflected by a reduction of tissue edema and inflammatory cells, COX-2 and TNF-α stained positive cells, however, the therapeutic effects were not observed at 100 shocks treated group. Capsaicin-induced IL-1β, COX-2, IL-6, caspase-1, and NGF upregulation on day 3 and 7, while NALP1 and TNF-α upregulation was observed on day 7. LESW significantly suppressed the expression of IL-1β, COX-2, caspase-1, NGF on day 3 and IL-1β, TNF-α, COX-2, NALP1, caspase-1, NGF expression on day 7 in a dose-dependent fashion. LESW has no significant effect on IL-6 expression. Intraprostatic capsaicin injection activates inflammatory molecules and induces prostatic pain and hypersensitivity, which effects were suppressed by LESW. These findings might be the potential mechanisms of LESW therapy for nonbacterial prostatitis in humans.

Potent Inhibitory Effects of Quercetin on Inflammatory Responses of Collagen-Induced Arthritis in Mice

2019 ◽  
Vol 19 (3) ◽  
pp. 308-315 ◽  
Author(s):  
Kiichiro Kawaguchi ◽  
Masahiro Kaneko ◽  
Ryo Miyake ◽  
Hiroaki Takimoto ◽  
Yoshio Kumazawa
Keyword(s):  
Oral Administration ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Knee Joints ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Flavonoid Quercetin

Background: Production of tumor necrosis factor (TNF)-α by inflammatory cells in lesions is the hallmark of the pathogenesis of rheumatoid arthritis (RA). Regulation of inflammatory responses in knee joints of patients with RA is critical for improving severe symptoms. Flavonoids have inhibitory effects on the acute and chronic inflammatory responses caused by TNF-α. The flavonoid quercetin (QUER) is one of the most prominent dietary antioxidants. Objective: The present study investigated the preventive and therapeutic effects of QUER on inflammatory responses in collagen-induced arthritis (CIA) in mice. Methods: Mice with CIA, a mouse model for RA, were treated with QUER orally three times a week either from the second immunization with collagen (day 21) or day 28 when symptoms of CIA had developed midway. Results: In both cases, inflammation-related clinical scores of knee joints were significantly reduced by treatment with QUER. Histological analyses showed that the representative characteristics of RA, such as damage to interchondral joints, infiltration of inflammatory cells, and pannus formation, were significantly reduced by QUER treatment. Oral administration of QUER significantly decreases lipopolysaccharide (LPS)-induced TNF-α production in a dose-dependent manner. Expression of TNF- α mRNA in knee joints was decreased in QUER-treated mice, compared with those of CIA controls. Conclusion: These results suggest that oral administration of QUER might effectively improve symptoms of RA.

scholarly journals T Cell Vaccination Inhibits Th1/Th17/Tfh Frequencies and Production of Autoantibodies in Collagen-Induced Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Shan Li ◽  
Xiaoyin Niu ◽  
Yebin Xi ◽  
Shaohua Deng ◽  
Chengzhen Li ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Onset ◽  
Inflammatory Cells ◽  
Type Ii Collagen ◽  
Treated Group ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Cell Responses ◽  
T Cell Vaccination

The aim of this study is to determine whether the regulatory role of T cell vaccination (TCV) is through inhibition of Th1/Th17/Tfh and production of autoantibodies on collagen-induced arthritis (CIA). First, CIA mice were treated with TCV. After disease onset, the incidence and severity of change in joint histopathology were evaluated. Mice in the TCV-treated group showed less disease severity and less infiltration of inflammatory cells in the joint sections. TCV decreased the frequencies of Th1/Th17/Tfh cells and related cytokines. Reduction of IL-21 may be associated with both Tfh and Th17, which further influence B cell and T cell responses. In addition, inhibition of Th1/Th17/Tfh frequencies led to the reduced expression of T-bet, RORα, RORγt, and Bcl6. Lastly, the proliferation of type-II-collagen-(CII-) specific T cells and the production of anti-CII antibodies were inhibited in the TCV-treated group. The results provide novel evidence that the therapeutic effects of TCV on CIA are associated with the inhibition of Th1/Th17/Tfh frequencies and autoantibodies production.

scholarly journals Effects of inhalation and intravenous administration of allogeneic mesenchymal bone marrow stromal cells in a bleomycin-induced model of pulmonary fibrosis in rabbits

2018 ◽  
Vol 19 (4) ◽  
pp. 88-96
Author(s):  
A. V. Averyanov ◽  
A. G. Konoplyannikov ◽  
F. G. Zabozlaev ◽  
O. V. Danilevskaya ◽  
M. A. Konoplyannikov ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Stromal Cells ◽  
Treated Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Treatment Groups ◽  
Tnf Α ◽  
The Standard Model ◽  
Marrow Mesenchymal Stem Cells ◽  
Tgf Β1

Aim:to perform a comparative analysis of the effi cacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fi brosis.Materials and methods.After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × 106 allogeneic BMMSCs, other 5 rabbits – 2 × 107 MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each.Results.Both groups treated with BMMSCs had a signifi cantly lower Ashcroft fi brosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Levels of TNF-α and TGF-β1 in BAL fl uids tended to decrease in treatment groups, but did not differ signifi cantly from control. A similar picture was observed in the cytological analysis of BAL.Conclusion.In general, both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fi brosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies. 

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.

Activation and priming of neutrophil nicotinamide adenine dinucleotide phosphate oxidase and phospholipase A2 are dissociated by inhibitors of the kinases p42ERK2and p38SAPK and by methyl arachidonyl fluorophosphonate, the dual inhibitor of cytosolic and calcium-independent phospholipase A2

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2469-2477 ◽  
Author(s):  
Elahe Mollapour ◽  
David C. Linch ◽  
Pamela J. Roberts
Keyword(s):  
Nadph Oxidase ◽  
Phospholipase A2 ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Superoxide Production ◽  
Dual Inhibitor ◽  
Nadph Oxidase Activity ◽  
Gm Csf ◽  
Tnf Α ◽  
Arachidonate Release

Abstract Arachidonic acid (AA) generated by phospholipase A2(PLA2) is thought to be an essential cofactor for phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Both enzymes are simultaneously primed by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor–α (TNF-α). The possibility that either unprimed or cytokine-primed responses of PLA2 or NADPH oxidase to the chemotactic agents formyl-methionyl-leucyl-phenylalanine (FMLP) and complement factor 5a (C5a) could be differentially inhibited by inhibitors of the mitogen-activated protein (MAP) kinase family members p42ERK2 (PD98059) and p38SAPK(SB203580) was investigated. PD98059 inhibited the activation of p42ERK2 by GM-CSF, TNF-α, and FMLP, but it did not inhibit FMLP-stimulated superoxide production in either unprimed or primed neutrophils. There was no significant arachidonate release from unprimed neutrophils stimulated by FMLP, and arachidonate release stimulated by calcium ionophore A23187 was not inhibited by PD98059. In contrast, PD98059 inhibited both TNF-α– and GM-CSF–primed PLA2 responses stimulated by FMLP. On the other hand, SB203580 inhibited FMLP-superoxide responses in unprimed as well as TNF-α– and GM-CSF–primed neutrophils, but failed to inhibit TNF-α– and GM-CSF–primed PLA2 responses stimulated by FMLP, and additionally enhanced A23187-stimulated arachidonate release, showing that priming and activation of PLA2 and NADPH oxidase are differentially dependent on both the p38SAPK and p42ERK2 pathways. Studies using C5a as an agonist gave similar results and confirmed the findings with FMLP. In addition, methyl arachidonyl fluorophosphonate (MAFP), the dual inhibitor of c and iPLA2 enzymes, failed to inhibit superoxide production in primed cells at concentrations that inhibited arachidonate release. These data demonstrate that NADPH oxidase activity can be dissociated from AA generation and indicate a more complex role for arachidonate in neutrophil superoxide production.

scholarly journals The Anti-Inflammatory Effects of Fermented Herbal Roots of Asparagus cochinchinensis in an Ovalbumin-Induced Asthma Model

2018 ◽  
Vol 7 (10) ◽  
pp. 377 ◽  
Author(s):  
Jun Choi ◽  
Ji Kim ◽  
Jin Park ◽  
Mi Lee ◽  
Bo Song ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Airway Remodeling ◽  
Inflammatory Cells ◽  
Treated Group ◽  
Therapeutic Effects ◽  
Molecular Response ◽  
Asthma Model ◽  
Cholinergic Regulation ◽  
Asparagus Cochinchinensis ◽  
Pharmacologically Active

Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.

scholarly journals The Curative Effect of Zingiber Officinale and Cinnamomum Zeylanicum Extracts on Experimental Trichinella Spiralis Infection

2021 ◽  
Author(s):  
Marwa Ahmed Mohamed Salama ◽  
Nahed Elsayed Mostafa ◽  
Naglaa Fathy Abd El-Aal ◽  
Howayda S. F. Moawad ◽  
Samar Kamel Hammad ◽  
...  
Keyword(s):  
Trichinella Spiralis ◽  
Zingiber Officinale ◽  
Treated Group ◽  
Health Concern ◽  
Therapeutic Effects ◽  
Cinnamomum Zeylanicum ◽  
Infected Control ◽  
Transmission Electron ◽  
Tnf Α ◽  
Α Level

Abstract Trichinellosis is a re-emerging zoonotic disease that has become a public health concern since its reported human outbreaks in many countries. The traditional therapy has many adverse effects in addition to the developing resistance. So, this necessitates finding effective natural alternatives. The current study targeted to assess the potential therapeutic effects of Zingiber officinale and Cinnamomum zeylanicum in comparison to albendazole, a conventional therapy for treatment of trichinosis. Sixty mice were classified into five groups (12 mice each), non-infected control, infected control, combined albendazole and prednisolone, Zingiber officinale, and Cinnamomum zeylanicum treated groups. Mice sacrifice was performed on the 7th and 35th days post infection for intestinal and muscular phases respectively. Efficiency of the used preparations was assessed by parasitological, histopathological, immunohistochemical, biochemical studies in addition to ultrastructural evaluation using transmission electron microscopy. A significant reduction in the mean number of T. spiralis adults and larvae was observed in Zingiber officinale and Cinnamomum zeylanicum treated groups, (64.5%, 50.8%) and (68%, 54.6%) respectively. Also, both extracts showed moderate cytoplasmic reactivity for TGF-β1, (69.3% & 67.8%) respectively. The highest reduction in serum TNF- α level was observed in Zingiber officinale treated group during the muscle phase (58.4%) while in the intestinal phase was 50%. The ultrastructural study revealed degenerative effects on both adults and larvae in addition to obvious improvement of the histopathological changes in the small intestine and muscles. We concluded that these herbal extracts especially Zingiber officinale can be considered a practical and successful alternative for the treatment of trichinellosis.

scholarly journals Hu-Lu-Ba-Wan Attenuates Diabetic Nephropathy in Type 2 Diabetic Rats through PKC-α/NADPH Oxidase Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lishan Zhou ◽  
Hui Dong ◽  
Yi Huang ◽  
Lijun Xu ◽  
Xin Zou ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nadph Oxidase ◽  
Signaling Pathway ◽  
Superoxide Anion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Control Group ◽  
Type 2 Diabetic

Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-α) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-αin renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.

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