scholarly journals Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

1997 ◽  
Vol 41 (2) ◽  
pp. 308-313 ◽  
Author(s):  
T Matsumoto ◽  
K Tateda ◽  
S Miyazaki ◽  
N Furuya ◽  
A Ohno ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Survival Rate ◽  
Protective Effect ◽  
Specific Activity ◽  
Bacterial Colonization ◽  
Interleukin 1 ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Bacterial Clearance ◽  
Necrosis Factor Alpha

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

scholarly journals Anti-Amnesic Effect of Walnut via the Regulation of BBB Function and Neuro-Inflammation in Aβ1-42-Induced Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 976
Author(s):  
Jong Min Kim ◽  
Uk Lee ◽  
Jin Yong Kang ◽  
Seon Kyeong Park ◽  
Eun Jin Shin ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Protective Effect ◽  
Tumor Necrosis ◽  
Juglans Regia ◽  
Interleukin 1 ◽  
Tumor Necrosis Factor Receptor ◽  
Heme Oxygenase 1 ◽  
Necrosis Factor Alpha ◽  
Amnesic Effect ◽  
Necrosis Factor

This study was conducted to assess the protective effect of walnut (Juglans regia L.) extract on amyloid beta (Aβ)1-42-induced institute of cancer research (ICR) mice. By conducting a Y-maze, passive avoidance, and Morris water maze tests with amyloidogenic mice, it was found that walnut extract ameliorated behavioral dysfunction and memory deficit. The walnut extract showed a protective effect on the antioxidant system and cholinergic system by regulating malondialdehyde (MDA) levels, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, acetylcholine (ACh) levels, acetylcholinesterase (AChE) activity, and protein expression of AChE and choline acetyltransferase (ChAT). Furthermore, the walnut extract suppressed Aβ-induced abnormality of mitochondrial function by ameliorating reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP contents. Finally, the walnut extract regulated the expression of zonula occludens-1 (ZO-1) and occludin concerned with blood–brain barrier (BBB) function, expression of tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκB), cyclooxygenase-2 (COX-2), and interleukin 1 beta (IL-1β), related to neuroinflammation and the expression of phosphorylated protein kinase B (p-Akt), caspase-3, hyperphosphorylation of tau (p-tau), and heme oxygenase-1 (HO-1), associated with the Aβ-related Akt pathway.

scholarly journals Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Marwa M. M. Refaie ◽  
Entesar F. Amin ◽  
Nashwa F. El-Tahawy ◽  
Aly M. Abdelrahman
Keyword(s):  
Protective Effect ◽  
Low Dose ◽  
Caspase 3 ◽  
Interleukin 1 ◽  
Treated Group ◽  
Limiting Factors ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.

scholarly journals Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Manal El-khadragy ◽  
Wafa A. Al-Megrin ◽  
Norah A. AlSadhan ◽  
Dina M. Metwally ◽  
Rehab E. El-Hennamy ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Lead Acetate ◽  
Interleukin 1 ◽  
Tween 80 ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Coq10 Supplementation ◽  
Induced Apoptosis ◽  
Testicular Injury

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n=7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v:v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

scholarly journals Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Arduino A. Mangoni ◽  
Angelo Zinellu ◽  
Salvatore Sotgia ◽  
Ciriaco Carru ◽  
Matteo Piga ◽  
...  
Keyword(s):  
Rheumatic Disease ◽  
Vascular Inflammation ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Disease States ◽  
Autoimmune Rheumatic Disease ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Meta Analyses

There is good epidemiological evidence that patients with autoimmune rheumatic disease states, particularly rheumatoid arthritis, have an increased risk of cardiovascular morbidity and mortality when compared to the general population. The presence of a chronic systemic proinflammatory state in this patient group disrupts the structural and functional integrity of the endothelium and the arterial wall, favouring the onset and progression of atherosclerosis. A significant role in the detrimental effects of inflammation on endothelial function and vascular homeostasis is played by specific proatherosclerotic cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Recent systematic reviews and meta-analyses have shown that treatment with methotrexate, a first-line disease-modifying antirheumatic drug (DMARD), is associated with a significant reduction in atherosclerosis-mediated cardiovascular events, such as myocardial infarction and stroke, and mortality, when compared to other DMARDs. This suggests that methotrexate might exert specific protective effects against vascular inflammation and atherosclerosis in the context of autoimmune rheumatic disease. This review discusses the available evidence regarding the potential antiatherosclerotic effects of methotrexate through the inhibition of TNF-α, IL-1, and IL-6 and provides suggestions for future experimental and human studies addressing this issue.

Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer

2020 ◽  
Vol 39 (5) ◽  
pp. 721-733 ◽  
Author(s):  
D-B Jeon ◽  
H-G Shin ◽  
B-W Lee ◽  
S-H Jeong ◽  
J-H Kim ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Enterococcus Faecalis ◽  
Interleukin 1 ◽  
Mucosal Injury ◽  
Underlying Mechanism ◽  
Gastric Injury ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein ◽  
Consequent Reduction

Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

scholarly journals Human Tear Fluid Protects against Pseudomonas aeruginosa Keratitis in a Murine Experimental Model

2007 ◽  
Vol 75 (5) ◽  
pp. 2325-2332 ◽  
Author(s):  
Mary S. F. Kwong ◽  
David J. Evans ◽  
Minjian Ni ◽  
Brigitte A. Cowell ◽  
Suzanne M. J. Fleiszig
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Bacterial Colonization ◽  
Healing Process ◽  
Tear Fluid ◽  
Protective Mechanism ◽  
Healthy Human ◽  
Epithelial Barrier Function

ABSTRACT Pseudomonas aeruginosa keratitis is an acute sight-threatening infection. We previously reported that human tear fluid could protect individual human corneal epithelial cells in vitro against invasion by and cytotoxicity due to clinical and laboratory isolates of P. aeruginosa and that the protective mechanism was independent of bacteriostatic activity. In the present study, we examined the effects of human tear fluid in vivo. Tears were collected from healthy human volunteers and were studied in vivo in mice. The effects on the virulence of both invasive and cytotoxic clinical isolates of P. aeruginosa were examined. Tear fluid was found to reduce the severity of disease when corneas were challenged with cytotoxic bacteria immediately after scratch injury, and it completely protected against susceptibility to infection by a cytotoxic strain in a model in which corneas were infected during the healing process 6 h after scratching. Visible protection correlated with the inhibition of bacterial colonization 1, 4, and 48 h postinoculation. Tear fluid also significantly reduced the severity of infections caused by invasive P. aeruginosa in the 6-h-healing model. This result also coincided with significantly reduced bacterial colonization at 48 h. In vitro, human tear fluid significantly reduced the ability of invasive and cytotoxic bacteria to translocate across corneal epithelia and increased transepithelial resistance with or without bacterial inoculation. These data show that human tear fluid can protect against P. aeruginosa corneal infection in vivo and that the mechanism likely involves enhanced epithelial barrier function in addition to protection of individual epithelial cells against bacterial internalization and cytotoxicity.

Amelioration of Cisplatin Toxicity in Rat Renal Cortical Slices by Dithiothreitol In vitro

1994 ◽  
Vol 13 (2) ◽  
pp. 89-93 ◽  
Author(s):  
J.G. Zhang ◽  
L.F. Zhong ◽  
M. Zhang ◽  
X.L. Ma ◽  
Y.X. Xia ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Protective Effect ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Metal Chelator ◽  
Rat Renal Cortical Slices ◽  
Antioxidative Action ◽  
Cortical Slices ◽  
Related Increase

1 The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices. 2 The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondiadehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased. 3 Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol I-1 ) ameliorated all these toxic effects of cisplatin in a concentration related manner. 4 The results suggest that the protective mechanism of DTT is its antioxidative action, DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.

scholarly journals Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats Revealed by Anti-Inflammatory Assessments and NMR-Based Metabonomics

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Han ◽  
Huizhu Huang ◽  
Zhong Li ◽  
Mengjuan Gong ◽  
Wan Shi ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Gouty Arthritis ◽  
Pathological Process ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Monosodium Urate ◽  
Necrosis Factor Alpha ◽  
Gut Microbe ◽  
Urate Crystal ◽  
Factor Alpha

The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats.

scholarly journals Innate Lung Defenses and Compromised Pseudomonas aeruginosa Clearance in the Malnourished Mouse Model of Respiratory Infections in Cystic Fibrosis

2000 ◽  
Vol 68 (4) ◽  
pp. 2142-2147 ◽  
Author(s):  
H. Yu ◽  
S. Z. Nasr ◽  
V. Deretic
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Knockout Mice ◽  
Respiratory Infections ◽  
Bacterial Colonization ◽  
Interleukin 10 ◽  
High Morbidity ◽  
Necrosis Factor Alpha ◽  
Pulmonary Clearance ◽  
Tnf Α

ABSTRACT Cystic fibrosis (CF) is characterized by dysfunction of the digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections. Chronic lung infections withPseudomonas aeruginosa, intense neutrophil-dominated airway inflammation, and progressive lung disease are the major cause of high morbidity and mortality in CF. Here we investigated the effects of malnutrition in CF on innate lung defenses, susceptibility to P. aeruginosa colonization, and associated inflammation, using aerosol models of acute and chronic infections in normal, malnourished, and transgenic mice. CFTRm1Unc−/− knockout mice displayed body weight variations and showed variable pulmonary clearance of P. aeruginosa. This variability was not detected in bitransgenicCFTRm1Unc−/− (FABP-hCFTR) mice in which the intestinal defect had been corrected. Diet-induced protein calorie malnutrition in C57BL/6J mice resulted in impaired pulmonary clearance of P. aeruginosa. Tumor necrosis factor alpha (TNF-α) and nitrite levels detected upon exposure to P. aeruginosaaerosols were lower in the lungs of the malnourished C57BL/6J mice relative than in lungs of mice fed a normal diet. The role of TNF-α and reactive nitrogen intermediates in P. aeruginosaclearance was tested in TNF-α and inducible nitric oxide synthase (iNOS) knockout mice. P. aeruginosa clearance was diminished in transgenic TNF-α- and iNOS-deficient mice. In contrast to the effects of TNF-α and iNOS, gamma interferon knockout mice retained a full capacity to eliminate P. aeruginosafrom the lung. Malnutrition also contributed to excessive inflammation in C57BL/6J mice upon chronic challenge with P. aeruginosa. The repeatedly infected malnourished host did not produce interleukin-10, a major anti-inflammatory cytokine absent or diminished in the bronchoalveolar fluids of CF patients. These results are consistent with a model in which defective CFTR in the intestinal tract leads to nutritional deficiency which in turn contributes to compromised innate lung defenses, bacterial colonization, and excessive inflammation in the CF respiratory tract.

scholarly journals The Furin Inhibitor Hexa-d-Arginine Blocks the Activation of Pseudomonas aeruginosa Exotoxin A In Vivo

2002 ◽  
Vol 70 (12) ◽  
pp. 7136-7139 ◽  
Author(s):  
Miroslav S. Sarac ◽  
Angus Cameron ◽  
Iris Lindberg
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Survival Rate ◽  
Tumor Necrosis ◽  
Exotoxin A ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Pseudomonas Aeruginosa Exotoxin ◽  
Circulating Levels ◽  
Necrosis Factor

ABSTRACT The Pseudomonas aeruginosa exotoxin A (PEA) protein requires furin-mediated cleavage for manifestation of toxicity. We show here that the small stable furin inhibitor hexa-d-arginine amide effectively blocks PEA-induced cell lysis and is itself noncytotoxic. Administration of hexa-d-arginine to PEA-treated mice significantly improves their survival rate and also decreases circulating levels of tumor necrosis factor alpha.

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