Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum

2015 ◽  
Vol 309 (4) ◽  
pp. F318-F331 ◽  
Author(s):  
Keh-Min Liu ◽  
Shu-Mien Chuang ◽  
Cheng-Yu Long ◽  
Yi-Lun Lee ◽  
Chao-Chuan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Antioxidant Enzymes ◽  
Tight Junction ◽  
Er Stress ◽  
Tight Junction Proteins ◽  
Stress Markers ◽  
Bladder Cell ◽  
Associated Proteins ◽  
Junction Proteins

Ketamine abusers develop severe lower urinary tract symptoms. The major aims of the present study were to elucidate ketamine-induced ulcerative cystitis and bladder apoptosis in association with oxidative stress mediated by mitochondria and the endoplasmic reticulum (ER). Sprague-Dawley rats were distributed into three different groups, which received normal saline or ketamine for a period of 14 or 28 days, respectively. Double-labeled immunofluorescence experiments were performed to investigate tight junction proteins for urothelial barrier functions. A TUNEL assay was performed to evaluate the distribution of apoptotic cells. Western blot analysis was carried out to examine the expressions of urothelial tight junction proteins, ER stress markers, and apoptosis-associated proteins. Antioxidant enzymes, including SOD and catalase, were investigated by real-time PCR and immunofluorescence experiments. Ketamine-treated rats were found to display bladder hyperactivity. This bladder dysfunction was accompanied by disruptions of epithelial cadherin- and tight junction-associated proteins as well as increases in the expressions of apoptosis-associated proteins, which displayed features of mitochondria-dependent apoptotic signals and ER stress markers. Meanwhile, expressions of mitochondria respiratory subunit enzymes were significantly increased in ketamine-treated bladders. Conversely, mRNA expressions of the antioxidant enzymes Mn-SOD (SOD2), Cu/Zn-SOD (SOD1), and catalase were decreased after 28 days of ketamine treatment. These results demonstrate that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and ER-dependent pathways and consequently contributed to bladder apoptosis and urothelial lining defects. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects are potential factors that may play a crucial role in bladder overactivity and ulceration.

scholarly journals The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction

2010 ◽  
Vol 298 (5) ◽  
pp. G625-G633 ◽  
Author(s):  
Wei Zhong ◽  
Craig J. McClain ◽  
Matthew Cave ◽  
Y. James Kang ◽  
Zhanxiang Zhou
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Zinc Deficiency ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Alcohol Exposure ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Junction Proteins

Disruption of the intestinal barrier is a causal factor in the development of alcoholic endotoxemia and hepatitis. This study was undertaken to determine whether zinc deficiency is related to the deleterious effects of alcohol on the intestinal barrier. Mice were pair fed an alcohol or isocaloric liquid diet for 4 wk, and hepatitis was detected in association with elevated blood endotoxin level. Alcohol exposure significantly increased the permeability of the ileum but did not affect the barrier function of the duodenum or jejunum. Reduction of tight-junction proteins at the ileal epithelium was detected in alcohol-fed mice although alcohol exposure did not cause apparent histopathological changes. Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species. Caco-2 cell culture demonstrated that alcohol exposure increases the intracellular free zinc because of oxidative stress. Zinc deprivation caused epithelial barrier disruption in association with disassembling of tight junction proteins in the Caco-2 monolayer cells. Furthermore, minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. In conclusion, epithelial barrier dysfunction in the distal small intestine plays an important role in alcohol-induced gut leakiness, and zinc deficiency attributable to oxidative stress may interfere with the intestinal barrier function by a direct action on tight junction proteins or by sensitizing to the effects of alcohol.

scholarly journals Effect of Probiotics on the Performance and Intestinal Health of Broiler Chickens Infected with Eimeria tenella

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Muhammad Mohsin ◽  
Ziping Zhang ◽  
Guangwen Yin
Keyword(s):  
Immune Response ◽  
Antioxidant Enzymes ◽  
Tight Junction ◽  
Humoral Immune Response ◽  
Eimeria Tenella ◽  
Serum Chemistry ◽  
Tight Junction Proteins ◽  
Humoral Immune ◽  
Significant Difference ◽  
Junction Proteins

Coccidiosis is an important parasitic disease of poultry with great economic importance. Due to drug resistance issues, the study was conducted to investigate how probiotics (Lactobacillus plantarum or L. plantarum) affected oocysts per gram of feces (OPG), fecal scores, feed conversion ratio (FCR), immunomodulatory effect in terms of the cell-mediated and humoral immune response. Serum chemistry (ALT, AST, LDH, and creatinine) was measured in different treated chicken groups. mRNA expression levels of antioxidant enzymes (SOD 1 and CAT), peptide transporter 1 (PepT 1), and tight junction proteins (ZO and CLDN 1) were also examined in chicken groups infected with Eimeria tenella (E. tenella). Chickens supplemented with L. plantarum 1 × 108 CFU (colony-forming unit) showed an improved cell-mediated and humoral immune response, compared with the control group (p < 0.05). Probiotics also enhanced the performance of antioxidant enzymes, PepT 1, and tight junction proteins, and improved serum chemistry (AST, ALT, and LDH), compared with control-infected, non-medicated chickens. However, no significant difference (p > 0.05) was observed in CLDN 1 expression level and creatinine in all treated chicken groups. These findings demonstrated that probiotics supplementation in the feed can protect the birds against E. tenella infection.

scholarly journals Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1α Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 820 ◽  
Author(s):  
Donghyun Kim ◽  
Kyeong-A Kim ◽  
Jeong-Hyeon Kim ◽  
Eun-Hye Kim ◽  
Ok-Nam Bae
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Tight Junction ◽  
Reactive Oxygen ◽  
Mitochondrial Damage ◽  
Oxygen Species ◽  
Brain Endothelial Cells ◽  
Tight Junction Proteins ◽  
Junction Proteins

Methylglyoxal (MG) is a dicarbonyl compound, the level of which is increased in the blood of diabetes patients. MG is reported to be involved in the development of cerebrovascular complications in diabetes, but the exact mechanisms need to be elucidated. Here, we investigated the possible roles of oxidative stress and mitophagy in MG-induced functional damage in brain endothelial cells (ECs). Treatment of MG significantly altered metabolic stress as observed by the oxygen-consumption rate and barrier-integrity as found in impaired trans-endothelial electrical resistance in brain ECs. The accumulation of MG adducts and the disturbance of the glyoxalase system, which are major detoxification enzymes of MG, occurred concurrently. Reactive oxygen species (ROS)-triggered oxidative damage was observed with increased mitochondrial ROS production and the suppressed Akt/hypoxia-inducible factor 1 alpha (HIF-1α) pathway. Along with the disturbance of mitochondrial bioenergetic function, parkin-1-mediated mitophagy was increased by MG. Treatment of N-acetyl cysteine significantly reversed mitochondrial damage and mitophagy. Notably, MG induced dysregulation of tight junction proteins including occludin, claudin-5, and zonula occluden-1 in brain ECs. Here, we propose that diabetic metabolite MG-associated oxidative stress may contribute to mitochondrial damage and autophagy in brain ECs, resulting in the dysregulation of tight junction proteins and the impairment of permeability.

Abstract 3754: Homocysteine Induces Alternations Of Tight Junction Proteins In Brain Endothelial Cells.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Neetu Tyagi ◽  
Natia Qipshidze ◽  
Srikanth Givvimani ◽  
Paras K Mishra ◽  
David Lominadze ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Tight Junction ◽  
Kinase Inhibitors ◽  
Mitogen Activated Protein Kinase ◽  
High Dose ◽  
Tight Junction Proteins ◽  
Filamentous Actin ◽  
Mek Kinase ◽  
Junction Proteins

Hyperhomocysteinmia (HHcy) is associated with neurological disorders (Stroke, Alzheimer, Parkinson etc) and causes blood brain barrier (BBB) dysfunction. We previously showed that an elevated level of homocysteine (Hcy) increased formation of filamentous actin and enhanced endothelial layer permeability. In the present work we tested the hypothesis that Hcy induces oxidative stress and binding to endothelial cells (ECs) alters expression of endothelial tight junction proteins (TJP). In this study mouse brain microvascular endothelial cells (bEND3) were grown in gold plated chambers of an electrical cell-substrate impedance system, 8-well chambered. Confluent bEND3 were treated with different doses of Hcy with mitogen-activated protein kinase (MEK) kinase inhibitors (PD98059 or U0126) or H 2 O 2 (oxidant), or medium alone for 24 h. Reactive oxygen species (ROS) was detected using DCFH-DA assay. Hcy induced a dose-dependent decrease in EC junction integrity as determined by transendothelial electrical resistance (TEER). Our results show that high dose of Hcy induces oxidative stress, which cause down regulation of the TJPs contents occludin, zona occluden-1 (ZO-1), and zona occluden-2 (ZO-2) in bEND3s. Hcy-induced decreases in contents of the TJPs were blocked by PD98059, U0126. While BQ788 inhibited endothelin-1-induced decrease in TEER, it did not affect Hcy-induced decrease in TEER. These data suggest that Hcy increases EC layer permeability via the MEK kinase signaling pathway by affecting TJPs, which are bound to actin filaments. Therefore, increased binding of Hcy with ECs during cerebo-vascular diseases may increase microvascular permeability by altering the content and possibly subcellular localization of endothelial TJPs.

scholarly journals Neuroprotective Effects of dl-3-n-Butylphthalide against Doxorubicin-Induced Neuroinflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Behavioral Changes

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Dehua Liao ◽  
Daxiong Xiang ◽  
Ruili Dang ◽  
Pengfei Xu ◽  
Jiemin Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Therapeutic Potential ◽  
Interleukin 1 ◽  
Behavioral Changes ◽  
Anxiety And Depression ◽  
Stress Markers ◽  
Neural Apoptosis

Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited due to its neurobiological side effects associated with depression. We investigated the neuroprotective efficacy of dl-3-n-butylphthalide (dl-NBP) against DOX-induced anxiety- and depression-like behaviors in rats. dl-NBP was given (30 mg/kg) daily by gavage over three weeks starting seven days before DOX administration. Elevated plus maze (EPM) test, forced swimming test (FST), and sucrose preference test (SPT) were performed to assess anxiety- and depression-like behaviors. Our study showed that the supplementation of dl-NBP significantly mitigated the behavioral changes induced by DOX. To further explore the mechanism of neuroprotection induced by dl-NBP, several biomarkers including oxidative stress markers, endoplasmic reticulum (ER) stress markers, and neuroinflammatory cytokines in the hippocampus were quantified. The results showed that dl-NBP treatment alleviated DOX-induced neural apoptosis. Meanwhile, DOX-induced oxidative stress and ER stress in the hippocampus were significantly ameliorated in dl-NBP pretreatment group. Our study found that dl-NBP alleviated the upregulation of malondialdehyde (MDA), nitric oxide (NO), CHOP, glucose-regulated protein 78 kD (GRP-78), and caspase-12 and increased the levels of reduced glutathione (GSH) and activities of catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in the hippocampus of rats exposed to DOX. Additionally, the gene expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) and protein levels of inducible nitric oxide synthase (iNOS) were significantly increased in DOX-treated group, whereas DOX-induced neuroinflammation was significantly attenuated in dl-NBP supplementation group. In conclusion, dl-NBP could alleviate DOX-induced anxiety- and depression-like behaviors via attenuating oxidative stress, ER stress, inflammatory reaction, and neural apoptosis, providing a basis as a therapeutic potential against DOX-induced neurotoxicity.

scholarly journals Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

2016 ◽  
Vol 7 ◽  
pp. 675-684 ◽  
Author(s):  
Yue Zhang ◽  
Wan-Xi Yang
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Blood Vessels ◽  
Food Additives ◽  
Negative Influence ◽  
Potential Mechanism ◽  
Tight Junction Proteins ◽  
Zonula Occludens ◽  
Therapy And Diagnosis ◽  
Junction Proteins

Since nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens)) proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

Effects of bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate on liver injury in Balb/c mice

2021 ◽  
Vol 37 (9) ◽  
pp. 547-554
Author(s):  
Jing Yin ◽  
Bao Zhang
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Human Exposure ◽  
Protective Role ◽  
Hepatic Damage ◽  
Oral Exposure ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Associated Proteins

Bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) has been used as a replacement in some commercial flame-retardant mixtures. It is widely used in industrial products, so the probability of human exposure to TBPH is high. Yet, little is known about how it is metabolized or its toxicity. To this end, we investigated what effect oral exposure of Balb/c mice to TBPH at concentrations of 200 mg kg−1 had on hepatic damage. Staining results showed liver injury in the mice exposed to TBPH. Oxidative stress markers and endoplasmic reticulum stress associated proteins were altered in the TBPH exposed mice, and these changes could be attenuated by administration of curcumin at 25 mg kg−1. Overall, TBPH induces hepatic damage via increasing oxidative stress, and curcumin plays a protective role in alleviating the TBPH-mediated histopathological alterations in the liver.

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