Multifunctional Molecule, JM-20, Reverses Aluminum Chloride-Induced Memory Impairment and Neuronal Damage in Rats

2021 ◽  
Author(s):  
Maylin Wong-Guerra ◽  
Yanay Montano-Peguero ◽  
Jeney Ramírez-Sánchez ◽  
Javier Jiménez-Martin ◽  
Luis Arturo Fonseca-Fonseca ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
New Drugs ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Memory Decline ◽  
Cholinergic Dysfunction ◽  
Potential Capacity ◽  
Factor Alpha ◽  
High Oxidative Stress ◽  
Related Proteins

Abstract Alzheimer's disease (AD) is a neurodegenerative disease that worsens with aging. Today, there is a worldwide effort to find new drugs that could delay the onset, slow the progression, or improve symptoms of AD. Oral administration of aluminum to rodents recapitulates some pathological alterations observed in AD, being considered a convenient tool for modeling and testing the efficacy of new therapeutics. Our previous studies have shown that JM-20, a dihydropyridine and benzodiazepine hybrid molecule protected memory in an environment with cholinergic dysfunction, high oxidative stress, hyperactivation of acetylcholinesterase (AChE) enzyme, and mitochondrial damage produced by scopolamine. In order to gain further insight into the effects on JM-20 on AD pathology, we evaluated the protective effects of JM-20 after chronic AlCl3 administration to rats, and assessed several types of episodic memory alterations and associated-pathological mechanisms, including mitochondrial dysfunction, AChE hyperactivity, inflammation, and apoptosis-related proteins. We used behavioral tasks to test spatial, working an emotional- associative memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study showed that JM-20 prevented memory decline alongside with the inhibition of aluminum-induced alterations of oxidative parameters, and increase of AChE activity and of tumor necrosis factor alpha (TNF-α) levels. JM-20 also preserved anti-apoptotic proteins and protected against axonal and neuronal damaged in the hippocampus and prefrontal cortex. Altogether, our findings expanded our understanding of the ability of JM-20 to preserve essential types of memory in rats under neurotoxic conditions, and suggest its potential capacity to counteract etiological factors of AD by breaking the progression of key neurodegeneration-associated steps in a rat model of the disease.

scholarly journals Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

2017 ◽  
Vol 95 (7) ◽  
pp. 866-872 ◽  
Author(s):  
Erdem Kamil Ozer ◽  
Mustafa Tugrul Goktas ◽  
Ibrahim Kilinc ◽  
Aysun Toker ◽  
Hulagu Bariskaner ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Organ Damage ◽  
Multiple Organ ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Mesenteric Perfusion ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.

scholarly journals Resveratrol Modulates Phagocytosis of Bacteria through an NF-κB-Dependent Gene Program

2007 ◽  
Vol 52 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Mitsuhiro Iyori ◽  
Hideo Kataoka ◽  
Haque Mohammad Shamsul ◽  
Kazuto Kiura ◽  
Motoaki Yasuda ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Hek293 Cells ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Lectin Receptors ◽  
Macrophage Scavenger Receptor ◽  
Toll Like Receptor 2 ◽  
Factor Alpha

ABSTRACT Many studies have shown that the pharmacological effects of resveratrol, a phytoalexin polyphenolic compound, include protective effects against cancer and inflammation as well as enhancement of stress resistance. In this study, we examined whether resveratrol affected the phagocytosis of bacteria by macrophages and the activation of the transcription factor NF-κB after stimulation with or without the ligand FSL-1 for Toll-like receptor 2 (TLR2). Phagocytosis of Escherichia coli and of Staphylococcus aureus by THP-1 cells and RAW264.7 cells was inhibited by resveratrol in a dose-dependent manner regardless of stimulation with FSL-1. The NF-κB activity in HEK293 cells stably expressing TLR2 was also inhibited by resveratrol after stimulation with FSL-1. Resveratrol also inhibited both the translocation of p65 of NF-κB into nuclei in the transfectant and tumor necrosis factor alpha production by THP-1 cells or RAW264.7 cells. It has recently been reported that TLR-mediated signaling pathways lead to the upregulation of mRNAs of phagocytic receptors, including scavenger receptors and C-type lectin receptors. This study also demonstrated that FSL-1 induced the upregulation of mRNAs of phagocytic receptors such as macrophage scavenger receptor-1, CD36, DC-SIGN, and Dectin-1 and that the FSL-1-induced upregulation of their mRNAs was inhibited by resveratrol. In addition, it was found that the expression of DC-SIGN in HEK293 cells stably expressing DC-SIGN was reduced by resveratrol and that the phagocytic activity was significantly inhibited by resveratrol. Thus, this study suggests that resveratrol inhibited bacterial phagocytosis by macrophages by downregulating the expression of phagocytic receptors and NF-κB activity.

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 Effect of Deficiency of Tumor Necrosis Factor Alpha or Both of Its Receptors on Streptococcus pneumoniae Central Nervous System Infection and Peritonitis

2001 ◽  
Vol 69 (11) ◽  
pp. 6881-6886 ◽  
Author(s):  
Andreas Wellmer ◽  
Joachim Gerber ◽  
Jasmin Ragheb ◽  
Gregor Zysk ◽  
Tammo Kunst ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Tumor Necrosis ◽  
Neuronal Damage ◽  
Central Nervous System Infection ◽  
Tnf Receptor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) and TNF-β are key mediators in bacterial inflammation. We therefore examined the role of TNF-α and its two receptors in murine pneumococcal central nervous system infection. TNF-α knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)-deficient mice and heterozygous littermates were infected intracerebrally with a Streptococcus pneumoniae type 3 strain. Mice were monitored until death or were killed 36 h after infection. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration and neuronal damage were assessed by histological scores. TNF-α-deficient mice died earlier than the controls after intracerebral infection although overall survival was similar. TNF-α deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in brain homogenates. However, it caused a substantial rise of the concentration of S. pneumoniae cells in blood and spleen. Spleen bacterial titers were also increased in p55- and p75-deficient mice. TNF receptor-deficient mice showed decreased meningeal inflammation. Neuronal damage was not affected by either TNF-α or TNF receptor deficiency. In a murine model of pneumococcal peritonitis, 102 CFU of S. pneumoniaeproduced fatal peritonitis in TNF-α-deficient, but not wild-type, mice. Early leukocyte influx into the peritoneum was impaired in TNF-α-deficient mice. The lack of TNF-α or its receptors renders mice more susceptible to S. pneumoniae infections.

scholarly journals A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes

2021 ◽  
Author(s):  
Luiz Guilherme H. S. Aragão ◽  
Júlia T. Oliveira ◽  
Jairo R. Temerozo ◽  
Mayara A. Mendes ◽  
José Alexandre Salerno ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
List Type ◽  
Protective Effects ◽  
Cardiac Damage ◽  
Necrosis Factor Alpha ◽  
Risk Of Mortality ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Human Ipsc

AbstractCoronavirus disease 2019 (COVID-19) is caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs and lead to loss of vital organ function, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, caused both directly and indirectly by SARS-CoV-2, and which is associated with a high risk of mortality. One of the hallmarks of severe COVID-19 is the “cytokine storm”, at which point the immune system malfunctions, leading to possible organ failure and death. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) on SARS-CoV-2-infected human iPSC-derived cardiomyocytes (hiPSC-CMs). Although WIN did not modulate angiotensin-converting enzyme II, nor reduced SARS-CoV-2 infection and replication in hiPSC-CMs at the conditions tested, it had anti-inflammatory and protective effects by reducing the levels of interleukins 6, 8,18 and tumor necrosis factor-alpha (TNF-α) and lactate dehydrogenase (LDH) activity in these cells without causing hypertrophic cardiac damage. These findings suggest that cannabinoids should be further investigated as an alternative therapeutic tool for the treatment of COVID-19.HighlightsHuman iPSC-derived cardiomyocytes (hiPSC-CMs) express CB1 receptor.The cannabinoid receptor agonist, WIN 55,212-2 (WIN), does not influence SARS-CoV-2 infection in hiPSC-CMs.WIN reduces inflammation and death in SARS-CoV-2-infected hiPSC-CMs.

scholarly journals Omeprazole increases survival via different mechanisms in two rat models of liver injury

2021 ◽  
Author(s):  
Masaya Kotsuka ◽  
Yuki Hashimoto ◽  
Richi Nakatake ◽  
Tetsuya Okuyama ◽  
Masahiko Hatta ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mrna Expression ◽  
Rat Hepatocytes ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Beneficial Effects ◽  
Factor Alpha ◽  
Oxide Synthase

Abstract Omeprazole (OMZ) is a proton pump inhibitor (PPI) that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of lipopolysaccharide (LPS)-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. In the in vivo models, the effects of OMZ were examined 1 h before treatment. OMZ increased survival and decreased tumor necrosis factor-alpha, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant 1, interleukin (IL)-6, and IL-1β mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. Primary rat hepatocytes were treated with IL1-β in the presence or absence of OMZ (in vitro model). OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes. Furthermore, OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.

scholarly journals Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

2017 ◽  
Vol 5 (7) ◽  
pp. 880-892 ◽  
Author(s):  
Ahmed Atwa ◽  
Rehab Hegazy ◽  
Rania Mohsen ◽  
Neamat Yassin ◽  
Sanaa Kenawy
Keyword(s):  
Hepatorenal Syndrome ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Advanced Liver Cirrhosis ◽  
Factor Alpha

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS).AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats.MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-кB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed.RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment.CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties.

scholarly journals Protection against Lipopolysaccharide-Induced Death by Fluoroquinolones

2000 ◽  
Vol 44 (11) ◽  
pp. 3169-3173 ◽  
Author(s):  
Anis A. Khan ◽  
Teri R. Slifer ◽  
Fausto G. Araujo ◽  
Yasuhiro Suzuki ◽  
Jack S. Remington
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Lethal Dose ◽  
Serum Levels ◽  
Protective Effects ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (P = 0.0001), 25% (P = 0.002), and 50% (P = 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans.

scholarly journals Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity

2018 ◽  
Vol 27 (6) ◽  
pp. 715-720 ◽  
Author(s):  
Tolga Mercantepe ◽  
Yıldıray Kalkan ◽  
Levent Tumkaya ◽  
İbrahim Sehitoglu ◽  
Filiz Mercantepe ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Pancreatic Toxicity ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Extracts from Fermented Black Garlic Exhibit a Hepatoprotective Effect on Acute Hepatic Injury

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1112 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Yi-An Chen ◽  
Jung-Tsung Wu ◽  
Kuan-Chen Cheng ◽  
Ping-Shan Lai ◽  
...  
Keyword(s):  
Hepatic Injury ◽  
Interleukin 1 ◽  
Water Layer ◽  
Hepatoprotective Effect ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Acute Hepatic Injury ◽  
Factor Alpha ◽  
Anti Inflammatory

The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl4)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl4, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl4 was injected intraperitoneally to induce AHI. The results revealed that the n-butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl4-induced acute hepatic injury.

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