scholarly journals In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

1999 ◽  
Vol 43 (5) ◽  
pp. 1091-1097 ◽  
Author(s):  
Hideki Kita ◽  
Hirotami Matsuo ◽  
Hitomi Takanaga ◽  
Junichi Kawakami ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Threshold Concentration ◽  
Current Response ◽  
Drug Induced ◽  
Inhibition Ratio ◽  
New Quinolones ◽  
The Central Nervous System ◽  
Anti Inflammatory

ABSTRACT We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the γ-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 μM) > FRP (0.3 μM) > FLB (0.2 μM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

1999 ◽  
Vol 43 (8) ◽  
pp. 2101-2101
Author(s):  
Hideki Kita ◽  
Hirotami Matsuo ◽  
Hitomi Takanaga ◽  
Junichi Kawakami ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Induced ◽  
Inflammatory Drug ◽  
The Central Nervous System ◽  
Anti Inflammatory

scholarly journals Early-Released Interleukin-10 Significantly Inhibits Lipopolysaccharide-Elicited Neuroinflammation In Vitro

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2173
Author(s):  
Yubao Wang ◽  
Pei Yu ◽  
Yi Li ◽  
Zhan Zhao ◽  
Xiaomei Wu ◽  
...  
Keyword(s):  
Late Phase ◽  
Interleukin 10 ◽  
Glial Cultures ◽  
Pilot Investigation ◽  
The Central Nervous System ◽  
Β2 Adrenergic Receptor ◽  
Anti Inflammatory ◽  
Protein Assays

Anti-inflammatory cytokine interleukin (IL)-10 is pivotal for limiting excessive inflammation in the central nervous system. Reports show that lipopolysaccharide (LPS)-induced microglial IL-10 emerges in a delayed manner in vitro and in vivo, lagging behind proinflammatory cytokines to facilitate the resolution of neuroinflammation. We hypothesized that IL-10 releases quite quickly based on our pilot investigation. Here, we uncovered a bimodal expression of microglial IL-10 gene transcription induced by LPS in mouse primary mixed glial cultures. This pattern consisted of a short brief early-phase and a long-lived late-phase, enabling the production of IL-10 protein in a rapid manner. The removal and addition of IL-10 protein assays indicated that early-released IL-10 exerted potent modulatory effects on neuroinflammation at picomolar levels, and IL-10 released at the onset of neuroinflammation is tightly controlled. We further showed that the early-released, but not the late-released, IL-10 was crucial for mediating and potentiating the anti-inflammatory function of a β2-adrenergic receptor agonist salmeterol. This study in vitro highlights the essential role of early-released IL-10 in regulating the appropriate degree of neuroinflammation, overturning the previous notion that microglial IL-10 produces and functions in a delayed manner and providing new insights into anti-inflammatory mechanisms-mediated neuroimmune homeostasis.

scholarly journals Pure Total Flavonoids From Citrus Protect Against Nonsteroidal Anti-inflammatory Drug-Induced Small Intestine Injury by Promoting Autophagy in vivo and in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Chen ◽  
Jianping Jiang ◽  
Guanqun Chao ◽  
Xiaojie Hong ◽  
Haijun Cao ◽  
...  
Keyword(s):  
Small Intestine ◽  
Western Blotting ◽  
Intestinal Barrier ◽  
Total Flavonoids ◽  
Protective Effects ◽  
Drug Induced ◽  
Expression Levels ◽  
Anti Inflammatory

Small intestine injury is an adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) that urgently needs to be addressed for their safe application. Although pure total flavonoids from citrus (PTFC) have been marketed for the treatment of digestive diseases, their effects on small intestine injury and the underlying mechanism of action remain unknown. This study aimed to investigate the potential role of autophagy in the mechanism of NSAID (diclofenac)-induced intestinal injury in vivo and in vitro and to demonstrate the protective effects of PTFC against NSAID-induced small intestine disease. The results of qRT-PCR, western blotting, and immunohistochemistry showed that the expression levels of autophagy-related 5 (Atg5), light chain 3 (LC3)-II, and tight junction (TJ) proteins ZO-1, claudin-1, and occludin were decreased in rats with NSAID-induced small intestine injury and diclofenac-treated IEC-6 cells compared with the control groups. In the PTFC group, Atg5 and LC3-II expression, TJ protein expression, and the LC3-II/LC3-I ratio increased. Furthermore, the mechanism by which PTFC promotes autophagy in vivo and in vitro was evaluated by western blotting. Expression levels of p-PI3K and p-Akt increased in the intestine disease-induced rat model group compared with the control, but decreased in the PTFC group. Autophagy of IEC-6 cells was upregulated after treatment with a PI3K inhibitor, and the upregulation was significantly more after PTFC treatment, suggesting PTFC promoted autophagy through the PI3K/Akt signaling pathway. In conclusion, PTFC protected intestinal barrier integrity by promoting autophagy, which demonstrates its potential as a therapeutic candidate for NSAID-induced small intestine injury.

scholarly journals TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation

2021 ◽  
Vol 22 (21) ◽  
pp. 11576
Author(s):  
David A. Barnes ◽  
Dylan A. Galloway ◽  
Marius C. Hoener ◽  
Mark D. Berry ◽  
Craig S. Moore
Keyword(s):  
Brain Tissue ◽  
Nuclear Localization ◽  
Demyelinating Disease ◽  
Border Region ◽  
Human Macrophages ◽  
Immune Mediated ◽  
Inflammatory Activation ◽  
The Central Nervous System

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.

scholarly journals Macrophages Modulate Hepatic Injury Involving NLRP3 Inflammasome: The Example of Efavirenz

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 109
Author(s):  
Fernando Alegre ◽  
Alberto Martí-Rodrigo ◽  
Miriam Polo ◽  
Dolores Ortiz-Masiá ◽  
Celia Bañuls ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Cell ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Cell Types ◽  
Drug Induced ◽  
Anti Inflammatory

Drug-induced liver injury (DILI) constitutes a clinical challenge due to the incomplete characterization of the mechanisms involved and potential risk factors. Efavirenz, an anti-HIV drug, induces deleterious actions in hepatocytes that could underlie induction of the NLRP3 inflammasome, an important regulator of inflammatory responses during liver injury. We assessed the potential of efavirenz to modulate the inflammatory and fibrogenic responses of major liver cell types involved in DILI. The effects of efavirenz were evaluated both in vitro and in vivo. Efavirenz triggered inflammation in hepatocytes, in a process that involved NF-κB and the NLRP3 inflammasome, and activated hepatic stellate cells (HSCs), thereby enhancing expression of inflammatory and fibrogenic markers. The NLRP3 inflammasome was not altered in efavirenz-treated macrophages, but these cells polarized towards the anti-inflammatory M2 phenotype and displayed upregulated anti-inflammatory mediators. Conversely, no evidence of damage was observed in efavirenz-treated animals, except when macrophages were depleted, which resulted in the in vivo manifestation of the deleterious effects detected in hepatocytes and HSCs. Efavirenz elicits a cell-specific activation of the NLRP3 inflammasome in hepatocytes and HSCs, but macrophages appear to counteract efavirenz-induced liver injury. Our results highlight the dynamic nature of the interaction among liver cell populations and emphasize the potential of targeting macrophage polarization as a strategy to treat NLRP3 inflammasome-induced liver injury.

In vitro and in vivo evaluation of the anti-inflammatory effects of Arzanol from Helichrysum italicum

Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
Anti Inflammatory

Haemanthus coccineus extract shows profound anti-inflammatory actions in vitro and in vivo due to its main alkaloid narciclasine

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
S Fuchs ◽  
LT Hsieh ◽  
W Saarberg ◽  
CAJ Erdelmeier ◽  
TA Wichelhaus ◽  
...  
Keyword(s):  
Anti Inflammatory

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

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