Complement activation-related pseudoallergy: A new class of drug-induced acute immune toxicity

Toxicology ◽  
2005 ◽  
Vol 216 (2-3) ◽  
pp. 106-121 ◽  
Author(s):  
Janos Szebeni
Keyword(s):  
Complement Activation ◽  
Drug Induced ◽  
New Class ◽  
Immune Toxicity

Abstract 15043: Circulating microRNA as Novel Biomarkers of Doxorubicin Induced Cardiotoxicity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuri D’Alessandra ◽  
Marta Pontremoli ◽  
Giuseppina Milano ◽  
Alessandro Scopece ◽  
Giulio Pompilio ◽  
...  
Keyword(s):  
Disease Onset ◽  
Recovery Phase ◽  
Circulating Microrna ◽  
Circulating Biomarkers ◽  
Circulating Mirnas ◽  
Drug Induced ◽  
Heart Dysfunction ◽  
New Class ◽  
Novel Biomarkers ◽  
Circulating Levels

Background: Cardiotoxicity is a well-known side effect of Doxorubicin (Dox), leading to drug-induced heart dysfunction. Early prediction of disease onset is difficult, thus a new class of heart impairment biomarkers is needed. A role for miRNAs as circulating biomarkers of Dox-mediated heart dysfunction has never been tested. Purpose: To identify differentially expressed circulating miRNAs of early and late Dox-induced cardiotoxicity using an animal model. Methods: Healthy mice were administered 24 mg/Kg cumulative dose of Dox during a period of 2 weeks followed by 2-month recovery. Cardiotoxicity insurgence was detectable by echocardiography as early as 1 week after treatment. The expression of 367 miRNAs was analyzed in plasma samples from treated and untreated animals (n=6/group) at the end of the treatment (2 weeks) and 2 months post-administration (recovery phase) followed by singleplex qPCR validation of all miRNAs of interest. Results: We identified 5 Dox-regulated miRNAs of acute phase. MiR-34a, -34c, and -133a showed an upregulation (6.5, 14.9, and 15 folds, respectively, p≤0.01), whereas miR-16 and miR-451 were negatively regulated by the drug (-2.7 and -2.8 folds, respectively, p<0.05). We then investigated the expression of these miRNAs 2 months after the end of the treatment, but none showed a significant modulation. Conversely, miR-326 was positively regulated by Dox in the plasma of mice after 2 months of recovery (1.53 folds, p<0.05). Conclusions: This is the first study investigating the possible use of circulating miRNAs as biomarkers of both early and post-treatment Dox-induced cardiotoxicity. Our results revealed a strong regulation of 5 plasmatic miRNAs in response to early damage. Early responders returned to basal levels of expression 2 months after drug administration, indicating an acute damage induced release. This prompts for further studies in the clinical setting to test their suitability as toxicity markers beside cardiac troponin. By contrast, we could not identify strong markers of late damage, apart from a marginal difference in miR-326 circulating levels.

Development of a New Class of Nanoparticles which Avoid Phagocytosis by Inhibiting Complement Activation

1998 ◽  
pp. 241-251
Author(s):  
Catherine Passirani ◽  
Gillian Barratt ◽  
Jean-Philippe Devissaguet ◽  
Denis Labarre
Keyword(s):  
Complement Activation ◽  
New Class

Homologous complement activation on drug-induced apoptotic cells from a human lung adenocarcinoma cell line

Immunobiology ◽  
1997 ◽  
Vol 196 (5) ◽  
pp. 491-503 ◽  
Author(s):  
Tomoko Hara ◽  
Misako Matsumoto ◽  
Shotaro Tsuji ◽  
Shigeharu Nagasawa ◽  
Akira Hiraoka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Complement Activation ◽  
Human Lung ◽  
Adenocarcinoma Cell Line ◽  
Drug Induced ◽  
Adenocarcinoma Cell ◽  
Human Lung Adenocarcinoma ◽  
Lung Adenocarcinoma Cell Line ◽  
Human Lung Adenocarcinoma Cell

scholarly journals Neglected, Drug-Induced Platinum Accumulation Causes Immune Toxicity

2020 ◽  
Vol 11 ◽  
Author(s):  
Yuling Zhang ◽  
Jieting Zheng ◽  
Yi Jiang ◽  
Xuchun Huang ◽  
Ling Fang
Keyword(s):  
Drug Induced ◽  
Platinum Accumulation ◽  
Immune Toxicity

Piezoresistive sensor-integrated PDMS cantilever: A new class of device for measuring the drug-induced changes in the mechanical activity of cardiomyocytes

2017 ◽  
Vol 240 ◽  
pp. 566-572 ◽  
Author(s):  
Dong-Su Kim ◽  
Yun-Jin Jeong ◽  
Bong-Kee Lee ◽  
Arunkumar Shanmugasundaram ◽  
Dong-Weon Lee
Keyword(s):  
Mechanical Activity ◽  
Drug Induced ◽  
New Class ◽  
Piezoresistive Sensor ◽  
Induced Changes

Comparison of complement activation-related pseudoallergy in miniature and domestic pigs: foundation of a validatable immune toxicity model

2016 ◽  
Vol 12 (4) ◽  
pp. 933-943 ◽  
Author(s):  
Joshua A. Jackman ◽  
Tamás Mészáros ◽  
Tamás Fülöp ◽  
Rudolf Urbanics ◽  
Janos Szebeni ◽  
...  
Keyword(s):  
Complement Activation ◽  
Domestic Pigs ◽  
Immune Toxicity

scholarly journals Drug-induced ion channel opening tuned by the voltage sensor charge profile

2014 ◽  
Vol 143 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Nina E. Ottosson ◽  
Sara I. Liin ◽  
Fredrik Elinder
Keyword(s):  
Small Molecule ◽  
Voltage Sensor ◽  
K Channel ◽  
Detailed Knowledge ◽  
Drug Induced ◽  
New Class ◽  
Channel Opening ◽  
Future Drug ◽  
Small Molecule Compound ◽  
Voltage Gated Ion Channels

Polyunsaturated fatty acids modulate the voltage dependence of several voltage-gated ion channels, thereby being potent modifiers of cellular excitability. Detailed knowledge of this molecular mechanism can be used in designing a new class of small-molecule compounds against hyperexcitability diseases. Here, we show that arginines on one side of the helical K-channel voltage sensor S4 increased the sensitivity to docosahexaenoic acid (DHA), whereas arginines on the opposing side decreased this sensitivity. Glutamates had opposite effects. In addition, a positively charged DHA-like molecule, arachidonyl amine, had opposite effects to the negatively charged DHA. This suggests that S4 rotates to open the channel and that DHA electrostatically affects this rotation. A channel with arginines in positions 356, 359, and 362 was extremely sensitive to DHA: 70 µM DHA at pH 9.0 increased the current &gt;500 times at negative voltages compared with wild type (WT). The small-molecule compound pimaric acid, a novel Shaker channel opener, opened the WT channel. The 356R/359R/362R channel drastically increased this effect, suggesting it to be instrumental in future drug screening.

Promising Use of the New Biologics in the Management of Drug-Induced Hypersensitivity Reactions: Preliminary Approaches

2020 ◽  
Vol 20 (9) ◽  
pp. 1456-1469
Author(s):  
Gianfranco Calogiuri ◽  
Knut Brockow ◽  
Eustachio Nettis ◽  
Luigi Macchia ◽  
Caterina Foti ◽  
...  
Keyword(s):  
Drug Hypersensitivity ◽  
Cellular Level ◽  
Hypersensitivity Reactions ◽  
Drug Induced ◽  
Off Label ◽  
Immunological Responses ◽  
New Class ◽  
Immunological Mechanisms ◽  
Factor Α ◽  
Necrosis Factor

Biologics are an innovative class of drugs that can selectively influence immunological responses at a cellular level. Although their use is usually restricted to some specific diseases, such as autoimmune pathologies and tumors, their “off-label” administration has increased widely in the last years. Drug treatment may induce hypersensitivity reactions which currently lack any gold standard therapy but maybe a future field of application for biologics. Agents like anti-IgE (Omalizumab) and Tumor Necrosis Factor-α inhibitors might be used in immediate-type and cell-mediated hypersensitivity caused by medications, respectively, and the first trials in that direction are being reported in the literature. In fact, the refined immunological mechanisms involved in the pathogenesis of drug hypersensitivity might respond successfully to this new class of drugs.

scholarly journals Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 104-110 ◽  
Author(s):  
Bo Zhang ◽  
Qin Li ◽  
Chenyang Shi ◽  
Xinyue Zhang
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Complement Activation ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Drug Reactions ◽  
Lethal Outcome ◽  
Drug Induced ◽  
Opioid Drugs ◽  
Inflammatory Drugs

Adverse drug reactions occur frequently and can trigger pseudoallergy, which has become a serious threat to public health. Pseudoallergy is a typical non-immune anaphylactic reaction characterized by the independence of antigen-specific immune responses. In the clinic, pseudoallergy is often elicited by the first dose of medication, and here lies its unpredictability and occasional lethal outcome. However, the mechanisms of pseudoallergy are not well understood. This review focusses on the causes and mechanisms of pseudoallergy induced by drugs. Two categories of mechanisms will be considered, namely, (1) complement activation-related pseudoallergy and (2) mast cell activation-related pseudoallergy. The factors that induce pseudoallergy include opioid drugs, complement activation-related pseudoallergenic drugs, nonsteroidal anti-inflammatory drugs and traditional Chinese medicine injections.

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