PhD Scientific Days 2020

Theoretical and Translational I. Posters

Symptoms and Mechanisms of Nanoparticulate-induced Pseudoallergy in Mice

Előadó neve

Dr. Őrfi, Erik

Előadó munkahelye

Translational Medicine

Előadó telefonszáma

+36306264883

Előadó e-mail címe

rickrster@gmail.com

Az előadás címe

Symptoms and Mechanisms of Nanoparticulate-induced Pseudoallergy in Mice

Szerző(k) neve és munkahelye

Erik Őrfi1, Tamás Mészáros2, János Szebeni1,2 and Gábor Szénási1,2

1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; 2SeroScience LCC., Budapest, Hungary

Szekció

Theoretical and Translational I. Posters

Language of the presentation

English

Section, first choice

Pharmaceutical Sciences

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: A new promising direction in medicine is the use of nanoparticulate vehicles for controlled, targeted drug delivery. However, an unsolved problem is that nanomedicines can cause IgE-independent side effects known as infusion reaction, pseudoallergy or anaphylactic reaction.

Aims: We aimed to characterize the symptoms and basic mechanisms of pseudoallergy caused by intravenous injection of amphotericin B containing liposomes (AmBisome, 300 mg/kg; Abelcet, 30 mg/kg), polystyrene nanoparticles (NP, 500 nm, 26 mg/kg), as well as direct complement (C) activators, zymosan (ZY, 30 mg/kg) and cobra venom factor (CVF, 100 U/kg) in mice.

Methods: The carotid artery and jugular vein were cannulated in anesthetized (pentobarbital, 90 mg/kg i.p.) male NMRI mice (n=5-7/group), and also in wild type (WT), thromboxane prostanoid receptor deficient (TP KO) mice on C57Bl/6 background, and blood pressure (BP) was recorded. Blood was collected from other groups of NMRI mice at 3-5 min after treatments, and plasma C3a and thromboxane B2 (TXB2) concentrations were assayed using ELISA. Blood count was carried out in Abacus vet5 hematology analyzer.

Results: All treatments caused an initial hypertension lasting for 3-5 min, while BP returned to baseline after administration of liposomes and NP but progressed to hypotensive shock after treatment with direct C activators. All treatments decreased leukocyte and platelet counts, increased hematocrit and plasma C3a and TXB2 concentrations. However, direct C activators caused much greater changes in plasma C3a concentrations than nanoparticles. Pretreatment with SB290157 (10 mg/kg, i.v.), a C3a receptor antagonist, attenuated the hypertensive response to Abelcet and led to delayed hypotension, while DF2593A (1 mg/kg, i.v.), a C5a receptor antagonist, considerably lengthened the hypertensive effect of Abelcet. Abelcet caused hypotension only in TP KO mice.

Conclusion: Blood pressure and hematological changes are the main symptoms of nanoparticulate-induced pseudoallergy in mice, which seemed to be caused at least in part by complement activation and consecutive thromboxane secretion leading to hypertension. The detailed mechanisms of hypotensive effect remain to be elucidated.

Additional Information

Gabor Szénási: szenasi.gabor@med.semmelweis-univ.hu
János Szebeni: jszebeni2@gmail.com

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4713

Start

11:35

End

11:38

Authors (legacy)

Erik Őrfi1, Tamás Mészáros2, János Szebeni1,2 and Gábor Szénási1,2

1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; 2SeroScience LCC., Budapest, Hungary