Naslov
Application of sugammadex as first aid upon acute intoxication with sterigmatocystin: a proof of concept

Autori
Jakšić, Daniela ; Šegvić Klarić, Maja ; Kerep, Robert ; Piantanida, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Balkan Fungus 2022 : Abstract book / Vrioni, Georgia ; Roilides, Emmanuel - , 2022, 25-25

Skup
Balkan Fungus 2022

Mjesto i datum
Solun, Grčka, 06.10.2022. - 08.10.2022

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Sterigmatocystin ; sugammadex ; cyclodextrin ; interactions

Sažetak
Objective. Sterigmatocystin (STC) is a polyketyde mycotoxin similar to aflatoxin B1 (AFB1) but with a larger aromatic and hydrophobic surface. Thus, non-covalent interactions are likely to play a significant role in interactions of STC with biomacromolecules and its toxicity. Recently we have shown that, unlike AFB1, STC forms very stable aggregates in aqueous solutions, yielding a specific and strong signal in circular dichroism (ICD band at 350 nm). In this research, the pre- formed aggregate was used to study non-covalent interactions of STC with sugammadex, and other gama (γ–CD) and beta types of cyclodextrins (β- CD). Materials/Methods. To prepare a stable STC aggregate (10-6 M to 10-5 M), the stock solution of STC in organic solvent was added to aqueous buffer solution. For titration experiments the stock solutions of sugammadex, γ-CD, β-CD and HSA were prepared in the same aqueous solvents. Circular dichroism spectra (220–550 nm) were measured on the JASCO J-815 spectropolarimeter and fluorescent spectra (λexc 280 nm, λem 300–500 nm) on the Cary Eclipse fluorescence spectrophotometer (quartz cuvettes, l = 1 cm, 25 °C). All spectra were baseline-corrected and in consideration of the volume effect, analysed and visualised by Origin Lab 9.0. Microcalorimetric titrations were performed on a MicroCal PEAQ-ITC calorimeter (25 °C) and analysed in MicroCal PEAQ-ITC Analysis Software using the One Set Sites Fitting Model. Results. Our studies demonstrated that STC non- covalently interacts with various CDs, showing the highest binding affinity for sugammadex and γ–CD. Competitive fluorescence experiments, supported by isothermal titration calorimetry, demonstrated an efficient displacement of STC from HSA-STC complex by CDs. Conclusions. These results are a proof-of-concept that CDs can be used to complex STC. Similarly, as sugammadex extracts neuromuscular relaxant, e.g., rocuronium, from blood and blocks their bioactivity, it could also be used upon acute intoxication to encapsulate larger part of the STC mycotoxin from HSA.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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