Naslov
Competitive binding of aristolochic acid between various cyclodextrins and serum albumin as a model for acute poisoning detoxification

Autori
Gazdek, Nika ; Zonjić, Iva ; Nikšić-Franjić, Ivana ; Frkanec, Leo ; Piantanida, Ivo

Izvornik
Supramolecular chemistry (1061-0278) 33 (2022), 10; 569-577

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Aristolochic acid toxin ; cyclodextrins ; serum albumin ; ds-DNA ; competitive binding ; detoxification

Sažetak
We showed by UV/Vis, fluorescence and ITC experiments that aristolochic acid toxin (ARI) and its fluorescent analogue form inclusion complexes with various cyclodextrins (CDs), including the clinically used derivative of γ-CD: Sugammadex. The binding affinity of ARI toxin towards CDs varied on a CD size and rim modifications, whereby the stability of ARI toxin/Sugammadex complex was 2-fold greater than ARI toxin binding to serum albumin (BSA), blood protein well-known as a transporter of small molecules and similar to the ARI complex with ds-DNA. Molecular modelling studies supported the formation of ARI/ Sugammadex complex with carboxyl group of ARI exposed to water and ARI-condensed aromatic moiety deeply immersed into CD-cavity. These results are a proof-of-concept that CDs can be used to form a complex with ARI toxins ; similarly, as Sugammadex extracts neuromuscular relaxation agents (e.g. Rocuronium and Vecuronium) from blood to stop their bioactivity, it could be used as first aid upon acute intoxication to encapsulate larger part of the ARI toxin in competition with serum albumin or ds-DNA and significantly reduce ARI toxic absorption in the organism. The presented data strongly support further detailed study in vivo, which would address the excretion efficiency of CD- encapsulated aristolochic acid toxin from the organism.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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