Developmental and organ-specific toxicity of cucurbit[7]uril: in vivo study on zebrafish models

Abstract

The macrocyclic molecular container cucurbit [7]uril (CB[7]), the most water-soluble homologue in the cucurbit[n]uril family (n = 5-8, 10, 14), has been evaluated for its in vivo toxicity profile, including its developmental toxicity such as its effect on hatching, growth and survival, as well as its potential organ-specific toxicities such as cardiotoxicity, hepatotoxicity, and locomotion and behavioral toxicity, using zebrafish models. The results revealed that CB[7] has measureable cardiotoxicity and locomotion and behavioral toxicity at concentrations of ~500 µM or higher, and negligible developmental and hepatotoxicity at concentrations up to 750 µM, although extended exposure to CB[7] at the 500-750 µM concentration range induced the mortality of tested fish. These results demonstrate for the first time with live in vivo animal models that

Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor

“…8−10 For over a decade, we have been actively investigating the host−guest chemistry 11−17 and biocompatibility 18 of CB [7]. Recently, CB[n] (especially CB [7]) and derivatives have been demonstrated to reverse or inhibit the biological activities of a group of guest molecules due to strong host−guest complexations.…”

Molecular Encapsulation of Histamine H2-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study

“…On the one hand, CB [7]'s safety profile and biocompatibility has been well studied with several in vitro, in vivo and ex vivo models [5][6][7]. For instance, several in vitro studies on cell cultures have shown that CB [7] exhibits very low toxicity at up to 1 mM concentrations.…”

“…The effects observed for an intravenous single dose i.v. injection with a mouse model demonstrated that CB [7] has a very low acute toxicity at a dose of 250 mg/kg, based on a body weight change of less than 10% within 5 days of the injections [5]. The tissue specific toxicity including neuro-, myo-and cardiotoxicity of CB [7] has been examined with the use of ex vivo electrophysiological models.…”

“…CB[n]s consist of n glycoluril units that are connected by n pairs of methylene groups, with a lipophilic cavity in the middle that is accessible by a variety of guest molecules via two polar carbonyl-laced portals [3,4]. Due to its superior water-solubility, CB [7] (Figure 1) is a particularly attractive capsule to host a variety of guest molecules of biomedical and medical interest, both in vitro and in vivo [1,2].…”

“…For instance, several in vitro studies on cell cultures have shown that CB [7] exhibits very low toxicity at up to 1 mM concentrations. The effects observed for an intravenous single dose i.v.…”