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

Cucurbit [7]uril (CB [7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP + (N-methyl-4-phenylpyridine). The CB [7]/neurotoxin host−guest complexes were studied in detail with 1 H NMR, electrospray ionization mass spectrometry, UV− visible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP + , respectively, by CB [7] in aqueous solutions with relatively strong affinities and 1:1 host− guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP + induced neurodegeneration (often referred to as a Parkinson's disease model) was observed to be strongly inhibited in vivo by the synthetic CB [7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.

A general anesthetic is a drug that brings about a reversible loss of consciousness, during a surgical or therapeutic procedure to render the patient free of pain and anxiety. However, the effect of anesthetics may linger far beyond the necessary time required and induce adverse effects. In addition, many surgical patients need to recover to a conscious state that allows them to make important decisions soon after their surgery. Unfortunately, there are currently no clinically-available anti-dotes to reverse the effects of anesthetics. In this study, we demonstrate the in vitro supramolecular host-guest complexations between macrocyclic cucurbit [7]uril (CB [7]) and a commonly used general anesthetic in fish, tricaine mesylate (TM), and we report for the first time the in vivo reversal effect of CB [7] to general anesthesia induced by TM with zebrafish models. These findings might lead to a new approach that may allow patients to regain lucidity much faster than their natural recovery from general anesthesia, and may also be used to reverse potentially life-threatening toxic effects encountered by some patients in response to general anesthesia.

Doxorubicin (Dox) is an anthracycline antibiotic widely used in clinics as an anticancer agent. However, the use of Dox is limited by its cardiotoxicity. We have previously shown that a Danshensu (DSS) derivative, ADTM, displayed strong cardioprotective effects. With improved chemical stability and activity, a novel DSS derivative, D006, based on the structure of ADTM, was synthesized. In the present study, the protective effects of D006, indexed by attenuation of the cardiotoxicity induced by Dox as well as chemosensitizing effects that increase the antitumor activity of Dox, were investigated. Our results showed that D006 was more potent than either parental compound, or their use in combination, in ameliorating Dox‐induced toxicity in H9c2 cells. In our zebrafish model, D006, but not DSS, alone significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, D006 upregulated mitochondrial biogenesis and increased mtDNA copy number after Dox treatment of H9c2 cells. D006 promoted the expression of HO‐1 protein in a time‐dependent manner while the HO‐1 inhibitor, Znpp, reversed the protective effects of D006. In human breast tumor MCF‐7 cells, D006 enhanced Dox‐induced cytotoxicity by increasing apoptosis. In conclusion, our results indicate that a new DSS derivative exhibits promising protective effects against Dox‐induced cardiotoxicity both in vivo and in vitro, an effect at least partially mediated by induction of HO‐1 expression and the activation of mitochondrial biogenesis. Meanwhile, D006 also potentiated the anti‐cancer effects of Dox in breast tumor cells. J. Cell. Biochem. 117: 94–105, 2016. © 2015 Wiley Periodicals, Inc.