Toxicity assessment of free and dendrimer-complexed curcumin in zebrafish larvae

Abstract

Background: Curcumin (CUR) is a natural polyphenol widely used as a colorant in food and as a bioactive compound in medicine.In vivo assays in murine models and humans confirmed that dietary CUR is extremely safe. However, three works reported that CUR exhibits lethal and teratogenic effects on zebrafish embryos. Also, CUR is insoluble and unstable in aqueous media, so it needs to be protected for its incorporation in food or medicine. Methods: The effects of free CUR and dendrimer-complexed CUR (CUR-DG4.0 and CUR-DG4.5) on the viability, the spontaneous movement, the heart rate, the morphological changes, and the hepatic-state of zebrafish larvae were deeply studied. Results: The CUR reduced the viability, caused malformations, and showed neurotoxic, cardiotoxic and hepatotoxic effects in sub-lethal concentrations. The CUR-DG4.0 complexes exacerbated the toxicity due to a synergism effect induced by cationic dendrimers and an increase in the uptake of CUR by larvae. The CUR-DG4.5 complexes reduced the toxics effects of CUR, without modified its uptake, showing an important hepatoprotective effect. Conclusions: This work showed for the first time that CUR present tissue-specific toxic effects in zebrafish larvae, and that CUR-treated zebrafish larvae could be used as a model for studying the hepatoprotective action of other drugs and nanomaterials.