BERBERINE, A NATURAL ALKALOID, AFFECTS ZEBRAFISH CARDIOVASCULAR DEVELOPMENT

The zebrafish larva is increasingly used as a vertebrate animal model for in vivo drug discovery and for toxicology and biosafety assessments, bridging the gap between cell assays and rodent assays. In fact, zebrafish responses to toxic compounds are highly predictive of mammalian responses because of their very similar physiology, development and molecular pathways. In this study we aim at testing the potential toxicity and teratogenity of berberine, a natural alkaloid displaying a variety of therapeutical properties, whose effects on embryo development have been poorly characterized. We determined the LC50 value as 213 mg/L ± 8,30 and 156 mg/L ± 4,965 after 72 hrs and 96 hrs of treatment, respectively. We then analysed the effects observed at a concentration of 100 mg/L. In particular, we focused on cardiovascular development, which we found to be affected in a concentration and time dependent manner by berberine treatment. Treated embryos display cardiac defects, with a critical treatment window from 48hpf to 72hpf. Morphological analysis performed with heart specific markers shows the presence of defects in cardiac looping, while valves morphogenesis does not appear to be perturbed. We are currently further analyzing the cardiac defects as well as evaluating vascular alterations in pigmentless zebrafish larvae specifically expressing GFP in endothelial cells (casper/kdrl:GFP).