3-(3,4-Dihydroxyphenyl)-7,8-dihydroxycoumarin is a newly synthesized coumarin derivative with a potent antioxidant effect. The aim of the present study is to investigate the safety of this compound, determining the in vitro cytotoxic and genotoxic in human peripheral blood mononuclear cells (PBMC) and in HepG2/C3A cells. Cell viability has been investigated by the trypan blue staining test and MTT assay and the genotoxicity by the comet assay and micronucleus test, using concentrations between 0.01 and 10 μg/ml. The compound proved to be noncytotoxic in both cell lines, at all tested concentrations, protecting the cells from the DNA damage. In addition, this molecule does not show clastogenic/aneugenic effects when performing the micronucleus test with cytokinesis blockade. Based on the obtained data, and the conditions of the experiments, we can conclude that the 3-(3,4-dihydroxyphenyl)-7,8-dihydroxycoumarin is a safe molecule up to a concentration of 10 μg/ml, which encourages further studies aiming to explore its potential as a drug candidate.
(1) Background: Drug-induced liver injury is a prevalent global health concern that necessitates urgent development of safe and effective treatment options for patients. Drug-carrying nanoparticles have garnered significant attention for dis-ease treatments due to their capacity to enhance drug solubility, provide drug protection, and prolong release duration, thereby improving drug bioavailability and increasing therapeutic efficacy. We initially present a nanostructured carrier incorporating glycyrrhetinic acid and transferrin.
The rising use of new chemicals and consumer products has spurred concerns about their potential to cause DNA damage and significant health issues, leading to a demand for genotoxicity testing data.
Traditional testing methods involve using laboratory animals, which are expensive and raise ethical issues, prompting the development of more accurate in vitro approaches that minimize animal use.
In particular, 3D cell models have emerged as promising alternatives to 2D cultures, providing better physiological relevance and predictive data for in vivo conditions, and their use in genotoxicity testing has been increasing, as highlighted in a review of 31 recent studies.
We describe a novel device to mimic the metastasis of cancer cells from the colon into the liver in a human model. The colon mimic is connected to the liver model by a gravity-driven recirculating unidirectional flow of a blood surrogate and can mimic the five steps of the metastatic cascade: invasion in the colon, intravasation into the bloodstream, systemic transportation, extravasation into the liver, and colonization in the liver. The colon mimic uses established normal colon epithelial organoid cells (NL) and human umbilical vein endothelial cells (HUVEC) plated on opposite sides of a membrane.
HEV infection has become a global health concern. The study of HEV pathogenicity has been hindered by the lack of a suitable in vitro culture system. In the present research, we systematic demonstration of efficient replication of swine GT4 HEV in A549 cells, Huh-7 cells, and HepG2/C3A cell lines.
Center for Human and Environmental Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States. Electronic address:
Physiologically relevant in vitro models are a priority in predictive toxicology to replace and/or reduce animal experiments. The compromised toxicant metabolism of many immortalized human liver cell lines grown as monolayers as compared to in vivo metabolism limits their physiological relevance. However, recent efforts to culture liver cells in a 3D environment, such as spheroids, to better mimic the in vivo conditions, may enhance the toxicant metabolism of human liver cell lines.
