J Journal of Applied Toxicology publishes reviews and research articles on mechanistic, fundamental and applied research relating y to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all routes of exposure) and in vitro/ex vivo. Focus is on toxicogenomics and proteomics, teratogenesis/developmental/reproductive toxicology, carcinogenesis, mutagenesis,pharmacokinetics, pharmacotoxicological and metabolic mechanisms, risk assessment, environmental toxicology and environmental health as applied to humans (including epidemiological studies). In addition Journal of Applied Toxicology also publishes analytical and method development studies, mechanistic and molecular y toxicology studies on novel or existing drugs and chemicals, addressing important or topical aspects of toxicology. Special emphasis is given to papers of clear relevance to human health and regulatory pharmaceutical/chemical toxicology.
-The utility of HepaRG cells as an in vitro cell-based assay system for predicting druginduced phospholipidosis (PLD) was investigated. In experiment 1, 10 PLD-positive compounds and 11 PLD-negative compounds were selected. HepaRG cells were treated with each compound for 48 hr. In experiment 2, loratadine and desloratadine, a major metabolite of loratadine, were used to assess metabolic activation for PLD. HepaRG cells were treated with loratadine and desloratadine in the presence or absence of 500 μM 1-aminobenzotriazole (ABT), a broad CYP inhibitor, for 48 hr. After treatment with compounds in experiments 1 and 2, the relative fluorescence intensity (RFI) was measured using LYSO-ID Red dye to assess the PLD induction. In experiment 1, our cell-based assay system using HepaRG cells exhibited 100% sensitivity and 100% specificity for predicting drug-induced PLD. In experiment 2, loratadine increased the RFI in the PLD assay. However, the increase in the RFI was not observed in co-treatment with loratadine and ABT. In addition, desloratadine increased the RFI in the presence and absence of ABT. These results suggested that metabolic activation of loratadine may contribute to PLD in HepaRG cells. We newly demonstrated that HepaRG cells have a high ability for predicting drug-induced PLD. In addition, we newly showed that HepaRG cells may predict drug-induced PLD mediated by metabolic activation of loratadine. Thus, a cell-based assay system using HepaRG cells is a useful model for predicting drug-induced PLD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.