Document Detail


In vitro cytotoxicity assay with selected chemicals using human cells to predict target-organ toxicity of liver and kidney.
MedLine Citation:
PMID:  17376646     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In order to elucidate the feasibility of predicting liver and kidney target-organ toxicity using in vitro cytotoxicity assay, cytotoxicity of selected chemicals, acetaminophen (AAP), mitomycin (MMC), cupric chloride (CuCl2), phenacetin, cadmium chloride (CdCl2) and aristolochic acid (AA), was studied using human hepatoma (Bel-7402) cells and human renal tubular epithelial (HK-2) cells. Cell viability and mitochondrial permeability transition (MPT) were assessed by the neutral red (NR) assay and laser scanning confocal microscope, respectively. The results of the NR assay indicated that cytotoxicity of hepatoxicants, AAP, MMC and CuCl2 in liver cells was higher than that in kidney cells. Cytotoxicitiy of nephrotoxicant, CdCl2 was lower in liver cells than that in kidney cells, but nephrotoxicant phenacetin and AA was higher cytotoxicity in liver cells than that in kidney cells. The cytotoxicity of AAP and phenacetin was strengthened in the presence of S9 mixture, indicating that they are metabolism-mediated cytotoxicants. All selected chemicals disrupted MPT in dose-dependent manner. Linear regression analysis revealed a good correlation between the IC50 values of cytotoxicity and the EC50 values of MPT in Bel-7402 cells and HK-2 cells (R2 = 0.987 and 0.823, respectively). Cytotoxicity assay in vitro using specific cells show good compatibility with target-organ toxicity in vivo. However, limitations of in vitro cytotoxicity assay are due to its incomplete process of ADME and the defect of predicting chronic toxicity effect after long-term exposure to a chemical.
Authors:
Lijuan Zhang; Xiaoqun Mu; Juanling Fu; Zongcan Zhou
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-20
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  21     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-04-13     Completed Date:  2007-08-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  734-40     Citation Subset:  IM    
Affiliation:
School of Public Health, Peking University, Beijing, 100083, PR China.
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MeSH Terms
Descriptor/Qualifier:
Acetaminophen / toxicity
Aristolochic Acids / toxicity
Cadmium Chloride / toxicity
Cell Line
Cell Survival / drug effects
Copper / toxicity
Drug-Induced Liver Injury / pathology*
Humans
Kidney Diseases / chemically induced*,  pathology*
Mitochondria / drug effects,  ultrastructure
Phenacetin / toxicity
Regression Analysis
Subcellular Fractions / drug effects
Chemical
Reg. No./Substance:
0/Aristolochic Acids; 10108-64-2/Cadmium Chloride; 103-90-2/Acetaminophen; 313-67-7/aristolochic acid I; 62-44-2/Phenacetin; 7440-50-8/Copper; 7447-39-4/cupric chloride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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