Document Detail

Effects of therapeutic agents on cellular respiration as an indication of metabolic activity.
MedLine Citation:
PMID:  16634332     Owner:  NLM     Status:  MEDLINE    
Animal experiments are indispensable in the investigation of the toxicity of drugs on cells, but may not be preferred for ethical reasons and sensitivity. As an alternative procedure, we investigated the susceptibility of cells to drugs using the effect on cellular respiration as an indicator of cell activity (toxicity). The primary cultures (cell lines) used in this study included human fetal myocardial cells, skeletal muscle cells, nerve cells, hypophyseal cells, epithelial cells of gastric mucosa, lymphocytes, hepatocytes, pancreatic (exocrine) cells, renal tubular epithelial cells and fetal adrenal cortex cells, which were obtained from the American Type Culture Collection (ATCC). The drugs used were diazepam, haloperidol and levomepromazine maleate (psychoactive drugs), cisplatin and doxorubicin hydrochloride (anticancer agents). The cells were used at a density of 2 x 10(6) cells/2 mL of growth medium and, to test the susceptibility, each drug was prepared at a concentration of 10 g/mL. Experiment results indicated that, even with the same drug, sensitivity was markedly different depending on the cell lines. Cardiac muscle cells showed the strongest respiratory inhibition by Serenace and were least inhibited by Hirnamin. The highest sensitivity to Cercine was noted for neurons, while gastric mucosa cells had almost no sensitivity. Sensitivity to Serenace, which was expected to have a strong nerve action, was higher in myocardial cells instead. In the present study, we suggested the possibility of studying individual differences in drug sensitivity through investigation of toxicity in each organ as opposed to toxicity in the individual. In addition, Serenace, which was developed as a neurotopic agent, showed a higher toxicity in cardiac muscle cells than in neurons. This finding appeared noteworthy, not only for forensic toxicology, but also for clinical practice and drug development.
T Ishikawa; B L Zhu; H Maeda
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Human & experimental toxicology     Volume:  25     ISSN:  0960-3271     ISO Abbreviation:  Hum Exp Toxicol     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-04-25     Completed Date:  2006-05-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9004560     Medline TA:  Hum Exp Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  135-40     Citation Subset:  IM    
Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
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MeSH Terms
Cell Count
Cell Line
Cell Survival / drug effects
Diazepam / pharmacology
Hypnotics and Sedatives / pharmacology
Metabolism / drug effects*
Microscopy, Electron
Mitochondria / drug effects,  metabolism
Oxygen / analysis
Oxygen Consumption / drug effects*
Reg. No./Substance:
0/Hypnotics and Sedatives; 439-14-5/Diazepam; 7782-44-7/Oxygen

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

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