| Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation. | |
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MedLine Citation:
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PMID: 14705839 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Occupational exposure to solvents may be associated with development and progression of tubulo-interstitial fibrosis and chronic renal failure. However, the cellular mechanisms by which this occurs remain elusive. MATERIALS AND METHODS: The cytotoxicity of proximal tubular cells (LLC-PK1) exposed to 106 mg/mL of p-xylene or 92 mg/mL of toluene was compared with untreated controls using cell viability (MTS assay) and caspase-3 activity, with or without caspase-3 selective inhibitor. RESULTS: Both compounds reduced cell viability and increased caspase-3 activation (P < 0.005). Inhibition of caspase-3 by the selective inhibitor DEVD-CHO prevented injury (P < 0.001) and inhibited solvent-induced caspase-3 activation (P < 0.005). CONCLUSION: Inhibition of caspase-3, the critical caspase in the apoptosis process, prevents cell injury in LLC-PK1. This suggests that caspase-3 may play a pivotal role in solvent-induced proximal tubular cell injury. |
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Authors:
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Saeed S Al-Ghamdi; Martin J Raftery; Muhammad M Yaqoob |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of toxicology. Clinical toxicology Volume: 41 ISSN: 0731-3810 ISO Abbreviation: J. Toxicol. Clin. Toxicol. Publication Date: 2003 |
Date Detail:
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Created Date: 2004-01-06 Completed Date: 2004-01-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8213460 Medline TA: J Toxicol Clin Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 941-5 Citation Subset: AIM; IM |
Affiliation:
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Department of Experimental Medicine and Nephrology, St. Bart's and Royal London School of Medicine and Dentistry, Queen Mary-University of London, London, UK. s_alghamdi@go.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Caspase 3 Caspases / antagonists & inhibitors, metabolism* Cell Line Cell Survival / drug effects Cysteine Proteinase Inhibitors / pharmacology Enzyme Activation Kidney Tubules, Proximal / cytology, drug effects*, enzymology Oligopeptides / pharmacology Solvents / toxicity* Swine Toluene / toxicity* Xylenes / toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Cysteine Proteinase Inhibitors; 0/Oligopeptides; 0/Solvents; 0/Xylenes; 0/aspartyl-glutamyl-valyl-aspartal; 106-42-3/4-xylene; 108-88-3/Toluene; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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