| Cyclosporine A-induced toxicity in two renal cell culture models (LLC-PK1 and MDCK). | |
| | |
MedLine Citation:
|
PMID: 12365797 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Renal damage caused by therapeutic treatment with cyclosporine A has been well documented. Clinical experiences have shown that cyclosporine A nephrotoxicity is determined by interstitial fibrosis with tubular atrophy. However, the exact mechanism by which this drug causes nephrotoxicity has not yet been clarified. This study used an in vitro model in an attempt to identify the cellular mechanisms underlying kidney cyclosporine A damage. We used two cell lines with the characteristics of proximal and distal tubule cells (pig kidney proximal tubular epithelial cell line [LLC-PK1] and Madin-Darby canine kidney cell line [MDCK]. The cell lines were treated with cyclosporine A for 24 h. After the treatment, the cells were stained with Trypan Blue to estimate cell viability and processed by histochemical reactions to evaluate their cellular metabolism. Four enzymes (acid phosphatase, alkaline phosphatase, lactate dehydrogenase and succinate dehydrogenase) were considered. The cell viability assay showed that the LLC-PK1 cell line was more sensitive to cyclosporine A than MDCK. Remarkably, the LLC-PK1 cells disappeared with cyclosporine A treatment. As for the hydrolytic enzymes, only acid phosphatases showed an increased positivity in the treated LLC-PK1 cells. Similarly, lactate dehydrogenase showed a different activity histochemically. No statistically significant alterations were observed in the succinate dehydrogenase reaction. The cyclosporine A-treated MDCK cell lines did not show any difference in either their hydrolytic or succinate dehydrogenase enzyme positivity with respect to the control line. In contrast, there was a significant increase in lactate dehydrogenase activity. This study allowed the possible mechanism of cyclosporine A-induced damage in renal tubular cells to be evaluated. The enzymatic changes happened rapidly (during the 24 h of treatment), suggesting that this alteration was one of the steps by which cyclosporine A induced toxicity. Moreover, since acid phosphatase is a marker of protein catabolism, the variation in the activity of this enzyme, in the LLC-PK1 line only, showed that cyclosporine can induce alterations leading to cellular toxicity. The modifications in lactate dehydrogenase activity, in both lines, suggested that this drug caused cell stress, inducing the production of lactic acid from glucose in the presence of oxygen. In conclusion, cyclosporine A treatment may force LLC-PK1 and MDCK cells to use anaerobic glycolysis preferentially. Further, these enzyme alterations may represent an epiphenomenon or a consequence of cyclosporine A toxicity. |
| | |
Authors:
|
Rita Rezzani; Paola Angoscini; Elisa Borsani; Luigi Rodella; Rossella Bianchi |
Related Documents
:
|
1677057 - P-glycoprotein expression and in vitro reversion of doxorubicin resistance by verapamil... 2358437 - Analysis of glycoprotein-bound carbohydrates from pluripotent embryonal carcinoma cells... 8827047 - Functional study of multidrug resistance with fluorescent dyes. limits of the assay for... 19264847 - Enhancement of doxorubicin cytotoxicity on human esophageal squamous cell carcinoma cel... 51687 - A comparison of aldehyde fuchsin and alcian blue staining of neurosecretory material in... 10900467 - Cell-cycle arrest at g2/m and growth inhibition by apigenin in human colon carcinoma ce... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Histochemical journal Volume: 34 ISSN: 0018-2214 ISO Abbreviation: Histochem. J. Publication Date: 2002 Jan-Feb |
Date Detail:
|
Created Date: 2002-10-07 Completed Date: 2003-04-02 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0163161 Medline TA: Histochem J Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 27-33 Citation Subset: IM |
Affiliation:
|
Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acid Phosphatase
/
analysis,
metabolism Alkaline Phosphatase / analysis, metabolism Animals Cell Line Cell Survival / drug effects Cyclosporine / toxicity* Dogs Immunohistochemistry Immunosuppressive Agents / toxicity* Kidney Tubules / cytology, drug effects*, enzymology L-Lactate Dehydrogenase / analysis, metabolism LLC-PK1 Cells Succinate Dehydrogenase / analysis, metabolism Swine Trypan Blue / chemistry |
| Chemical | |
Reg. No./Substance:
|
0/Immunosuppressive Agents; 59865-13-3/Cyclosporine; 72-57-1/Trypan Blue; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.3.99.1/Succinate Dehydrogenase; EC 3.1.3.1/Alkaline Phosphatase; EC 3.1.3.2/Acid Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Different patterns of expression of five neuropeptides in the adrenal gland and kidney of two specie...
Next Document: Analysis of vitamin D-receptor (VDR) and retinoid X-receptor alpha in breast cancer.