Gene Expression Profiles Distinguish the Carcinogenic Effects of Aristolochic Acid in Target (Kidney) and Non-target (Liver) Tissues in Rats

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Aristolochic acid (AA) is the active component of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. AA, however, induced nephropathy and urothelial cancer in people and malignant tumors in the kidney and urinary tract of rodents. Although AA is bioactivated in both kidney and liver, it only induces tumors in kidney. To evaluate whether microarray analysis can be used for distinguishing the tissue-specific carcinogenicity of AA, we examined gene expression profiles in kidney and liver of rats treated with carcinogenic doses of AA.

Results

Microarray analysis was performed using the Rat Genome Survey Microarray and data analysis was carried out within ArrayTrack software. Principal components analysis and hierarchical cluster analysis of the expression profiles showed that samples were grouped together according to the tissues and treatments. The gene expression profiles were significantly altered by AA treatment in both kidney and liver ( p < 0.01; fold change > 1.5). Functional analysis with Ingenuity Pathways Analysis showed that there were many more significantly altered genes involved in cancer-related pathways in kidney than in liver. Also, analysis with Gene Ontology for Functional Analysis (GOFFA) software indicated that the biological processes related to defense response, apoptosis and immune response were significantly altered by AA exposure in kidney, but not in liver.

Conclusion

Our results suggest that microarray analysis is a useful tool for detecting AA exposure; that analysis of the gene expression profiles can define the differential responses to toxicity and carcinogenicity of AA from kidney and liver; and that significant alteration of genes associated with defense response, apoptosis and immune response in kidney, but not in liver, may be responsible for the tissue-specific toxicity and carcinogenicity of AA.

Related collections

Most cited references 38

Record: found
Abstract: found
Article: found

Is Open Access

In silico prediction of protein-protein interactions in human macrophages

Oussema Souiai, Fatma Zahra Guerfali, Slimane Miled … (2015)

Background: Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results: We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion: Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.

0 comments Cited 1278 times – based on 0 reviews

Preprint

     Review now

Bookmark

Record: found
Abstract: found
Article: not found

Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)

J Nortier, M. Martinez, H. Schmeiser … (2000)

Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.

0 comments Cited 186 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs.

R Vanhaelen-Fastre, M Jadoul, C Richard Boland … (1993)

Two similar cases of rapidly progressive fibrosing interstitial nephritis in young women who followed the same slimming regimen prompted us to conduct an epidemiological survey of the nephrology centres of Brussels and to further investigate the exact nature of this slimming treatment. Seven other women under the age of 50 in terminal or preterminal renal failure were admitted for dialysis in 1991 and 1992. They had all followed a slimming regimen in the same medical clinic. Renal biopsy samples in eight of the nine cases showed extensive interstitial fibrosis without glomerular lesions. Two of the patients were seen for the first time in terminal renal failure and were started immediately on dialysis. For the seven other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within about 3 months. The clinic had specialised in slimming treatments for the previous 15 years without any problems. In May, 1990, therapy was changed, with the introduction of two Chinese herbs (Stephania tetrandra and Magnolia officinalis). In June, 1992, three of twenty-five randomly selected women who had followed the same regimen during at least 3 months from 1990 had impaired renal function. Chemical analysis of some brands of these Chinese herbs did not show nephrotoxic contaminants of fungal or plant origin (ochratoxin or aristolochic acid) or adulteration by diuretics or antiinflammatory drugs. However, the medicinal preparation of the capsules taken by patients had different alkaloid profiles from those expected in Chinese plants. The striking relation between a specific type of fibrosing interstitial nephritis in young women and a slimming treatment involving Chinese herbs adds support to the arguments against uncontrolled therapy with herbal preparations.

0 comments Cited 130 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Conference

Journal ID (nlm-ta): BMC Bioinformatics

Title: BMC Bioinformatics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2105

Publication date Collection: 2006

Publication date (Electronic): 26 September 2006

Volume: 7

Issue: Suppl 2

Page: S20

Affiliations

[1 ]Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, US FDA, Jefferson, AR 72079, USA

[2 ]Division of Systems Toxicology, National Center for Toxicological Research, US FDA, Jefferson, AR 72079, USA

[3 ]Molecular Biology SDS/Arrays Group, Applied BioSystems, Foster City, CA 94404, USA

[4 ]Z-Tech Corporation, 3900 NCTR Road, Jefferson, Arkansas 72079 USA

[5 ]Solexa, Inc., 25861 Industrial Boulevard Hayward, CA 94545, USA

Article

Publisher ID: 1471-2105-7-S2-S20

DOI: 10.1186/1471-2105-7-S2-S20

PMC ID: 1683578

PubMed ID: 17118142

SO-VID: 57343fde-ced8-4cab-a2d8-afff44ee3c5e

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conference name: Third Annual MidSouth Computational Biology and Bioinformatics Society (MCBIOS) Conference. Bioinformatics: A Calculated Discovery

Gene Expression Profiles Distinguish the Carcinogenic Effects of Aristolochic Acid in Target (Kidney) and Non-target (Liver) Tissues in Rats

Read this article at

Abstract

Background

Results

Conclusion

Related collections

Genetoberfest

Most cited references 38

In silico prediction of protein-protein interactions in human macrophages

Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)

Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs.

Author and article information

Conference

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 119

Cited by 14

Most referenced authors 947