| ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY. | |
| | |
MedLine Citation:
|
PMID: 22118289 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
ABSTRACT: Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia , aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. |
| | |
Authors:
|
Horacio A Priestap; Maria C Torres; Robert A Rieger; Kathleen Dickman; Tomoko Freshwater; David R Taft; Manuel Barbieri; Charles R Iden |
Related Documents
:
|
868439 - Compartmentation of the amino acid pool in saccharomycopsis lipolytica. 6789869 - Utilization of amino acid analogues in diets of young turkeys. 10565359 - Amino acids with anabolic properties. 17447789 - Mechanisms of alkylpyrazine formation in a potato model system containing added glycine. 1382229 - Effects of amino acids on sister-chromatid exchanges. 6135999 - Central respiratory and cardiovascular effects in the rat of some putative neurotransmi... 22058919 - Rac-cis-cyclo-hexane-1,2-dicarb-oxy-lic acid-isoquinoline (1/1). 19502729 - Glutamyl trna synthetases and glutamic acid induce sexual differentiation of schizosacc... 9453429 - Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites i... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-11-25 |
Journal Detail:
|
Title: Chemical research in toxicology Volume: - ISSN: 1520-5010 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
|
Created Date: 2011-11-28 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Different processes lead to similar patterns: a test of codivergence and the role of sea level and c...
Next Document: Lower Triassic stromatolites in Luodian County, Guizhou Province, South China: evidence for the prot...