Revealing a pre-neoplastic renal tubular lesion by p-S6 protein immunohistochemistry after rat exposure to aristolochic acid
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Aristolochic acid (AA) has, in the last decade, become widely promoted as the cause of the Balkan endemic nephropathy and associated renal or urothelial tumours, although without substantial focal evidence of the quantitative dietary exposure via bread in specific households in hyperendemic villages. Occasional ethnobotanical use of Aristolochia clematitis might be a source of AA, and Pliocene lignite contamination of well-water is also a putative health risk factor. The aim of this study was two-fold: to verify if extracts of A. clematitis and Pliocene, or AA by itself, could induce the development of renal or urothelial tumours, and to test the utility of the ribosomal protein p-S6 to identify preneoplastic transformation. Rats were given extracts of A. clematitis in drinking water or AA I, by gavage. After seven months, renal morphology was studied using conventional haematoxylin and eosin and immunohistochemistry for ribosomal p-S6 protein. Plant extracts (cumulative AA approximately 1.8 g/kg b.w.) were tolerated and caused no gross pathology or renal histopathological change, with only faint diffuse p-S6 protein (except in the papilla) as in controls. Cumulative AA I (150 mg/kg b.w. given over 3 days) was also tolerated for seven months by all recipients, without gross pathology or kidney tumours. However, p-S6 protein over-expression was consistent particularly within the renal papilla. In one case given AA I, intense p-S6 protein staining of a proximal tubule fragment crucially matched the pre-neoplastic histology in an adjacent kidney section. We briefly discuss these findings, which compound uncertainty concerning the cause of the renal or upper urinary tract tumours of the Balkan endemic nephropathy.
Date Issued
2015-09-08
Date Acceptance
2015-08-23
Citation
Journal of Kidney Cancer and VHL, 2015, 2 (4)
ISSN
2203-5826
Publisher
Codon Publications
Journal / Book Title
Journal of Kidney Cancer and VHL
Volume
2
Issue
4
Copyright Statement
© 2015 Alexandra Gruia, Patrycja Gazinska, Diana Herman, Valentin Ordodi, Calin Tatu, Peter George Mantle. This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)
Publication Status
Published
Date Publish Online
2015-09-07