Revealing a pre-neoplastic renal tubular lesion by p-S6 protein immunohistochemistry after rat exposure to aristolochic acid
| Autor: | Calin A. Tatu, Diana Herman, Patrycja Gazinska, Alexandra T. Gruia, Valentin Ordodi, Peter George Mantle |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Aristolochic acid lcsh:RC870-923 lcsh:RC254-282 Gross examination chemistry.chemical_compound Balkan nephropathy medicine Kidney biology Ribosomal phospho-S6 protein Aristolochia clematitis Ochratoxin A Histology lcsh:Diseases of the genitourinary system. Urology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens biology.organism_classification Urothelial tumours Major duodenal papilla medicine.anatomical_structure chemistry Renal papilla Original Article Balkan Nephropathy |
| Zdroj: | Journal of Kidney Cancer and VHL Journal of Kidney Cancer and VHL, Vol 2, Iss 4, Pp 153-162 (2015) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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