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In vitro model assessing early nephrotoxicity of herbal products

par Bunel, Valérian ;Antoine, Marie-Hélène ;Nguyen, Ky TV.;Husson, Cécile ;Stévigny, Caroline ;Duez, Pierre ;Nortier, Joëlle
Référence Belgian Society of Nephrology annual meeting (03/03/2011: Brussels, Belgium)
Publication Non publié, 2011-03-03

Communication à un colloque

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Résumé :

Introduction. Medicinal plants are very popular in complementary and alternative medicine. Besides the myth of “natural and safe” remedies, the innocuity of compounds is actually not clearly defined. The so-called Chinese herb nephropathy is a well-known example in our country: >100 women developed interstitial fibrosis and tubular atrophy after intake of slimming pills containing aristolochic acids (AA), leading to end-stage kidney disease and a dramatic prevalence of urothelial carcinoma. Aims of the study. To design in vitro screening tools in order to rapidly detect early signs of tubulotoxicity, focusing on tubular dedifferentiation and apoptosis. Methods. Human Kidney HK-2 cells, originating from human renal proximal tubular epithelial cells were exposed during 72h to AA (50 µM) or to a crude methanolic extract of ginseng (Panax ginseng C.A. Meyer, Araliaceae) (5 and 50 µg/ml). Tubular dedifferentiation was evaluated by immunofluorescence microscopy of specific markers: β-catenin (a tight-junction protein common on epithelial cells) and vimentin (intermediate filament reflecting a mesenchymal phenotype). These markers were semi-quantified and compared to control cells. Fibronectin concentration was determined in the supernatants. Results. As compared to controls, AA treated cells exhibited marked nuclei fragmentation and a significant delocalization of β-catenin with overexpression of vimentin (P<0.001, mean of 6 experiments), suggesting a marked apoptosis and dedifferentiation, respectively. An increased fibronectin concentration was also detected in the supernatants. No similar effects were observed after cell exposure to a crude methanolic extract of ginseng, suggesting no harmful cytotoxicity in the present model. Conclusions. According to these preliminary results, rapid and non invasive in vitro tests investigating early dedifferentiation of HK-2 cells may be useful in order to screen herbal extracts susceptible to induce renal tubulotoxicity.