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In vitro model for assessment of nephrotoxicity and nephroprotection of natural products

par Bunel, Valérian ;Antoine, Marie-Hélène ;Nortier, Joëlle ;Duez, Pierre ;Stévigny, Caroline
Référence 15th Forum of Pharmaceutical Sciences, Belgian Society of Pharmaceutical Sciences (12/05/2011: Spa, Belgium)
Publication Non publié, 2011-05-12

Communication à un colloque

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Résumé :

Introduction. Besides the myth of “natural and safe” remedies, the real innocuity of many herbal products is actually not clearly defined. Medicinal plants have become very popular in complementary and alternative medicine; they are now often used as preventive and/or therapeutic options by patients suffering from serious chronic diseases who are then exposed to possible adverse reactions. As an example, we may consider the "Aristolochia" case, which took place in Belgium during the '90s; 120 cases of interstitial fibrosis have been related to the ingestion of slimming pills containing aristolochic acids (AA), which caused damages to renal proximal tubular epithelial cells (RPTEC) and finally led to end-stage renal failure, requiring dialysis and transplantation. Commonly used drugs such as cisplatine (cisPt) or ciclosporine A (CsA) are also responsible for such adverse reactions. Efficient means to precociously detect and avoid such damages and/or to promote kidney regeneration remain to be developed. Aims: To build an in vitro tool able to rapidly detect early signs of nephrotoxicity, and in case of innocuity further investigate if selected herbal products have a protective effect against drug-induced nephrotoxicity. Methods. HK-2 cells, originating from human RPTEC, were exposed to AA (50 µM), cisPt (50 µM) or CsA (5 µM), or to a methanolic extract of ginseng (Panax ginseng C.A. Meyer) (5-50 µg/ml). Nephrotoxicity was evaluated by determining the loss of intracellular β-catenin and secretion of fibronectin in cells supernatants. Effects on proliferation were evaluated according to the ki-67 index and further investigated by cell cycle analysis. Results. As compared to controls, nephrotoxic compounds induced loss of β-catenin and fibronectin secretion. No similar effects were observed after cell exposure to a methanolic extract of ginseng, suggesting no harmful cytotoxicity in the present model. Instead, ki-67 expression and cell cycle analysis both supported a proliferative effect of ginseng. Conclusions. These preliminary results indicate this model enables (1) to detect early toxicity on HK-2 cells, and (2) to highlight an effect on cell proliferation. It therefore may be used to screen herbal extracts susceptible to be nephrotoxic or nephroprotector.