Communication à un colloque
Résumé : Introduction. Renal proximal tubular epithelial cells (RPTEC) are often the preferential target of various nephrotoxic compounds. RPTEC apoptosis is frequently observed, leading to the partial loss of tubular function. Defects in the regeneration process of the injured RPTEC can trigger the onset of severe atrophy along with interstitial fibrosis which progressively results in chronic kidney disease. The "Aristolochia" case, which took place in Belgium during the '90s illustrates this pathophysiology. More than 120 cases of interstitial fibrosis have been related to the ingestion of slimming pills containing tubulotoxic aristolochic acids (AA) leading to end-stage renal failure. Aims. In this in vitro study, we attempted to identify compounds that would be likely to prevent AA-induced tubulotoxicity. Methods. HK-2 cells, originating from human RPTEC, were exposed to AA (50 µM), and/or to a methanolic extract of Panax ginseng C.A. Meyer (PG; 5 or 50 µg/ml). Nephrotoxicity and regeneration capacity were evaluated by investigating the following parameters: cellular viability (resazurin reduction) and apoptosis (annexin-V/PI staining), cell cycle analysis (flow cytometry), Ki-67 proliferation index and β-catenin expression (immunofluorescence stainings). Results. AA decreased overall cell viability [77.2 % vs. ctrl] due to induced apoptosis [177.5 % vs. ctrl]. Upon simultaneous treatment with 50 µg/ml PG, cells exhibited enhanced apoptosis [214.6 % vs. ctrl] and death [62.3 % vs. ctrl]. On the contrary, both doses of PG were able to increase cell proliferation [Ki-67 index of 128.6 and 204.1 % vs. ctrl for 5 and 50 µg/ml PG respectively] and β-catenin expression. Conclusions. These results indicate that Panax ginseng may enhance the effects of AA cytotoxicity. However, some benefits in tubules regeneration could be obtained with Panax ginseng. Further studies are needed to confirm these preliminary data.