[en] Aristolochic acids (AAs) are powerful nephrotoxins that cause severe tubulointerstitial fibrosis. The biopsy-proven peritubular capillary rarefaction may worsen the progression of renal lesions via tissue hypoxia. As we previously observed the overproduction of reactive oxygen species (ROS) by cultured endothelial cells exposed to AA, we here investigated in vitro AA-induced metabolic changes by 1H-NMR spectroscopy on intracellular medium and cell extracts. We also tested the effects of nebivolol (NEB), a β-blocker agent exhibiting antioxidant properties. After 24 h of AA exposure, significantly reduced cell viability and intracellular ROS overproduction were observed in EAhy926 cells; both effects were counteracted by NEB pretreatment. After 48 h of exposure to AA, the most prominent metabolite changes were significant decreases in arginine, glutamate, glutamine and glutathione levels, along with a significant increase in the aspartate, glycerophosphocholine and UDP-N-acetylglucosamine contents. NEB pretreatment slightly inhibited the changes in glutathione and glycerophosphocholine. In the supernatants from exposed cells, a decrease in lactate and glutamate levels, together with an increase in glucose concentration, was found. The AA-induced reduction in glutamate was significantly inhibited by NEB. These findings confirm the involvement of oxidative stress in AA toxicity for endothelial cells and the potential benefit of NEB in preventing endothelial injury.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Antoine, Marie-Hélène ; Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, Belgium
Husson, Cécile; Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, Belgium
Yankep, Tatiana; Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, Belgium
Mahria, Souhaila; Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, Belgium
TAGLIATTI, Vanessa ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Biologie humaine et Toxicologie
Colet, Jean-Marie ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Biologie humaine et Toxicologie
Nortier, Joëlle; Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, Belgium
Language :
English
Title :
Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells.
R550 - Institut des Sciences et Technologies de la Santé
Funders :
Association de Défense des Insuffisants Rénaux” (ADIR, Brussels, Belgium) and European Regional Development Fund and the Walloon Region, Belgium.
Funding text :
Funding: This work was partially supported by a grant from the “Association de Défense des Insuffisants Rénaux” (ADIR, Brussels, Belgium). The bioprofiling platform including the 1H-NMR 600 MHz Bruker spectrometer was supported by the European Regional Development Fund and the Walloon Region, Belgium.
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