Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells
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 cultu...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/14/2/132 |
| _version_ | 1797476266624942080 |
|---|---|
| author | Marie-Hélène Antoine Cécile Husson Tatiana Yankep Souhaila Mahria Vanessa Tagliatti Jean-Marie Colet Joëlle Nortier |
| author_facet | Marie-Hélène Antoine Cécile Husson Tatiana Yankep Souhaila Mahria Vanessa Tagliatti Jean-Marie Colet Joëlle Nortier |
| author_sort | Marie-Hélène Antoine |
| collection | DOAJ |
| description | 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 <sup>1</sup>H-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. |
| first_indexed | 2024-03-09T20:55:32Z |
| format | Article |
| id | doaj.art-7b79dd2c9b0341c4872ab2ece546c52a |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T20:55:32Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-7b79dd2c9b0341c4872ab2ece546c52a2023-11-23T22:21:53ZengMDPI AGToxins2072-66512022-02-0114213210.3390/toxins14020132Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial CellsMarie-Hélène Antoine0Cécile Husson1Tatiana Yankep2Souhaila Mahria3Vanessa Tagliatti4Jean-Marie Colet5Joëlle Nortier6Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, BelgiumLaboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, BelgiumLaboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, BelgiumLaboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, BelgiumLaboratory of Human Toxicology, University of Mons (UMONS), 6 Avenue du Champ de Mars, B-7000 Mons, BelgiumLaboratory of Human Toxicology, University of Mons (UMONS), 6 Avenue du Champ de Mars, B-7000 Mons, BelgiumLaboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, Erasme Campus, 808 Route de Lennik, B-1070 Brussels, BelgiumAristolochic 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 <sup>1</sup>H-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.https://www.mdpi.com/2072-6651/14/2/132aristolochic acidsnebivololendothelial celloxidative stressmetabolomic |
| spellingShingle | Marie-Hélène Antoine Cécile Husson Tatiana Yankep Souhaila Mahria Vanessa Tagliatti Jean-Marie Colet Joëlle Nortier Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells Toxins aristolochic acids nebivolol endothelial cell oxidative stress metabolomic |
| title | Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells |
| title_full | Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells |
| title_fullStr | Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells |
| title_full_unstemmed | Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells |
| title_short | Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells |
| title_sort | protective effect of nebivolol against oxidative stress induced by aristolochic acids in endothelial cells |
| topic | aristolochic acids nebivolol endothelial cell oxidative stress metabolomic |
| url | https://www.mdpi.com/2072-6651/14/2/132 |
| work_keys_str_mv | AT marieheleneantoine protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells AT cecilehusson protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells AT tatianayankep protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells AT souhailamahria protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells AT vanessatagliatti protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells AT jeanmariecolet protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells AT joellenortier protectiveeffectofnebivololagainstoxidativestressinducedbyaristolochicacidsinendothelialcells |