Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells.

Abstract

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.

• Authors: Marie-Hélène Antoine, Cécile Husson, Tatiana Yankep, Souhaila Mahria, Vanessa Tagliatti, Jean-Marie Colet, Joëlle Nortier
• Journal: Toxins (Toxins (Basel)) Vol. 14 Issue 2 (02 10 2022) ISSN: 2072-6651 [Electronic] Switzerland
• PMID: 35202159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Aristolochic Acids
• Protective Agents
• Nebivolol

Topics

• Antioxidants (pharmacology)
• Aristolochic Acids (toxicity)
• Cells, Cultured (drug effects)
• Endothelial Cells (drug effects)
• Humans
• Nebivolol (pharmacology)
• Nephrotic Syndrome (chemically induced, prevention & control)
• Oxidative Stress (drug effects)
• Protective Agents (pharmacology)