Mayayo-Vallverdu 2023 Redox Biol

Mayayo-Vallverdú C, López de Heredia M, Prat E, González L, Espino Guarch M, Vilches C, Muñoz L, Asensi MA, Serra C, Llebaria A, Casado M, Artuch R, Garrabou G, Garcia-Roves PM, Pallardó FV, Nunes V (2023) The antioxidant l-Ergothioneine prevents cystine lithiasis in the Slc7a9^-/- mouse model of cystinuria. https://doi.org/10.1016/j.redox.2023.102801

» Redox Biol 64:102801. PMID: 37418888 Open Access

Mayayo-Vallverdu Clara, Lopez de Heredia Miguel, Prat Esther, Gonzalez Laura, Espino Guarch Meritxell, Vilches Clara, Munoz Lourdes, Asensi Miguel A, Serra Carmen, Llebaria Amadeu, Casado Mercedes, Artuch Rafael, Garrabou Gloria, Garcia-Roves Pablo M, Pallardo Federico V, Nunes Virginia (2023) Redox Biol

Abstract: The high recurrence rate of cystine lithiasis observed in cystinuria patients highlights the need for new therapeutic options to address this chronic disease. There is growing evidence of an antioxidant defect in cystinuria, which has led to test antioxidant molecules as new therapeutic approaches. In this study, the antioxidant l-Ergothioneine was evaluated, at two different doses, as a preventive and long-term treatment for cystinuria in the Slc7a9^-/- mouse model. l-Ergothioneine treatments decreased the rate of stone formation by more than 60% and delayed its onset in those mice that still developed calculi. Although there were no differences in metabolic parameters or urinary cystine concentration between control and treated mice, cystine solubility was increased by 50% in the urines of treated mice. We also demonstrate that l-Ergothioneine needs to be internalized by its transporter OCTN1 (Slc22a4) to be effective, as when administrated to the double mutant Slc7a9^-/-Slc22a4^-/- mouse model, no effect on the lithiasis phenotype was observed. In kidneys, we detected a decrease in GSH levels and an impairment of maximal mitochondrial respiratory capacity in cystinuric mice that l-Ergothioneine treatment was able to restore. Thus, l-Ergothioneine administration prevented cystine lithiasis in the Slc7a9^-/- mouse model by increasing urinary cystine solubility and recovered renal GSH metabolism and mitochondrial function. These results support the need for clinical trials to test l-Ergothioneine as a new treatment for cystinuria. • Keywords: Antioxidant, Cystine lithiasis, Cystinuria, Oxidative stress, Treatment, l-Ergothioneine • Bioblast editor: Plangger M • O2k-Network Lab: ES Barcelona Moren C, ES Barcelona Garcia-Roves PM

Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology Pathology: Other

Organism: Mouse Tissue;cell: Kidney Preparation: Permeabilized tissue

Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k

2023-07