The antioxidant L-Ergothioneine prevents cystine lithiasis in the Slc7a9-/- mouse model of cystinuria
Por:
Mayayo-Vallverdu, C, de Heredia, ML, Prat, E, Gonzalez, L, Guarch, ME, Vilches, C, Munoz, L, Asensi, MA, Serra, C, Llebaria, A, Casado, M, Artuch, R, Garrabou, G, Garcia-Roves, PM, Pallardo, FV, Nunes, V
Publicada:
1 ago 2023
Ahead of Print:
1 jul 2023
Resumen:
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.
Filiaciones:
Mayayo-Vallverdu, C:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, LHospitalet De Llobregat, Spain
Univ Barcelona, Hlth Sci & Med Fac, Physiol Sci Dept, Genet Sect, Barcelona, Spain
Hosp Duran i Reynals, Gene Dis & Therapy Program IDIBELL, Mol Genet Lab, 3rd Floor, Gran Via LHosp, 199-203, Barcelona 08908, Spain
Prat, E:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, LHospitalet De Llobregat, Spain
Univ Barcelona, Hlth Sci & Med Fac, Physiol Sci Dept, Genet Sect, Barcelona, Spain
Guarch, ME:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, LHospitalet De Llobregat, Spain
Sidra Med, Immunol Dept, Doha, Qatar
Vilches, C:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, LHospitalet De Llobregat, Spain
Barcelona Inst Sci & Technol, Inst Ciencies Foton ICFO, Castelldefels 08860, Barcelona, Spain
Asensi, MA:
Univ Valencia INCLIVA, Dept Fisiol, Valencia, Spain
Serra, C:
Inst Adv Chem Catalonia IQAC CSIC, SIMChem, Barcelona, Spain
Llebaria, A:
Inst Adv Chem Catalonia IQAC CSIC, SIMChem, Barcelona, Spain
Inst Adv Chem Catalonia IQAC CSIC, Lab Med Chem, MCS, Barcelona, Spain
Casado, M:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER C, Madrid, Spain
Hosp St Joan Deu, Inst Recerca St Joan Deu, Clin Biochem Dept, Esplugas de Llobregat, Spain
Artuch, R:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER C, Madrid, Spain
Hosp St Joan Deu, Inst Recerca St Joan Deu, Clin Biochem Dept, Esplugas de Llobregat, Spain
Garrabou, G:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER C, Madrid, Spain
Univ Barcelona, Hosp Clin Barcelona, Cellex Inst Invest Biomed August Pi i Sunyer IDIBA, Fac Med & Hlth Sci,Internal Med Dept,Muscle Res &, Barcelona, Spain
Garcia-Roves, PM:
Univ Barcelona, Sch Med & Hlth Sci, Dept Physiol Sci, Nutr Metab & Gene therapy Grp,Diabet & Metab Progr, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr C, Madrid 28029, Spain
Pallardo, FV:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER C, Madrid, Spain
Univ Valencia INCLIVA, Dept Fisiol, Valencia, Spain
Nunes, V:
Hosp Duran i Reynals, Gene Dis & Therapy Program IDIBELL, Mol Genet Lab, 3rd Floor, Gran Via LHosp, 199-203, Barcelona 08908, Spain
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