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Despite evidence supporting an indirect mechanism of action, key mechanistic aspects have yet to be fully clarified. This study aimed to evaluate whether\n                      <jats:sc>l<\/jats:sc>\n                      -Erg can prevent stone progression in cystinuria and in other types of lithiasis, such as calcium oxalate nephrolithiasis, and to further elucidate its mechanistic basis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Using mouse models,\n                      <jats:sc>l<\/jats:sc>\n                      -Erg significantly reduced cystine stone growth and renal inflammation, and its combination with\n                      <jats:sc>d<\/jats:sc>\n                      -penicillamine enhanced stone dissolution and mitigated drug-related toxicity. In calcium oxalate nephrolithiasis,\n                      <jats:sc>l<\/jats:sc>\n                      -Erg decreased crystal deposition, preserved renal architecture, normalized glutathione levels, and restored mitochondrial respiration. Transcriptomic analysis revealed downregulation of immune pathways and activation of cell cycle genes, suggesting attenuation of inflammation and promotion of tubular repair.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>\n                      This study is the first to demonstrate that\n                      <jats:sc>l<\/jats:sc>\n                      -Erg exerts renoprotective effects through combined antioxidant and mitochondrial mechanisms in two major forms of nephrolithiasis and introduces a dual therapeutic approach combining an antioxidant with a cystine-solubilizing agent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      By targeting oxidative stress and mitochondrial dysfunction,\n                      <jats:sc>l<\/jats:sc>\n                      -Erg represents a promising therapeutic strategy for nephrolithiasis, either alone or as an adjunct to current treatments.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      44, 878\u2013891.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261431276","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:03:01Z","timestamp":1773291781000},"page":"878-891","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>L<\/scp>\n                    -Ergothioneine Attenuates Nephrolithiasis by Modulating Redox Signaling and Mitochondrial Function in Cystine and Calcium Oxalate Models"],"prefix":"10.1177","volume":"44","author":[{"given":"Clara","family":"Mayayo-Vallverd\u00fa","sequence":"first","affiliation":[{"name":"Genes, Disease and Therapy Program, Human Molecular Genetics Group-IDIBELL, L\u2019Hospitalet de Llobregat, Spain."},{"name":"Genetics Section, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain."},{"name":"Neuroscience Program, IDIBELL, Physiology Unit, Department of Physiological Sciences, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona-IDIBELL, L\u2019Hospitalet de Llobregat, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vecino-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Genes, Disease and Therapy Program, Human Molecular Genetics Group-IDIBELL, L\u2019Hospitalet de Llobregat, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Prat","sequence":"additional","affiliation":[{"name":"Genes, Disease and Therapy Program, Human Molecular Genetics Group-IDIBELL, L\u2019Hospitalet de Llobregat, Spain."},{"name":"Genetics Section, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain."},{"name":"Neuroscience Program, IDIBELL, Physiology Unit, Department of Physiological Sciences, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona-IDIBELL, L\u2019Hospitalet de Llobregat, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Cutanda-Tesouro","sequence":"additional","affiliation":[{"name":"Diabetis and Metabolism Program, IDIBELL, Biophysical Section, Department of Physiological Sciences, School of Medicine and Health Sciences, University of Barcelona, L\u2019Hospitalet de Llobregat, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Ormazabal","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, Barcelona, Spain."},{"name":"Centro de Investigaci\u00f3n en red de enfermedades raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, Barcelona, Spain."},{"name":"Centro de Investigaci\u00f3n en red de enfermedades raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Larriba","sequence":"additional","affiliation":[{"name":"Genes, Disease and Therapy Program, Human Molecular Genetics Group-IDIBELL, L\u2019Hospitalet de Llobregat, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Asensi","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda. 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