Genistein improves renal disease in a mouse model of nephropathic cystinosis: a comparison study with cysteamine.

Abstract

Cysteamine is currently the only therapy for nephropathic cystinosis. It significantly improves life expectancy and delays progression to end-stage kidney disease; however, it cannot prevent it. Unfortunately, compliance to therapy is often weak, particularly during adolescence. Therefore, finding better treatments is a priority in the field of cystinosis. Previously, we found that genistein, an isoflavone particularly enriched in soy, can revert part of the cystinotic cellular phenotype that is not sensitive to cysteamine in vitro. To test the effects of genistein in vivo, we fed 2-month-old wild-type and Ctns-/- female mice with either a control diet, a genistein-containing diet or a cysteamine-containing diet for 14 months. Genistein (160 mg/kg/day) did not affect the growth of the mice or hepatic functionality. Compared with untreated mice at 16 months, Ctns-/- mice fed with genistein had lower cystine concentrations in their kidneys, reduced formation of cystine crystals, a smaller number of LAMP1-positive structures and an overall better-preserved parenchymal architecture. Cysteamine (400 mg/kg/day) was efficient in reverting the lysosomal phenotype and in preventing the development of renal lesions. These preclinical data indicate that genistein ameliorates kidney injury resulting from cystinosis with no side effects. Genistein therapy represents a potential treatment to improve the outcome for patients with cystinosis.

• Authors: Ester De Leo, Anna Taranta, Roberto Raso, Elena Polishchuk, Valentina D'Oria, Marco Pezzullo, Bianca Maria Goffredo, Sara Cairoli, Francesco Bellomo, Giulia Battafarano, Francesca Diomedi Camassei, Andrea Del Fattore, Roman Polishchuk, Francesco Emma, Laura Rita Rega
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 32 Issue 7 Pg. 1090-1101 (03 20 2023) ISSN: 1460-2083 [Electronic] England
• PMID: 36300303 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Cysteamine
• Cystine
• Genistein

Topics

• Animals
• Female
• Mice
• Cysteamine (therapeutic use)
• Cystine (therapeutic use)
• Cystinosis (drug therapy, genetics)
• Disease Models, Animal
• Genistein (pharmacology, therapeutic use)
• Kidney
• Kidney Diseases