1. Long-term effects of luteolin in a mouse model of nephropathic cystinosis
- Author
-
Ester De Leo, Anna Taranta, Roberto Raso, Marco Pezzullo, Michela Piccione, Valentina Matteo, Alessia Vitale, Francesco Bellomo, Bianca Maria Goffredo, Francesca Diomedi Camassei, Giusi Prencipe, Laura Rita Rega, and Francesco Emma
- Subjects
Cystinosis ,Fanconi syndrome ,Luteolin ,Apoptosis ,Lysosome ,Autophagy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
In infantile nephropathic cystinosis, variants of the CTNS gene cause accumulation of cystine in lysosomes, causing progressive damage to most organs. Patients usually present before 1 year of age with signs of renal Fanconi syndrome. Cysteamine therapy allows cystine clearance from lysosomes and delays kidney damage but does not prevent progression to end-stage kidney disease, suggesting that pathways unrelated to cystine accumulation are also involved. Among these, impaired autophagy, altered endolysosomal trafficking, and increased apoptosis have emerged in recent years as potential targets for new therapies. We previously showed that luteolin, a flavonoid compound, improves these abnormal pathways in cystinotic cells and in zebrafish models of the disease. Herein, we have investigated if prolonged luteolin treatment ameliorates kidney damage in a murine model of cystinosis. To this end, we have treated Ctns-/- mice from 2 to 8 months with 150 mg/kg/day of luteolin. No significant side effects were observed. Compared to untreated animals, analyses of kidney cortex samples obtained after sacrifice showed that luteolin decreased p62/SQSTM1 levels (p
- Published
- 2024
- Full Text
- View/download PDF