| Texto completo | |
| Autor(es): |
Fogaca-Ruiz, Fernanda
;
Falconi, Carlos Alexandre
;
Parletta, Aline Cristina
;
Sanz, Carmen Lucia
;
Nakao, Lia Sumie
;
Carneiro-Ramos, Marcela Sorelli
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Biochemical and Biophysical Research Communications; v. 789, p. 13-pg., 2025-10-25. |
| Resumo | |
Indoxyl sulfate (IS), a uremic toxin derived from tryptophan metabolism, accumulates in renal dysfunction and contributes to kidney fibrosis, cardiac hypertrophy, and vascular damage via reactive oxygen species (ROS). This study investigated IS effects in a model of acute kidney injury (AKI) induced by unilateral ischemia-reperfusion (IR) of the left kidney in male C57BL/6 mice. Mice underwent IR surgery and received IS (100 mg/kg/day, intraperitoneally) for 15 days. After euthanasia, we assessed kidney and heart morphology, biochemical markers (urea, creatinine, BUN), and the expression of injury- and inflammation-related genes. IR successfully induced AKI, increasing kidney mass and upregulating renal injury markers (KIM-1, Cystatin-C, NGAL) and proinflammatory cytokines (IL-6, IL-1(3, TNF-alpha, TGF-(3). IS treatment exacerbated KIM-1, Cystatin-C, IL-1(3, and TGF-(3 expression versus IR alone, indicating aggravated renal injury. No changes occurred in IL-10, cardiac morphology, or molecular markers. IS reduced OATs 1 and 3 expression in injured kidneys and elevated plasma IS levels in the IR + IS group, while p-cresyl sulfate remained undetectable. Histological analysis revealed increased renal fibrosis post-IR, but IS did not further amplify fibrosis in kidneys or hearts. These findings suggest IS worsens renal inflammation and injury in AKI without detectable cardiac effects. Understanding IS's role in AKI may provide insights into the transition from AKI to chronic kidney disease (CKD) and clarify mechanisms of uremic toxin toxicity. (AU) | |
| Processo FAPESP: | 22/00153-0 - Biofotônica aplicada ao estudo de vesículas extracelulares como conectores da conversa rim-coração |
| Beneficiário: | Marcela Sorelli Carneiro Ramos |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 24/21516-0 - Síndrome cardiorrenal e inflamação: elos perdidos no hipotiroidismo? |
| Beneficiário: | Aline Cristina Parletta |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 24/02928-5 - Remodelamento estrutural e elétrico cardíaco durante a transição da lesão renal aguda para a doença renal crônica. |
| Beneficiário: | Marcela Sorelli Carneiro Ramos |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |