Your browser doesn't support javascript.
loading
Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment.
Zahedi, Kamyar; Barone, Sharon; Brooks, Marybeth; Stewart, Tracy Murray; Foley, Jackson R; Nwafor, Ashley; Casero, Robert A; Soleimani, Manoocher.
Afiliação
  • Zahedi K; Division of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
  • Barone S; Research Services, New Mexico Veterans Health Care Center, Albuquerque, NM 87108, USA.
  • Brooks M; Division of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
  • Stewart TM; Research Services, New Mexico Veterans Health Care Center, Albuquerque, NM 87108, USA.
  • Foley JR; Division of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
  • Nwafor A; Research Services, New Mexico Veterans Health Care Center, Albuquerque, NM 87108, USA.
  • Casero RA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Soleimani M; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Biomedicines ; 12(3)2024 Mar 13.
Article em En | MEDLINE | ID: mdl-38540254
ABSTRACT
Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N1-acetyltransferase, Sat1, and spermine oxidase, Smox) and decreased expression of ornithine decarboxylase (Odc1), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC. Upon confirmation of the RNA-seq results, we tested the hypothesis that enhanced polyamine catabolism contributes to the onset of renal injury and development of fibrosis. To test our hypothesis, we compared the severity of RLDC-induced renal injury and fibrosis in wildtype (WT), Sat1-KO, and Smox-KO mice. Our results suggest that the ablation of polyamine catabolic enzymes reduces the severity of renal injury and that modulation of the activity of these enzymes may protect against kidney damage and fibrosis caused by cisplatin treatment.
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Biomedicines Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Biomedicines Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos