Dapagliflozin protects against doxorubicin-induced nephrotoxicity associated with nitric oxide pathway-A translational study.
Free Radic Biol Med
; 208: 103-111, 2023 11 01.
Article
em En
| MEDLINE
| ID: mdl-37549754
ABSTRACT
Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Renal
/
Inibidores do Transportador 2 de Sódio-Glicose
/
Nefropatias
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article