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Dapagliflozin treatment ameliorates oxidative stress, apoptosis and inflammation in tenofovir-induced nephrotoxicity in rats

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Autor(es):
dos Santos, Vitor Antonio ; Viotto, Ana Carolina Rocha ; Nascimento, Mariana Moura ; Bernardo, Desiree Rita Denelle ; Shimizu, Maria Heloisa Massola ; de Sena, Claudia Ramos ; Seguro, Antonio Carlos ; Volpini, Rildo Aparecido ; de Braganca, Ana Carolina ; Canale, Daniele
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 15, n. 1, p. 14-pg., 2025-11-29.
Resumo

Tenofovir disoproxil fumarate is a widely prescribed component in antiretroviral therapy regimes frequently associated with nephrotoxicity. Dapagliflozin, an SGLT2 inhibitor, is primarily used as a hypoglycemic agent but is increasingly recognized for its pleiotropic protective effects. To investigate whether dapagliflozin could mitigate tenofovir-induced nephrotoxicity, Wistar rats were randomly assigned to four groups: Control- received a standard diet for 45 days, TDF- received a standard diet added with tenofovir (300 mg/kg food) for 45 days, DAPA- received a standard diet for 45 days added with dapagliflozin (20 mg/kg food) in the last 15 days, and TDF + DAPA- received a standard diet added with tenofovir for 45 days and dapagliflozin in the last 15 days. Dapagliflozin administration restored glomerular filtration rate, improved renal hemodynamic parameters and maintained the adequate balance of TBARS/GSH levels through the modulation of SIRT1/Nrf2/HO-1 signaling pathway and mitochondrial enzymatic antioxidant system-related markers. Furthermore, dapagliflozin treatment reduced inflammatory response and apoptotic cell death, marked by increased Bcl-2 expression and decreased levels of TLR4, NF-kappa B, pro-inflammatory cytokines, Bax, cytochrome c, and caspase-3. Dapagliflozin holds multifaceted renoprotective effects potentially offering a therapeutic strategy to slow the progression of kidney injury in tenofovir-induced nephrotoxicity. (AU)

Processo FAPESP: 22/05519-3 - Participação da sulfotransferase 1C2 na sinalização da vitamina D no modelo de IRA-isquêmica em ratos
Beneficiário:Ana Carolina de Bragança Viciana
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 24/09066-9 - Avaliação do transporte renal hidroeletrolítico, do estresse oxidativo e da apoptose em modelo experimental murino de nefrotoxicidade induzida por Tenofovir e Anfotericina B: efeitos do tratamento com Dapagliflozina.
Beneficiário:Daniele Canale Cavicchioli
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 22/07409-0 - Avaliação da progressão da doença renal em ratos obesos e deficientes em vitamina D após insulto de isquemia/reperfusão renal e dos efeitos alternativos da dapaglifozina sobre o comprometimento renal em modelo de nefrectomia 5/6 associado à Obesidade
Beneficiário:Rildo Aparecido Volpini
Modalidade de apoio: Auxílio à Pesquisa - Regular