| Texto completo | |
| Autor(es): |
Freitas-Lima, Leandro Ceotto
[1]
;
Budu, Alexandre
[1]
;
Arruda, Adriano Cleis
[1, 2]
;
Perilhao, Mauro Sergio
[1, 2]
;
Barrera-Chimal, Jonatan
[3, 4]
;
Araujo, Ronaldo Carvalho
[1, 2]
;
Estrela, Gabriel Rufino
[2, 5]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Univ Fed Sao Paulo, Dept Biofis, BR-04039032 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Med, Disciplina Nefrol, BR-04039032 Sao Paulo - Brazil
[3] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF - Mexico
[4] Inst Nacl Cardiol Ignacio Chavez, Unidad Invest UNAM INC, Mexico City 14080, DF - Mexico
[5] Univ Fed Sao Paulo, Dept Oncol Clin & Expt, Disciplina Hematol & Hematoterapia, BR-04037002 Sao Paulo - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 19 OCT 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
Cisplatin is a chemotherapy drug widely used in the treatment of solid tumors. However, nephrotoxicity has been reported in about one-third of patients undergoing cisplatin therapy. Proximal tubules are the main target of cisplatin toxicity and cellular uptake; elimination of this drug can modulate renal damage. Organic transporters play an important role in the transport of cisplatin into the kidney and organic cations transporter 2 (OCT-2) has been shown to be one of the most important transporters to play this role. On the other hand, multidrug and toxin extrusion 1 (MATE-1) transporter is the main protein that mediates the extrusion of cisplatin into the urine. Cisplatin nephrotoxicity has been shown to be enhanced by increased OCT-2 and/or reduced MATE-1 activity. Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is the transcription factor which controls lipid metabolism and glucose homeostasis; it is highly expressed in the kidneys and interacts with both MATE-1 and OCT-2. Considering the above, we treated wild-type and PPAR-alpha knockout mice with cisplatin in order to evaluate the severity of nephrotoxicity. Cisplatin induced renal dysfunction, renal inflammation, apoptosis and tubular injury in wild-type mice, whereas PPAR-alpha deletion protected against these alterations. Moreover, we observed that cisplatin induced down-regulation of organic transporters MATE-1 and OCT-2 and that PPAR-alpha deletion restored the expression of these transporters. In addition, PPAR-alpha knockout mice at basal state showed increased MATE-1 expression and reduced OCT-2 levels. Here, we show for the first time that PPAR-alpha deletion protects against cisplatin nephrotoxicity and that this protection is via modulation of the organic transporters MATE-1 and OCT-2. (AU) | |
| Processo FAPESP: | 17/23599-6 - Receptores de cininas e imunometabolismo |
| Beneficiário: | Leandro Ceotto Freitas Lima |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 15/20082-7 - Sistema calicreína cininas no exercício físico e metabolismo |
| Beneficiário: | Ronaldo de Carvalho Araújo |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |