Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism
Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic ren...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2021-10-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2021001200602&tlng=en |
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| author | A. Budu L.C. Freitas-Lima A.C. de Arruda M.S. Perilhão J. Barrera-Chimal R.C. Araújo G.R. Estrela |
| author_facet | A. Budu L.C. Freitas-Lima A.C. de Arruda M.S. Perilhão J. Barrera-Chimal R.C. Araújo G.R. Estrela |
| author_sort | A. Budu |
| collection | DOAJ |
| description | Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process. |
| first_indexed | 2024-12-20T10:36:08Z |
| format | Article |
| id | doaj.art-e0db924711e84bd28c307eb381a55bd9 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-12-20T10:36:08Z |
| publishDate | 2021-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-e0db924711e84bd28c307eb381a55bd92022-12-21T19:43:37ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2021-10-01541210.1590/1414-431x2021e11353Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonismA. Buduhttps://orcid.org/0000-0002-7110-9754L.C. Freitas-Limahttps://orcid.org/0000-0001-9550-6095A.C. de Arrudahttps://orcid.org/0000-0003-0788-0154M.S. Perilhãohttps://orcid.org/0000-0002-7509-1651J. Barrera-Chimalhttps://orcid.org/0000-0002-0711-5092R.C. Araújohttps://orcid.org/0000-0003-0095-4608G.R. Estrelahttps://orcid.org/0000-0003-2858-5111Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2021001200602&tlng=enChronic kidney diseaseCisplatin nephrotoxicityRenal fibrosisKininsKinin B1 receptor |
| spellingShingle | A. Budu L.C. Freitas-Lima A.C. de Arruda M.S. Perilhão J. Barrera-Chimal R.C. Araújo G.R. Estrela Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism Brazilian Journal of Medical and Biological Research Chronic kidney disease Cisplatin nephrotoxicity Renal fibrosis Kinins Kinin B1 receptor |
| title | Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism |
| title_full | Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism |
| title_fullStr | Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism |
| title_full_unstemmed | Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism |
| title_short | Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism |
| title_sort | renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin b1 receptor antagonism |
| topic | Chronic kidney disease Cisplatin nephrotoxicity Renal fibrosis Kinins Kinin B1 receptor |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2021001200602&tlng=en |
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