{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:51:15Z","timestamp":1775494275869,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/20082-7"],"award-info":[{"award-number":["2015\/20082-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/23599-6"],"award-info":[{"award-number":["2017\/23599-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IN202919"],"award-info":[{"award-number":["IN202919"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03b1) 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-\u03b1 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-\u03b1 deletion protected against these alterations. Moreover, we observed that cisplatin induced down-regulation of organic transporters MATE-1 and OCT-2 and that PPAR-\u03b1 deletion restored the expression of these transporters. In addition, PPAR-\u03b1 knockout mice at basal state showed increased MATE-1 expression and reduced OCT-2 levels. Here, we show for the first time that PPAR-\u03b1 deletion protects against cisplatin nephrotoxicity and that this protection is via modulation of the organic transporters MATE-1 and OCT-2.<\/jats:p>","DOI":"10.3390\/ijms21197416","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T08:52:41Z","timestamp":1602147161000},"page":"7416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["PPAR-\u03b1 Deletion Attenuates Cisplatin Nephrotoxicity by Modulating Renal Organic Transporters MATE-1 and OCT-2"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9550-6095","authenticated-orcid":false,"given":"Leandro Ceotto","family":"Freitas-Lima","sequence":"first","affiliation":[{"name":"Departamento de Biof\u00edsica, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Budu","sequence":"additional","affiliation":[{"name":"Departamento de Biof\u00edsica, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano Cleis","family":"Arruda","sequence":"additional","affiliation":[{"name":"Departamento de Biof\u00edsica, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"},{"name":"Departamento de Medicina, Disciplina de Nefrologia, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro S\u00e9rgio","family":"Perilh\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Biof\u00edsica, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"},{"name":"Departamento de Medicina, Disciplina de Nefrologia, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-5092","authenticated-orcid":false,"given":"Jonatan","family":"Barrera-Chimal","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"},{"name":"Unidad de Investigaci\u00f3n UNAM-INC, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0095-4608","authenticated-orcid":false,"given":"Ronaldo Carvalho","family":"Araujo","sequence":"additional","affiliation":[{"name":"Departamento de Biof\u00edsica, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"},{"name":"Departamento de Medicina, Disciplina de Nefrologia, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7347-1669","authenticated-orcid":false,"given":"Gabriel Rufino","family":"Estrela","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Disciplina de Nefrologia, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039032, Brazil"},{"name":"Departamento de Oncologia Cl\u00ednica e Experimental, Disciplina de Hematologia e Hematoterapia, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04037002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.3390\/toxins2112490","article-title":"Mechanisms of Cisplatin nephrotoxicity","volume":"2","author":"Miller","year":"2010","journal-title":"Toxins (Basel)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.ki.5002786","article-title":"Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies","volume":"73","author":"Pabla","year":"2008","journal-title":"Kidney Int."},{"key":"ref_3","first-page":"2340","article-title":"Distribution and disposition of platinum following intravenous administration of cis-diamminedichloroplatinum(II) (NSC 119875) to dogs","volume":"36","author":"Litterst","year":"1976","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.bbagen.2013.12.007","article-title":"Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephrotoxicity","volume":"1840","author":"Kodama","year":"2014","journal-title":"Biochim. 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