{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:45:27Z","timestamp":1766137527815,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["18-75-10017"],"award-info":[{"award-number":["18-75-10017"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an established form of locoregional chemotherapy of peritoneum tumors. However, its efficacy and safety status remain a controversy, partially, due to scarce data on pharmacokinetics and toxicity profile of drugs under HIPEC. In the current study, 24 female Wistar rats were randomly assigned to receive cisplatin as HIPEC (n = 12, 20 mg\/kg) or intravenously (i.v., n = 9, 4 mg\/kg). The subgroups of three animals were used for the initial, intermediate, and late phases of the pharmacokinetic assessment. The animals were sacrificed on days 1 and 5. Blood, liver, kidney, and ovaries were evaluated for platinum content. Histological and immunohistochemical evaluation was undertaken in the liver and kidney. A trend for higher blood plasma platinum levels was observed for HIPEC compared to i.v. Significantly lower (p &lt; 0.001) relative platinum binding to the proteins was observed in HIPEC animals compared to the i.v. administration. A five-fold higher concentration of cisplatin in HIPEC resulted in a ca. 2.5-fold increase in total blood platinum and ca. two-fold increase in blood ultrafitrable platinum (\u201cfree\u201d Pt). Immunohistochemistry revealed higher kidney and liver damage after i.v. administration of cisplatin compared to HIPEC, although a five-fold higher dose of cisplatin was applied in HIPEC. Together with relatively lower absorption to the systemic circulation in HIPEC, higher protein binding is probably the primary reason for lower observed toxicity in HIPEC animals.<\/jats:p>","DOI":"10.3390\/molecules25204733","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T08:14:50Z","timestamp":1602922490000},"page":"4733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution"],"prefix":"10.3390","volume":"25","author":[{"given":"Galina","family":"Kireeva","sequence":"first","affiliation":[{"name":"N.N. Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-4637","authenticated-orcid":false,"given":"Stepan","family":"Kruglov","sequence":"additional","affiliation":[{"name":"N.N. Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2264-4857","authenticated-orcid":false,"given":"Mikhail","family":"Maydin","sequence":"additional","affiliation":[{"name":"N.N. Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-6086","authenticated-orcid":false,"given":"Ekaterina","family":"Gubareva","sequence":"additional","affiliation":[{"name":"N.N. Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Fedoros","sequence":"additional","affiliation":[{"name":"N.N. Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Zubakina","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Federal Medical Biological Agency, 192019 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya","family":"Ivanenko","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Federal Medical Biological Agency, 192019 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Bezruchko","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Federal Medical Biological Agency, 192019 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-6963","authenticated-orcid":false,"given":"Nikolay","family":"Solovyev","sequence":"additional","affiliation":[{"name":"Institute of Technology Sligo, Ash Lane, F91 YW50 Sligo, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12309","DOI":"10.1021\/ja9625079","article-title":"Crystal structure of the anticancer drug cisplatin bound to duplex DNA","volume":"118","author":"Takahara","year":"1996","journal-title":"J. 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