Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats
Aim: In view of the exploration of sirolimus (rapamycin) as balloon coating for peripheral intravasal treatment and the reports on unfavorable tolerance of daily low-dose sirolimus, the aim of the study was to investigate potential toxicological effects of a single intravascular dose of sirolimus in...
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Elsevier
2025-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X25000349 |
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| author | Jing Xie Denise Schuett Ulrich Speck Tobias Haase |
| author_facet | Jing Xie Denise Schuett Ulrich Speck Tobias Haase |
| author_sort | Jing Xie |
| collection | DOAJ |
| description | Aim: In view of the exploration of sirolimus (rapamycin) as balloon coating for peripheral intravasal treatment and the reports on unfavorable tolerance of daily low-dose sirolimus, the aim of the study was to investigate potential toxicological effects of a single intravascular dose of sirolimus in comparison to paclitaxel and vehicle in the rat. Methods: Rats were treated intravenously with a single dose of 20 mg/kg sirolimus or paclitaxel dissolved in identical vehicle and sacrificed 5- or 14-days post treatment. Vehicle (Cremophor EL/Ethanol diluted with saline) treated rats served as a control. Potential effects on survival, hematology, organ weights, organ histology were analyzed. Results: Single dose i.v. injection of sirolimus, paclitaxel and vehicle induced temporary sedation after treatment. One animal treated with paclitaxel died, probably due to solvent toxicity. Sirolimus, paclitaxel and the vehicle control were tolerated. Animals treated with sirolimus or paclitaxel showed temporary hematological effects and thymic atrophy that subsided after 14 days. Sirolimus induced a temporary weight reduction of ovaries and uterus. Male rats showed histological changes of testes at 14 days after sirolimus treatment. Notably, sirolimus induced a prolonged body weight reduction compared to paclitaxel and vehicle treatment in male rats. Conclusion: Both substances showed similar and acceptable tolerability after high single-dose intravenous treatment. The results of this study do not indicate safety concerns that would preclude the use of sirolimus as an active ingredient on balloon catheters as an alternative to paclitaxel. |
| format | Article |
| id | doaj-art-44a95974afcf478692ee7c1be08ffcca |
| institution | Kabale University |
| issn | 2666-027X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj-art-44a95974afcf478692ee7c1be08ffcca2025-08-20T03:29:31ZengElsevierCurrent Research in Toxicology2666-027X2025-01-01910024810.1016/j.crtox.2025.100248Comparative acute toxicity of intravenous paclitaxel and sirolimus in ratsJing Xie0Denise Schuett1Ulrich Speck2Tobias Haase3Department of Radiology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; InnoRa GmbH, Berlin, GermanyInnoRa GmbH, Berlin, GermanyDepartment of Radiology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; InnoRa GmbH, Berlin, GermanyDepartment of Radiology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; InnoRa GmbH, Berlin, Germany; Corresponding author.Aim: In view of the exploration of sirolimus (rapamycin) as balloon coating for peripheral intravasal treatment and the reports on unfavorable tolerance of daily low-dose sirolimus, the aim of the study was to investigate potential toxicological effects of a single intravascular dose of sirolimus in comparison to paclitaxel and vehicle in the rat. Methods: Rats were treated intravenously with a single dose of 20 mg/kg sirolimus or paclitaxel dissolved in identical vehicle and sacrificed 5- or 14-days post treatment. Vehicle (Cremophor EL/Ethanol diluted with saline) treated rats served as a control. Potential effects on survival, hematology, organ weights, organ histology were analyzed. Results: Single dose i.v. injection of sirolimus, paclitaxel and vehicle induced temporary sedation after treatment. One animal treated with paclitaxel died, probably due to solvent toxicity. Sirolimus, paclitaxel and the vehicle control were tolerated. Animals treated with sirolimus or paclitaxel showed temporary hematological effects and thymic atrophy that subsided after 14 days. Sirolimus induced a temporary weight reduction of ovaries and uterus. Male rats showed histological changes of testes at 14 days after sirolimus treatment. Notably, sirolimus induced a prolonged body weight reduction compared to paclitaxel and vehicle treatment in male rats. Conclusion: Both substances showed similar and acceptable tolerability after high single-dose intravenous treatment. The results of this study do not indicate safety concerns that would preclude the use of sirolimus as an active ingredient on balloon catheters as an alternative to paclitaxel.http://www.sciencedirect.com/science/article/pii/S2666027X25000349PaclitaxelSirolimusIntravenousToxicityRats |
| spellingShingle | Jing Xie Denise Schuett Ulrich Speck Tobias Haase Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats Current Research in Toxicology Paclitaxel Sirolimus Intravenous Toxicity Rats |
| title | Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats |
| title_full | Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats |
| title_fullStr | Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats |
| title_full_unstemmed | Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats |
| title_short | Comparative acute toxicity of intravenous paclitaxel and sirolimus in rats |
| title_sort | comparative acute toxicity of intravenous paclitaxel and sirolimus in rats |
| topic | Paclitaxel Sirolimus Intravenous Toxicity Rats |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X25000349 |
| work_keys_str_mv | AT jingxie comparativeacutetoxicityofintravenouspaclitaxelandsirolimusinrats AT deniseschuett comparativeacutetoxicityofintravenouspaclitaxelandsirolimusinrats AT ulrichspeck comparativeacutetoxicityofintravenouspaclitaxelandsirolimusinrats AT tobiashaase comparativeacutetoxicityofintravenouspaclitaxelandsirolimusinrats |