期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 400, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2020.115037
关键词
Nanoparticle; Low-density lipoprotein; Docosahexaenoic acid; Lipid oxidation; Port-catheter systems; Nanoparticle safety
资金
- Remeditex venturesLCC [OTD-109946]
- NCI, National Institutes of Health (NIH) [R01CA215702]
- Henan Provincial Health System: Study Abroad 5451 Project [2016051]
- UTSW Cancer Center Support Grant [5P30 CA 142543-05]
- UTSW Cancer Prevention Research Institute of Texas Core Facilities Support Award [RP170003]
Background: In recent years, small animal arterial port-catheter systems have been implemented in rodents with reasonable success. The aim of the current study is to employ the small animal port-catheter system to evaluate the safety of multiple hepatic-artery infusions (HAI) of low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticles to the rat liver. Methods: Wistar rats underwent surgical placement of indwelling HAI ports. Repeated administrations of PBS or LDL-DHA nanoparticles were performed through the port at baseline and days 3 and 6. Rats were sacrificed on day 9 at which point blood and various organs were collected for histopathology and biochemical analyses. Results: The port-catheter systems were implanted successfully and repeated infusions of PBS or LDL-DHA nanoparticles were tolerated well by all animals over the duration of the study. Measurements of serum liver/renal function tests, glucose and lipid levels did not differ between control and LDL-DHA treated rats. The liver histology was unremarkable in the LDL-DHA treated rats and the expression of hepatic inflammatory regulators (NF-kappa beta, IL-6 and CRP) were similar to control rats. Repeated infusions of LDL-DHA nanoparticles did not alter liver glutathione content or the lipid profile in the treated rats. The DHA extracted by the liver was preferentially metabolized to the anti-inflammatory DHA-derived mediator, protectin DX. Conclusion: Our findings indicate that repeated HAI of LDL-DHA nanoparticles is not only well tolerated and safe in the rat, but may also be protective to the liver.
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