An implanted port-catheter system for repeated hepatic arterial infusion of low-density lipoprotein-docosahexaenoic acid nanoparticles in normal rats: A safety study

Yuzhu Wang, Junjie Li, Indhumathy Subramaniyan, Goncalo Dias do Vale, Jaideep Chaudhary, Arnida Anwar, Mary Wight-Carter, Jeffrey G. McDonald, William C. Putnam, Tao Qin, Hongwei Zhang, Ian R. Corbin

Research output: Contribution to journalArticle

Abstract

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-κβ, 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.

Original languageEnglish (US)
Article number115037
JournalToxicology and Applied Pharmacology
Volume400
DOIs
StatePublished - Aug 1 2020

Keywords

  • Docosahexaenoic acid
  • Lipid oxidation
  • Low-density lipoprotein
  • Nanoparticle
  • Nanoparticle safety
  • Port-catheter systems

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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