An implanted port-catheter system for repeated hepatic arterial infusion of low-density lipoprotein-docosahexaenoic acid nanoparticles in normal rats: A safety study
| Autor: | Jeffrey G. McDonald, Junjie Li, Yuzhu Wang, Indhumathy Subramaniyan, Hongwei Zhang, Mary Wight-Carter, William C. Putnam, Jaideep Chaudhary, Gonçalo Vale, Tao Qin, Arnida Anwar, Ian R. Corbin |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Blood Glucose Male medicine.medical_specialty Docosahexaenoic Acids Renal function Pharmacology Toxicology Kidney Function Tests Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Hepatic arterial infusion Catheters Indwelling Hepatic Artery Lipid oxidation Liver Function Tests Medicine Animals Infusions Intra-Arterial Tissue Distribution Rats Wistar medicine.diagnostic_test business.industry Lipids Lipoproteins LDL Catheter 030104 developmental biology chemistry Liver Docosahexaenoic acid 030220 oncology & carcinogenesis Low-density lipoprotein Nanoparticles Histopathology lipids (amino acids peptides and proteins) business Lipid profile |
| Zdroj: | Toxicol Appl Pharmacol |
| ISSN: | 1096-0333 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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