TY - JOUR
T1 - An implanted port-catheter system for repeated hepatic arterial infusion of low-density lipoprotein-docosahexaenoic acid nanoparticles in normal rats
T2 - A safety study
AU - Wang, Yuzhu
AU - Li, Junjie
AU - Subramaniyan, Indhumathy
AU - do Vale, Goncalo Dias
AU - Chaudhary, Jaideep
AU - Anwar, Arnida
AU - Wight-Carter, Mary
AU - McDonald, Jeffrey G.
AU - Putnam, William C.
AU - Qin, Tao
AU - Zhang, Hongwei
AU - Corbin, Ian R.
N1 - Funding Information:
This work was supported in part by Remeditex ventures LCC OTD-109946 , NCI, National Institutes of Health (NIH), Grant R01CA215702 , the Henan Provincial Health System : Study Abroad 5451 Project ( 2016051 ) and the UTSW Cancer Center Support Grant ( 5P30 CA 142543–05 ) and the Cancer Prevention Research Institute of Texas Core Facilities Support Award ( RP170003 ; to W.C.P.).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Docosahexaenoic acid
KW - Lipid oxidation
KW - Low-density lipoprotein
KW - Nanoparticle
KW - Nanoparticle safety
KW - Port-catheter systems
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U2 - 10.1016/j.taap.2020.115037
DO - 10.1016/j.taap.2020.115037
M3 - Article
C2 - 32417438
AN - SCOPUS:85085348437
SN - 0041-008X
VL - 400
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
M1 - 115037
ER -