Yuzhu Wang1, Junjie Li2, Indhumathy Subramaniyan3, Goncalo Dias do Vale4, Jaideep Chaudhary2, Arnida Anwar2, Mary Wight-Carter5, Jeffrey G McDonald4, William C Putnam3, Tao Qin6, Hongwei Zhang6, Ian R Corbin7. 1. Department of Hepatobiliary and pancreatic surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. 2. Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. 3. Department of Pharmaceutical Sciences, Department of Pharmacy Practice within the Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX 75235, USA. 4. Department of Molecular Genetics, Dallas, TX 75390, USA. 5. Animal Resource Center, Dallas, TX 75390, USA. 6. Department of Hepatobiliary and pancreatic surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China. 7. Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Internal Medicine Division of Liver and Digestive Diseases, Dallas, TX 75390, USA; RadiologyUniversity of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address: ian.corbin@utsouthwestern.edu.
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.
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.
Authors: Charles N Serhan; Katherine Gotlinger; Song Hong; Yan Lu; Jeffrey Siegelman; Tamara Baer; Rong Yang; Sean P Colgan; Nicos A Petasis Journal: J Immunol Date: 2006-02-01 Impact factor: 5.422