title: Intraperitoneal administration of high doses of polyethylene glycol (PEG) causes hepatic subcapsular necrosis and low-grade peritonitis with a rise in hepatic biomarkers.
abstract: Polyethylene glycols (PEGs) are commonly employed as excipients in preclinical studies and in vitro experiments to dissolve poorly hydrosoluble drugs. Their use is generally considered safe in both animals and humans; however, limited data is available concerning the safety of PEGs when administered parenterally. The results of our investigation demonstrate that PEG-400 can have an irritant effect on serosal surfaces and causes subcapsular hepatocellular necrosis in mice when administered intraperitoneally at a high dose (4 mL/kg). Accordingly, levels of serum biomarkers of liver injury need to be carefully interpreted in studies where PEG is administered intraperitoneally and always in association with the results of the histological assessment.
authors.affiliation: Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool, UK; Veterinary Pathology, School of Veterinary Science, University of Liverpool, UK; MRC Centre for Drug Safety Science, University of Liverpool, UK. Electronic address: pellegg@liv.ac.uk.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellegrini
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Starkey Lewis
authors.forename: Luke
authors.initials: L
authors.lastname: Palmer
authors.forename: Udo
authors.initials: U
authors.lastname: Hetzel
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Goldring
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Williams
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D011092:Polyethylene Glycols
keywords: Excipients; Hepatic biomarkers; Hepatic subcapsular necrosis; Peritonitis; Polyethylene glycol