The impact of poloxamer 407 on the ultrastructure of the liver and evidence for clearance by extensive endothelial and kupffer cell endocytosis.
Poloxamer 407 (P407) is a non-ionic detergent that is used widely in pharmaceutical formulations and personal care products. In animals, P407 causes hyperlipidaemia. P407 is taken up by the liver and causes loss of fenestrations in liver sinusoidal endothelial cells (LSEC), which contributes to the pathogenesis of hyperlipidaemia. Here the short-term (1-15 days) effects of P407 on all liver cells were investigated in mice using electron and light microscopy. As expected, P407 was associated with hyperlipidaemia. Kupffer cells became massively engorged with vacuoles and took on a marked honeycomb morphology. LSECs also became engorged with vacuoles and endocytosis was activated. The diameter of lipoproteins in the space of Disse was less than those in the lumen, consistent with a filtering effect of fenestrations. Defenestration of the LSEC was noted. Hepatocyte endocytosis of lipoproteins and P407 particles was also noted; however, hepatocyte steatosis was not evident. Hepatic stellate cells did not appear to be abnormal. In conclusion, P407 is taken up by the liver mostly through endocytosis by LSECs and Kupffer cells.
Centre for Education and Research on Ageing and the ANZAC Research Institute, University of Sydney and Concord Hospital, Sydney, Australia.
Alessandra
A
Warren
Volker
V
Benseler
Victoria C
VC
Cogger
Patrick
P
Bertolino
David G
DG
Le Couteur
D000818:Animals; D004705:Endocytosis; D042783:Endothelial Cells / Q000473:pathology* / Q000648:ultrastructure; D055166:Hepatic Stellate Cells / Q000473:pathology / Q000648:ultrastructure; D022781:Hepatocytes / Q000648:ultrastructure; D006949:Hyperlipidemias / Q000209:etiology; D007700:Kinetics; D007728:Kupffer Cells / Q000473:pathology* / Q000648:ultrastructure; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D020442:Poloxamer / Q000493:pharmacokinetics* / Q000633:toxicity*
D008074:Lipoproteins; D020442:Poloxamer