In vivo effect of selective macrophage suppression on the development of intrahepatic cholestasis in mice.
We studied the role of selective suppression of liver Kupffer cells (gadolinium chloride, 14 mg/kg intravenously) in the development of intrahepatic cholestasis in CBA/C57B1/6 mice after intraperitoneal injection of alpha-naphthylisothiocyanate in a single dose of 200 mg/kg. Pretreatment with gadolinium chloride increased the severity of cholestasis and signs of liver damage. Gadolinium accumulation in the liver peaked after 24 h and was accompanied by a decrease in activities of cathepsin D and cathepsin B and concentration of matrix metalloprotease-2. Our results confirm the hypothesis that normal function of Kupffer cells and extracellular matrix plays an important role in cholestasis. Administration of gadolinium chloride serves as a convenient model to study the side effects, toxicity, and safety of lanthanides as nanoparticles.
Korolenko
T A
TA
Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk, Russia. t.a.korolenko@iph.ma.nsc.ru
Klishevich
M S
MS
Cherkanova
M S
MS
Alexeenko
T V
TV
Zhanaeva
S Ya
SY
Savchenko
N G
NG
Goncharova
I A
IA
Filjushina
E E
EE
D015058:1-Naphthylisothiocyanate / Q000494:pharmacology; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced* / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission
D015058:1-Naphthylisothiocyanate; D005682:Gadolinium; D002401:Cathepsin B; D002402:Cathepsin D; D020778:Matrix Metalloproteinase 2; C038958:gadolinium chloride