Stem cell factor attenuates liver damage in a murine model of acetaminophen-induced hepatic injury.
Acute liver injury is a common cause of intensive care unit visits. In these studies, we used a murine model of acetaminophen poisoning to examine the role of stem cell factor (SCF) on liver damage. In the initial studies, we identified that the liver produces relatively high constitutive levels of SCF. Upon administration of acetaminophen, the levels of SCF fell dramatically, correlating to damage within the liver. When the liver was allowed to regenerate, the levels of SCF again correlated with the liver regeneration. We next treated mice with anti-SCF before sublethal doses of acetaminophen and significantly increased lethality in anti-SCF-treated animals. When exogenous SCF was given to mice, the lethality was significantly reduced compared with the control acetaminophen-treated animals and the damage within the liver tissue was attenuated. The administration of rSCF reduced the level of steady-state mRNA for cytochrome P450 cyp2E1 enzyme both in vitro and in vivo. These data suggest that SCF functions as an important factor that protects livers from acute damage.
Simpson
Kenneth
K
Department of Pathology, University of Edinburgh, Edinburgh, United Kingdom.
Hogaboam
Cory M
CM
Kunkel
Steven L
SL
Harrison
David J
DJ
Bone-Larson
Cindy
C
Lukacs
Nicholas W
NW
D000082:Acetaminophen; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D019138:Antibodies, Blocking; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D000082:Acetaminophen; D019392:Cytochrome P-450 CYP2E1