PMID- 22739141
OWN - NLM
STAT- MEDLINE
DCOM- 20121018
LR  - 20211021
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 92
IP  - 2
DP  - 2012 Aug
TI  - The effects of heparins on the liver: application of mechanistic serum biomarkers 
      in a randomized study in healthy volunteers.
PG  - 214-20
LID - 10.1038/clpt.2012.40 [doi]
AB  - Heparins have been reported to cause elevations in serum alanine aminotransferase 
      (ALT) and aspartate aminotransferase (AST) but have not been associated with 
      clinically significant liver injury. The mechanisms underlying these benign 
      laboratory abnormalities are unknown. Forty-eight healthy men were randomized to 
      receive subcutaneous injections of unfractionated heparin (UFH; 150 U/kg), 
      enoxaparin sodium (1 mg/kg), dalteparin sodium (120 IU/kg), or adomiparin sodium 
      (125 IU/kg; a novel heparin) every 12 h for 4.5 days. Asymptomatic elevations in 
      serum ALT or AST were observed in >90% of the subjects. Elevations were also 
      observed in the levels of serum sorbitol dehydrogenase (SDH), glutamate 
      dehydrogenase (GLDH), miR-122, high-mobility group box-1 protein (including the 
      acetylated form), full-length keratin 18, and DNA. Keratin 18 fragments, which 
      are apoptosis biomarkers, were not detected. Biomarker profiles did not differ 
      significantly across heparin treatments. We conclude that heparins as a class 
      cause self-limited and mild hepatocyte necrosis with secondary activation of an 
      innate immune response.
FAU - Harrill, A H
AU  - Harrill AH
AD  - Hamner-University of North Carolina Institute for Drug Safety Sciences, The 
      Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA.
FAU - Roach, J
AU  - Roach J
FAU - Fier, I
AU  - Fier I
FAU - Eaddy, J S
AU  - Eaddy JS
FAU - Kurtz, C L
AU  - Kurtz CL
FAU - Antoine, D J
AU  - Antoine DJ
FAU - Spencer, D M
AU  - Spencer DM
FAU - Kishimoto, T K
AU  - Kishimoto TK
FAU - Pisetsky, D S
AU  - Pisetsky DS
FAU - Park, B K
AU  - Park BK
FAU - Watkins, P B
AU  - Watkins PB
LA  - eng
GR  - G0700654/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120627
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Anticoagulants)
RN  - 0 (Biomarkers)
RN  - 0 (Enoxaparin)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Keratin-18)
RN  - 0 (MIRN122 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 9005-49-6 (Heparin)
RN  - EC 1.1.1.14 (L-Iditol 2-Dehydrogenase)
RN  - EC 1.4.1.2 (Glutamate Dehydrogenase)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Adult
MH  - Alanine Transaminase/blood
MH  - Anticoagulants/*pharmacokinetics/pharmacology
MH  - Aspartate Aminotransferases/blood
MH  - Biomarkers/*blood
MH  - Dalteparin/pharmacology
MH  - Enoxaparin/pharmacology
MH  - Glutamate Dehydrogenase/blood
MH  - HMGB1 Protein/blood
MH  - Heparin/pharmacokinetics/*pharmacology
MH  - Humans
MH  - Keratin-18/blood
MH  - L-Iditol 2-Dehydrogenase/blood
MH  - Liver/*drug effects
MH  - Male
MH  - MicroRNAs/blood
MH  - Middle Aged
MH  - Young Adult
PMC - PMC4320779
EDAT- 2012/06/29 06:00
MHDA- 2012/10/19 06:00
CRDT- 2012/06/29 06:00
PHST- 2012/06/29 06:00 [entrez]
PHST- 2012/06/29 06:00 [pubmed]
PHST- 2012/10/19 06:00 [medline]
AID - clpt201240 [pii]
AID - 10.1038/clpt.2012.40 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2012 Aug;92(2):214-20. doi: 10.1038/clpt.2012.40. Epub 2012 
      Jun 27.