Linked Life Data

13678654

Source:http://linkedlifedata.com/resource/pubmed/id/13678654

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-9-18
pubmed:abstractText
Liver injury is known to progress even after the hepatotoxicant is long gone and the mechanisms of progressive injury are not understood. We tested the hypothesis that hydrolytic enzymes such as calpain, released from dying hepatocytes, destroy the surrounding cells causing progression of injury. Calpain inhibitor, N-CBZ-VAL-PHE-methyl ester (CBZ), administered 1 h after a toxic but nonlethal dose of CCl(4) (2 ml/kg, ip) to male Sprague Dawley rats substantially mitigated the progression of liver injury (6 to 48 h) and also led to 75% protection against CCl(4)-induced lethality following a lethal dose (LD75) of CCl(4) (3 ml/kg). Calpain leakage in plasma and in the perinecrotic areas increased until 48 h and decreased from 72 h onward paralleling progression and regression of liver injury, respectively, after CCl(4) treatment. Mitigation of progressive injury was accompanied by substantially low calpain in perinecrotic areas and in plasma after CBZ treatment. Normal hepatocytes incubated with the plasma collected from CCl(4)-treated rats (collected at 12 h when most of the CCl(4) is eliminated) resulted in extensive cell death prevented by CBZ. Cell-impermeable calpain inhibitor E64 also protected against progression of CCl(4)-induced liver injury, thereby confirming the role of released calpain in progression of liver injury. Following CCl(4) treatment, calpain-specific breakdown of alpha-fodrin increased, while it was negligible in rats receiving CBZ after CCl(4). Hepatocyte cell death in incubations containing calpain was completely prevented by CBZ. Eighty percent of Swiss Webster mice receiving a lethal dose (LD80) of acetaminophen (600 mg/kg, ip) survived if CBZ was administered 1 h after acetaminophen, suggesting that calpain-mediated progression of liver injury is neither species nor chemical specific. These findings suggest the role of calpain in progression of liver injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
191
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
211-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:13678654-Acetaminophen, pubmed-meshheading:13678654-Animals, pubmed-meshheading:13678654-Blotting, Western, pubmed-meshheading:13678654-Calpain, pubmed-meshheading:13678654-Carbon Tetrachloride, pubmed-meshheading:13678654-Carrier Proteins, pubmed-meshheading:13678654-Cysteine Proteinase Inhibitors, pubmed-meshheading:13678654-Cytochrome P-450 CYP2E1, pubmed-meshheading:13678654-Dipeptides, pubmed-meshheading:13678654-Disease Progression, pubmed-meshheading:13678654-Drug-Induced Liver Injury, pubmed-meshheading:13678654-Hepatocytes, pubmed-meshheading:13678654-Immunohistochemistry, pubmed-meshheading:13678654-Liver Diseases, pubmed-meshheading:13678654-Male, pubmed-meshheading:13678654-Mice, pubmed-meshheading:13678654-Microfilament Proteins, pubmed-meshheading:13678654-Necrosis, pubmed-meshheading:13678654-Random Allocation, pubmed-meshheading:13678654-Rats, pubmed-meshheading:13678654-Rats, Sprague-Dawley
pubmed:year
2003
pubmed:articleTitle
Calpain released from dying hepatocytes mediates progression of acute liver injury induced by model hepatotoxicants.
pubmed:affiliation
College of Health Sciences, The University of Louisiana at Monroe, Monroe, LA 71209, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't