Linked Life Data

16125744

Source:http://linkedlifedata.com/resource/pubmed/id/16125744

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-2-20
pubmed:abstractText
Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate beta-lyase, the enzyme that bio-activates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephro-protection. These findings suggest that pre-placement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
211
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-47
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16125744-Animals, pubmed-meshheading:16125744-Area Under Curve, pubmed-meshheading:16125744-Blood Urea Nitrogen, pubmed-meshheading:16125744-Bromodeoxyuridine, pubmed-meshheading:16125744-Cell Nucleus, pubmed-meshheading:16125744-Colchicine, pubmed-meshheading:16125744-Creatinine, pubmed-meshheading:16125744-Cysteine, pubmed-meshheading:16125744-Diabetes Mellitus, Experimental, pubmed-meshheading:16125744-Diabetic Nephropathies, pubmed-meshheading:16125744-Dose-Response Relationship, Drug, pubmed-meshheading:16125744-Half-Life, pubmed-meshheading:16125744-Immunohistochemistry, pubmed-meshheading:16125744-Injections, Intraperitoneal, pubmed-meshheading:16125744-Kidney Tubules, Proximal, pubmed-meshheading:16125744-Lyases, pubmed-meshheading:16125744-Male, pubmed-meshheading:16125744-Mice, pubmed-meshheading:16125744-Proliferating Cell Nuclear Antigen, pubmed-meshheading:16125744-Regeneration, pubmed-meshheading:16125744-S Phase, pubmed-meshheading:16125744-Streptozocin, pubmed-meshheading:16125744-Thymidine, pubmed-meshheading:16125744-Tritium
pubmed:year
2006
pubmed:articleTitle
Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair.
pubmed:affiliation
Department of Toxicology, College of Pharmacy, The University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209-0470, USA.
pubmed:publicationType
Journal Article, Comparative Study