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Target Concepts:
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Query: UMLS:C0022672 (
acute tubular necrosis
)
2,175
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
S-(1,2-Dichlorovinyl)-L-cysteine
(
DCVC
), a model nephrotoxicant in mice, causes
acute tubular necrosis
and death at high doses. Our earlier studies revealed that renal tissue repair was critical for survival in mice with
DCVC
nephrotoxicity. The objective of this study was to investigate if increasing renal tissue repair could protect mice from the lethal outcome of
DCVC
. Male Swiss Webster (SW) mice were administered a low dose of
DCVC
(15 mg/kg, ip) 72 h before injection of a normally lethal dose of
DCVC
(75 mg/kg, ip); this resulted in 100% protection against the lethal effect of
DCVC
. Because
DCVC
caused approximately two fold decrease in cytosolic and mitochondrial beta-lyase activity, the possibility that
DCVC
protection may be caused by decreased bioactivation was examined. Mercuric chloride (HgCl2, 6 mg/kg), a nephrotoxicant with no effect on beta-lyase activity, was administered 96 h before a lethal dose of
DCVC
. This also resulted in 100% protection from the lethal effect of
DCVC
. In both studies total glutathione was unchanged at any time after the lethal dose of
DCVC
was administered, obviating the role of glutathione in protection. In both cases the augmented and sustained tissue repair induced by priming dose and documented by 3H-thymidine pulse labeling and immunocytochemistry for proliferating cell nuclear antigen resulted in 100% survival in spite of the extensive renal injury. These findings suggest that stimulation of renal tubular repair by the priming dose, through augmented cell division, and the resistance of new cells to mechanisms of progression of injury, underlies auto- and heteroprotection against
DCVC
. The molecular mechanisms may have potential application in pharmacotherapeutic intervention for treatment of acute renal failure.
...
PMID:Role of tissue repair in survival from s-(1,2-dichlorovinyl)-L-cysteine-induced acute renal tubular necrosis in the mouse. 1273 Jun 12
