Bimoclomol ameliorates mercuric chloride nephrotoxicity through recruitment of stress proteins.
Bimoclomol (BIM), is a stress proteins coinducer, that acts synergistically with a mild stressor to activate cytoprotective stress proteins. BIM has been successfully utilized in animal models for the treatment of various nervous, cardiac and cerebrovascular diseases. Mercuric chloride (HgCl(2)) induces acute renal failure in rats by a single dosage. The present in vivo study was conducted to assess the efficacy of BIM against acute HgCl(2) nephrotoxicity. At different times after BIM and/or HgCl(2) exposure we evaluated renal morphology and the localization/abundance of three stress proteins (HSP72, GRP75, HSP60) by electron microscopy, immunohistochemistry and Western blot analysis. BIM delivery to rats 6h before mercury, ameliorated damage to renal ultrastructure, with recovery of tubular and mitochondrial membranes 24h after mercury treatment. In rats pretreated with BIM prior to HgCl(2) exposure, HSP72 was significantly overexpressed in proximal tubules in a time-dependent manner. In contrast, the amounts of GRP75 and HSP60 after BIM pretreatment were comparable to the group treated with mercury alone, but these stress proteins had translocated to the nuclei at 14 and 24h, respectively. These novel findings suggest that BIM mitigates HgCl(2) nephrotoxicity in rats through the early recruitment of stress proteins in midcortical proximal tubules that are the main renal mercury-targets.
Stacchiotti
Alessandra
A
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, I 25123 Brescia, Italy. stacchio@med.unibs.it
Borsani
Elisa
E
Ricci
Francesca
F
Lavazza
Antonio
A
Rezzani
Rita
R
Bianchi
Rossella
R
Rodella
Luigi Fabrizio
LF
D000818:Animals; D015153:Blotting, Western; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007094:Imides / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006360:Heat-Shock Proteins; D007094:Imides; D011725:Pyridines; D008627:Mercuric Chloride; C108730:bimoclomol