Renal immunolocalization of kallikrein in cisplatin nephrotoxicity in rats.
Treatment of rats with cisplatin (4 mg kg-1 body wt i.p. injection) induced variations of urinary kallikrein excretion (UKE). Three phases were observed: a transient increase of UKE one day after injection, followed by a decrease up to 10 days suggesting an altered biosynthesis and a recovery phase with return to normal control values, 21 days after injection. Early morphological lesions were observed in proximal tubule cells on day 1; severe changes and tubular necrosis were observed in the following days. Less marked changes were also present in distal tubules but the vacuolated and desquamated cells appeared in the lumen of the tubules. By immunocytochemical methods, kallikrein was observed in connecting tubule cells, but also in some proximal tubule cells and along the endothelial side of the glomerular basement membrane and urinary space of glomeruli. An intense labelling was present in desquamated epithelial cells in dilated lumen of tubules. This study provides evidence of the presence of immunoreactive kallikrein in the glomerulus, already reported during acute failure, and confirms the use of urinary kallikrein measurements as a useful non-invasive index to assess a possible nephrotoxic effect at the distal level.
Orfila
C
C
INSERM CJF 91-07, CHU Ranguiel, Toulouse, France.
Bompart
G
G
Lepert
J C
JC
Suc
J M
JM
Girolami
J P
JP
D000818:Animals; D001485:Basement Membrane / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007610:Kallikreins / Q000032:analysis* / Q000652:urine; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000737:chemistry* / Q000187:drug effects / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016707:Tissue Fixation
D007610:Kallikreins; D002945:Cisplatin