Tin chloride pretreatment prevents renal injury in rats with ischemic acute renal failure.
OBJECTIVE
To investigate whether tin chloride pretreatment ameliorates renal injury in rats with ischemic acute renal failure (IARF) by virtue of its kidney-specific heme oxygenase-1 induction.


METHODS
Randomized, masked, controlled animal study.


METHODS
University-based animal research facility.


METHODS
Sprague-Dawley male rats, weighing 200-230 g (n = 359).


METHODS
Rats were injected with tin chloride subcutaneously, because subcutaneous administration of tin chloride is known to specifically and potently induce renal heme oxygenase activity in the rat. Anesthetized rats were subjected to bilateral flank incisions, and the right kidney was removed. Renal ischemia for 40 mins was performed by left renal microvascular clamping, followed by reflow of the blood.


RESULTS
Tin chloride treatment specifically induced heme oxygenase-1 mRNA and protein in the proximal tubular epithelial cells of the kidney without apparent cell injury in the rat. Tin chloride treatment before renal ischemia augmented the induction of heme oxygenase-1 in IARF rats at both transcriptional and protein concentrations in the renal epithelial cells compared with IARF animals. Tin chloride pretreatment, which decreased microsomal heme concentration, ameliorated the ischemic renal injury as judged by the significant decrease in serum creatinine and blood urea nitrogen concentrations and the lesser tubular epithelial cell injuries. In contrast, inhibition of heme oxygenase activity by treatment with tin mesoporphyrin, which increased microsomal heme concentration, abolished the beneficial effect of tin chloride pretreatment.


CONCLUSIONS
These findings indicate that tin chloride pretreatment significantly ameliorates renal injury in rats with IARF by virtue of its specific heme oxygenase-1 induction in renal epithelial cells. These findings also suggest that heme oxygenase-1 induction plays an important role in protecting renal cells from oxidative damage caused by heme.
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, Japan.
Narushi
N
Toda
Toru
T
Takahashi
Satoshi
S
Mizobuchi
Hiromi
H
Fujii
Kiichi
K
Nakahira
Shuji
S
Takahashi
Masami
M
Yamashita
Kiyoshi
K
Morita
Masahisa
M
Hirakawa
Reiko
R
Akagi
D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D007511:Ischemia / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D017971:Tin Compounds / Q000627:therapeutic use*
D017971:Tin Compounds; C023599:stannous chloride