Preconditioning with tin-protoporphyrin IX attenuates ischemia/reperfusion injury in the rat kidney.
BACKGROUND
Heme oxygenase (HO)-1 is induced as a unique stress response and leads to a transient resistance against oxidative damage, including ischemia and reperfusion (I/R) injury. In the present study, we examined whether HO-1 induction may confer a protection against I/R injury in the rat kidney.


METHODS
Lewis rats were divided into four groups as follows: (1) vehicle group; (2) group treated with ferri-protoporphyrin IX (hemin), an inducer of HO; (3) group treated with low-dose tin-protoporphyrin IX (SnPP), an inhibitor of HO; and (4) group treated with high-dose SnPP. Renal warm ischemia for 60 minutes was performed 24 hours after each treatment.


RESULTS
At 24 hours after treatment, hemin induced a significant increase in renal HO activity, but failed to induce HO-1 protein synthesis. Although both low- and high-dose SnPP reduced HO activity, a marked HO-1 expression was observed only in the high-dose SnPP-treated kidney. Hemin exacerbated the renal function after reperfusion, while high-dose SnPP significantly suppressed the intercellular adhesion molecule (ICAM)-1 expression, the infiltration of ED-1-positive macrophages and the expression of activated caspase-3, which resulted in attenuation of apoptotic cell death and ameliorated I/R injury.


CONCLUSIONS
These results suggest that prior induction of HO-1 protein by high-dose SnPP may lead to anti-inflammatory and antiapoptotic effects on warm renal I/R injury independently of its enzyme activity, and that HO enzyme activation may not always act as an antioxidant, especially under I/R-induced oxidative stress.
Kaizu
Takashi
T
Department of Surgery, Research Institute for Artificial Organs, Transplantation & Gene Therapy, Sapporo Hokuyu Hospital, Sapporo, Japan.
Tamaki
Tohru
T
Tanaka
Mitsuko
M
Uchida
Yasushi
Y
Tsuchihashi
Sei-Ichiro
S
Kawamura
Akio
A
Kakita
Akira
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005293:Ferritins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019194:Ischemic Preconditioning; D007668:Kidney / Q000201:enzymology / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D018799:Intercellular Adhesion Molecule-1; D005293:Ferritins; D003404:Creatinine; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1