Preconditioning with tin-protoporphyrin IX attenuates ischemia/reperfusion injury in the rat kidney
| Autor: | Yasushi Uchida, Akira Kakita, Akio Kawamura, Takashi Kaizu, Tohru Tamaki, Seiichiro Tsuchihashi, Mitsuko Tanaka |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Pathology medicine.medical_specialty Metalloporphyrins Ischemia Protoporphyrins Apoptosis Pharmacology Kidney medicine.disease_cause tin-protoporphyrin IX chemistry.chemical_compound medicine Animals HSP70 Heat-Shock Proteins Enzyme Inhibitors Enzyme inducer Ischemic Preconditioning biology business.industry Macrophages Intercellular Adhesion Molecule-1 medicine.disease ischemia and reperfusion injury Immunohistochemistry Rats Heme oxygenase medicine.anatomical_structure chemistry Rats Inbred Lew Nephrology Creatinine Enzyme Induction Reperfusion Injury Ferritins Heme Oxygenase (Decyclizing) biology.protein Ischemic preconditioning business Reperfusion injury Heme Oxygenase-1 Oxidative stress Hemin |
| Zdroj: | Kidney International. 63:1393-1403 |
| ISSN: | 0085-2538 |
| Popis: | 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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