Lipid Peroxidation Activates Mitogen-Activated Protein Kinases in Testicular Ischemia-Reperfusion Injury
| Autor: | Francesco Squadrito, Pietro Antonuccio, Carmelo Romeo, Alessandra Bitto, Letteria Minutoli, Francesca Polito, Biagio Zuccarello, Salvatore Arena, Domenica Altavilla, P. A. Nicotina |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Urology Ischemia Antioxidants Lipid peroxidation chemistry.chemical_compound Internal medicine medicine Animals Vitamin E Testicular torsion RNA Messenger mitogen-activated protein kinase testis torsion Extracellular Signal-Regulated MAP Kinases Protein kinase A Benzofurans Spermatic Cord Torsion biology Tumor Necrosis Factor-alpha business.industry Kinase JNK Mitogen-Activated Protein Kinases medicine.disease Rats Endocrinology chemistry Reperfusion Injury Mitogen-activated protein kinase biology.protein Lipid Peroxidation Signal transduction business Reperfusion injury |
| Zdroj: | Journal of Urology. 176:1666-1672 |
| ISSN: | 1527-3792 0022-5347 |
| DOI: | 10.1016/j.juro.2006.06.086 |
| Popis: | Testicular damage after torsion has been attributed to many mechanisms, of which one is lipid peroxidation of the plasma membrane, which could cause the activation of the mitogen-activated protein kinase family. These proteins are of vital importance for signal transduction pathways and 2 of them, extracellular signal-regulated kinase and c-jun N-terminal kinase, participate in the pathogenesis of testicular ischemia. We investigated whether lipid peroxidation may trigger mitogen-activated protein kinase activation in testicular ischemia-reperfusion.Adult male Sprague-Dawley rats were subjected to 1-hour testicular ischemia, followed by 24 hours of reperfusion. Sham testicular ischemia-reperfusion rats served as controls. Animals were randomized to receive raxofelast, an inhibitor of lipid peroxidation (20 mg/kg intraperitoneally administered 15 minutes before detorsion and 15 minutes after detorsion) or vehicle (1 ml/kg 10% dimethyl sulfoxide/NaCl solution). A group of animals was sacrificed 0, 10, 15, 20, 25 and 30 minutes, and 1, 2 and 3 hours, respectively, after detorsion to evaluate testicular c-jun N-terminal kinase, extracellular signal-regulated kinase and tumor necrosis factor-alpha activation by Western blot analysis, and mRNA expression and conjugated dienes using a spectrophotometer technique. Another group was sacrificed 24 hours after detorsion to evaluate histological alterations.Testicular ischemia-reperfusion injury caused a significant increase in the conjugated diene levels, extracellular signal-regulated kinase c-jun N-terminal kinase activity and tumor necrosis factor-alpha expression in both testes. Furthermore, histological examination revealed marked damage. Raxofelast inhibited these parameters and decreased histological damage.These data suggest that lipid peroxidation triggers extracellular signal-regulated kinase and c-jun N-terminal kinase activation. Furthermore, mitogen-activated protein kinase blockade might represent a potential therapeutic approach to treatment in patients with unilateral testicular torsion. |
| Databáze: | OpenAIRE |
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