Role of protein kinase C, K(ATP) channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970
| Autor: | Yasuko Hashimoto, Hisayoshi Fujiwara, Toshikazu Suzuki, Yoshio Nishida, Shinya Minatoguchi, Takako Fujiwara, Masazumi Arai, Genzou Takemura, Ningyuan Wang, Kazuaki Hashimoto, Yoshihiro Uno, Xinbin Qiu, Kazuya Yamashita |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Microdialysis Potassium Channels Physiology Pyridines Myocardial Infarction Myocardial Reperfusion Injury DNA Fragmentation Pharmacology Antioxidants chemistry.chemical_compound KATP Channels In vivo Physiology (medical) medicine In Situ Nick-End Labeling Animals Potassium Channels Inwardly Rectifying Protein Kinase C TUNEL assay Chemistry Hydroxyl Radical Myocardium Phenylurea Compounds Hemodynamics medicine.disease Free radical scavenger Enzyme Activation Chelerythrine Coronary occlusion Anesthesia DNA fragmentation ATP-Binding Cassette Transporters Rabbits Reperfusion injury |
| Zdroj: | Clinical and experimental pharmacologyphysiology. 28(3) |
| ISSN: | 0305-1870 |
| Popis: | 1. In the present study, we investigated the effect of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl) urea hydrocloride (T-0970), a novel water-soluble low-molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T-0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T-0970 group; n = 10) was injected with a bolus 2.5 mg/kg T-0970 and then infused with T-0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 microg/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T-0970. The T-0970 + 5-HD group (n = 5) was given 5-hydroxydecanoate (5-HD; an inhibitor of mitochondrial K(ATP) channels; 5 mg/kg, i.v.) 10 min before the administration of T-0970. The CHE and 5-HD groups were given CHE (5 mg/kg, i.v.) and 5-HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control (n = 5) and T-0970 (n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end-labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T-0970 group was significantly reduced compared with the control group (21+/-4 vs 41+/-4%, respectively; P |
| Databáze: | OpenAIRE |
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