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Titolo:
Role of protein kinase C, K-ATP channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970
Autore:
Hashimoto, K; Minatoguchi, S; Hashimoto, Y; Wang, NY; Qin, XB; Yamashita, K; Uno, Y; Arai, M; Nishida, Y; Takemura, G; Suzuki, T; Fujiwara, T; Fujiwara, H;
Indirizzi:
Gifu Univ, Sch Med, Dept Internal Med 2, Gifu 5008705, Japan Gifu Univ Gifu Japan 5008705 d, Dept Internal Med 2, Gifu 5008705, Japan Tanabe Seiyaku Co Ltd, Toda, Saitama, Japan Tanabe Seiyaku Co Ltd Toda Saitama Japan ku Co Ltd, Toda, Saitama, Japan Kyoto Womens Univ, Dept Food Sci, Kyoto, Japan Kyoto Womens Univ Kyoto Japan Womens Univ, Dept Food Sci, Kyoto, Japan
Titolo Testata:
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
fascicolo: 3, volume: 28, anno: 2001,
pagine: 193 - 199
SICI:
0305-1870(200103)28:3<193:ROPKCK>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
ISOLATED RABBIT HEART; SUPEROXIDE-DISMUTASE; MYOCARDIAL-ISCHEMIA; HYDROXYL RADICALS; REPERFUSION INJURY; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CELL-DEATH; IN-SITU; ACTIVATION;
Keywords:
DNA fragmentation; free radical scavenger; hydroxyl radicals; K-ATP channel; myocardial infarction; protein kinase C; rabbits; reperfusion injury; T-0970;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Fujiwara, H Gifu Univ, Sch Med, Dept Internal Med 2, 40 Tsukasa Machi, Gifu 5008705, Japan Gifu Univ 40 Tsukasa Machi Gifu Japan 5008705 5008705, Japan
Citazione:
K. Hashimoto et al., "Role of protein kinase C, K-ATP channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970", CLIN EXP PH, 28(3), 2001, pp. 193-199

Abstract

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 and48 h reperfusion. The central 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; 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 mug/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of proteinkinase 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. After48 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 myocyteswas 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<0.05). This reduction of infarct size by T-0970 was abolished by pretreatment with CHE and 5-HD. Neither CHE nor 5-HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T-0970 group was significantly reduced compared with the number in the control group (4.0+/-1.5 vs 10.7 +/- 1.9%, respectively; P < 0.05).5. T-0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K-ATP channels and inhibition of DNA fragmentation.

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Documento generato il 04/04/20 alle ore 08:25:37