Literature DB >> 15296883

Peroxynitrite, a product between nitric oxide and superoxide anion, plays a cytotoxic role in the development of post-bypass systemic inflammatory response.

Yoshitaka Hayashi1, Yoshiki Sawa, Motonobu Nishimura, Naoto Fukuyama, Hajime Ichikawa, Shigeaki Ohtake, Hiroe Nakazawa, Hikaru Matsuda.   

Abstract

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to induce post-bypass systemic inflammatory response. Peroxynitrite (ONOO-) is a potent oxidant formed by a rapid reaction between nitric oxide (NO) and superoxide anion. We hypothesized that ONOO- plays a role in the development of post-bypass systemic inflammatory response and examined the efficacy of ONOO- scavenger in a rat-CPB model.
METHODS: Adult Sprague-Dawley rats underwent 60 min of CPB (100 ml/kg per min, 34 degrees C). Group-P (n = 10) received 50 mg/kg of ONOO- scavenger, quercetin, intraperitoneally 24 h before the initiation of CPB, and Group-C (n = 10) served as controls.
RESULTS: There were significant time-dependent changes in plasma nitrate+nitrite (NOx), the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr: an indicator of ONOO- formation), interleukin (IL)-6, IL-8, and respiratory index (RI). There were significant differences in %NO2-Tyr between the groups both at CPB termination (Group-P vs C; 0.26+/-0.07 vs 0.55+/-0.11%, P < 0.01) and 3 h after CPB termination (0.65+/-0.14 vs 1.46+/-0.25%, P < 0.01); whereas there were no significant differences in NOx between the groups at any sampling point ((at CPB termination) Group-P vs C; 31.6+/-4.3 vs 32.7+/-4.1 micromol/l, (3 h after CPB termination) Group-P vs C; 47.8+/-4.9 vs 51.7+/-5.3 micromol/l). Group-P showed significantly lower plasma IL-6 (176.8+/-44.3 vs 302.4+/-78.1 pg/ml, P < 0.01), IL-8 (9.45+/-1.78 vs 16.42+/-2.53 ng/ml, P < 0.01) and RI (1.07+/-0.19 vs 1.54+/-0.25, P < 0.01) 3 h after CPB termination, though there were no significant differences between the groups at CPB termination.
CONCLUSIONS: These results suggest that ONOO- plays a crucial role in the development of post-bypass systemic inflammatory response and the pretreatment with quercetin has a potential benefit to avoid deleterious effects of ONOO-.

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Year:  2004        PMID: 15296883     DOI: 10.1016/j.ejcts.2004.03.033

Source DB:  PubMed          Journal:  Eur J Cardiothorac Surg        ISSN: 1010-7940            Impact factor:   4.191


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