Different role of antioxidants in endotoxin-induced late myocardial protection.
Previous studies have proposed that endogenous antioxidants play a protective role against cardiac ischemia-reperfusion injury in endotoxin pretreatment. However, the mechanism underlying this effect remains elusive. We therefore evaluated the role of endogenous antioxidants in delayed myocardial protection after different doses of endotoxin administration using cultured rat neonatal cardiomyocytes. Myocytes were treated with normal saline (control) or lipopolysaccharide (Escherichia coli, serotype O111) at doses of 40 and 80 microg/ml (ET40 and ET80). Also, antisense oligodeoxyribonucleotide (1.5 micromol/L) to manganese superoxide dismutase (Mn-SOD) and 3-amino-1,2,4-triazole (25 mg/ml) were added along with a 40 or 80 microg/ml endotoxin pretreatment in the IET40 and IET80 groups. Twenty-four hours later, Cells were subjected to hypoxia (pO2 < 1 kPa, 3 h) and reoxygenation (pO2: 19 kPa, 1 h). Compared with controls, cell viability enhanced significantly (65.3 +/- 5.9, 63.8 +/- 4.6, and 69.7 +/- 5.2% vs 47.2 +/- 4.3%, P < 0.05) and creatine kinase release decreased (7.34 +/- 1.76, 7.11 +/- 1.49, and 6.27 +/- 1.24 U/mg protein vs 11.23 +/- 2.49 U/mg protein, P < 0. 05) in ET40, IET40, and ET80 groups following reoxygenation. No statistically significant difference was found between the control and the IET80 groups. Furthermore, the levels of Mn-SOD (1.12 +/- 0. 31 vs 0.75 +/- 0.15 U/mg. protein, P < 0.05) and catalase activity (1265 +/- 109 vs 996 +/- 85 U/mg. protein, P < 0.05) were higher only in the ET80 group. The results suggest that at a dose of 40 microg/ml, cells were protected by mechanisms other than the augmentation of endogenous antioxidant activity which were more evident at a dose of 80 microg/ml. It seems that different doses of endotoxin pretreatment may induce delayed myocardial protection through various mechanisms.
Wang
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S
Gan Quan Hospital, Shanghai Tiedao University, Shanghai, People's Republic of China. wanson@online.sh.cn
Zhu
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Xie
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Chen
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C
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D000860:Hypoxia / Q000201:enzymology / Q000473:pathology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D004731:Endotoxins; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D010100:Oxygen