Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces myocardial reperfusion injury in the rat.
We investigated the effects of pretreatment with interleukin (IL)-1 alpha on the expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion-induced arrhythmias and the size of myocardial infarct in rats. Male Wistar rats received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed that Mn-SOD mRNA was mainly expressed in the heart and slightly in kidney, but not in any other organs. The expression of Mn-SOD mRNA peaked at 6 h after the injection of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after injection. In the isolated heart model, the rats were pretreated with IL-1 alpha 24 h earlier and their hearts were perfused by the Langendorff method. After 20 min of ischemia which was induced by a ligation of a coronary artery, reperfusion-induced arrhythmias were observed. There were no significant differences in the incidence of ventricular arrhythmias between the IL-1 alpha pretreated and the untreated hearts. IL-1 alpha pretreatment significantly reduced the mean duration of the ventricular arrhythmias and also delayed the onset of arrhythmias. The effect of IL-1 alpha pretreatment was also investigated in a 30-min model of ischemia followed by a 3-min reperfusion in anesthetized rats. The infarct size expressed as a percentage of the area at risk was significantly reduced in the IL-1 alpha pretreated hearts compared with the untreated hearts. The left ventricular systolic pressure increased significantly in rat hearts pretreated with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1 alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also suggested that pretreatment with IL-1 alpha 24 h before ischemia reduced the risk of ischemia-reperfusion injury.
Nogae
C
C
Department of Bioclimatology and Medicine, Kyushu University, Beppu, Japan.
Makino
N
N
Hata
T
T
Nogae
I
I
Takahashi
S
S
Suzuki
K
K
Taniguchi
N
N
Yanaga
T
T
D000768:Anesthesia, General; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004790:Enzyme Induction / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008345:Manganese; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D007155:Immunologic Factors; D007375:Interleukin-1; D011994:Recombinant Proteins; D008345:Manganese; D013482:Superoxide Dismutase