Spaciotemporal Alteration of 8-hydroxy-2′-deoxyguanosine Levels in Cardiomyocytes After Myocardial Infarction in Rats

Abstract

Temporary or persistent heart failure is one of the major complications after myocardial infarction (MI). In order to elucidate the pathogenesis of MI, we studied the spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in cardiomyocytes in a rat model of ligation of the left anterior descending branch of the coronary artery. The lethality in this model was 18%. Hearts were dissected at 0, 3, 6, 12, 24, 48 h, and 1, 2, 4, 6 weeks after the operation. The cardiac level of 8-OHdG was evaluated biochemically as well as by immunohistochemistry with monoclonal antibody N45.1. Three to 6h after ligation, the 8-OHdG levels were increased in the cardiomyocytes of MI (six-fold) and peri-MI (four-fold) areas. After 24 h, the myocardium in the MI area was necrotized, and thereafter the 8-OHdG level decreased. 8-OHdG levels in the myocardium of peri-MI areas returned once to a normal level, but were significantly increased at 2-4 weeks along with the appearance of apoptotic cardiomyocytes in this area. The heart after MI has been generally considered as clinically stable after four weeks. However, cardiomyocytes near the infarcted area were oxidatively stressed even after four weeks when the affected lesion was extensive. The present data support the use of supplementary antioxidant therapies to save functional myocardium after MI. (213 words)

Elevated Levels of Oxidative DNA Damage in Serum and Myocardium of Patients With Heart Failure

“…In fact, increased oxidative DNA damage has been shown at 2-4 weeks after myocardial infarction, together with apoptotic cardiomyocytes in the peri-infarct areas. 32 The serum 8-OHdG levels were elevated in patients with DCM, but did not correlate with LVDd or LVEF in this study. The serum 8-OHdG levels are affected by oxidative stress not only in heart but systemically.…”

Oxidative and Antioxidative Status after Successful Percutaneous Transluminal Coronary Angioplasty in Acute Myocardial Infarction

“…Reperfusion achieved by PTCA causes an increase in the activity of DNA repair enzymes. In rat studies 8-hydroxydeoxyguanosine levels were found to increase in infracted regions [10]. Nagayoshi Y, et al [11] showed that in patients with acute myocardial infarction, 8-OHdG levels were high at the beginning, reached their peak at the fourth hour after reperfusion and started to decrease at the 24 th hour.…”

Protective effect of cardioplegia with poly (ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury: in vitro study of isolated rat heart model

“…Ischemia reduces the activity of cellular defense enzymes against free radicals 15 , and reperfusion, or introduction of oxygen, further disturbs the balance between oxidants and antioxidants and generates a burst of free radicals in the tissue. We showed by using immunohistochemistry that the level of 8-OHdG, that is a major product of oxidative DNA modifications, increased in cardiomyocytes after myocardial infarction 16 . By calculating the 8-OHdG index, we demonstrated that 3-AB had an ability to protect DNA against oxidative stress in our previous study 11 , and also 4-HQ has the same ability of protection in this study.…”