Abstract
1 We examined whether antidiabetic drug miglitol could reduce ischaemia/reperfusion-induced myocardial apoptosis by attenuating production. 2 Japanese white rabbits were subjected to 30-min coronary occlusion followed by 4-h reperfusion with miglitol (10 mg kg(-1), i.v., n=20) or saline (n=20). The infarct area was determined by myoglobin staining, and the infarct size (IS) was expressed as a percentage of the area at risk. DNA fragmentation was assessed by TUNEL method and DNA ladder formation. The expression of Bcl-XL and Bax was detected by immunohistochemical analysis and Western blot analysis. Myocardial interstitial 2,5-DHBA levels, an indicator of hydroxyl radicals, were measured during 30-min ischaemia and 30-min reperfusion in the absence (n=10) or presence of miglitol (10 mg kg(-1), i.v., n=10) using a microdialysis technique. 3 The IS was significantly reduced in the miglitol group (22.4+/-3.4%, n=10) compared to the control group (52.8+/-3.5%, n=10). Miglitol significantly decreased the 2,5-DHBA level during ischaemia and reperfusion and suppressed the incidence of TUNEL-positive myocytes in the ischaemic region (from 10.7+/-3.4 to 4.1+/-3.0%) and the intensity of DNA ladder formation. Miglitol significantly decreased the incidence of Bax-positive myocytes in the ischaemic region (7.4+/-1.7 vs 13.7+/-1.9% of the control) and significantly attenuated the upregulation of Bax protein in the ischaemic regions (from 179+/-17 to 90+/-12% of sham). There was no difference in the expression of Bcl-XL between the two groups. 4 These data suggest that miglitol reduces myocardial apoptosis by attenuating production of hydroxyl radicals and suppressing the upregulation of the expression of Bax protein.