Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart

We examined whether antidiabetic drug miglitol could reduce ischaemia/reperfusion‐induced myocardial apoptosis by attenuating production. 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. 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. These data suggest that miglitol reduces myocardial apoptosis by attenuating production of hydroxyl radicals and suppressing the upregulation of the expression of Bax protein.British Journal of Pharmacology (2004) 142 , 983–990. doi: 10.1038/sj.bjp.0705863