title: Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart.
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.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa Machi, Gifu 500, Japan.
authors.forename: Ningyuan
authors.initials: N
authors.lastname: Wang
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Xuehai
authors.initials: X
authors.lastname: Chen
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.forename: ChuanJiang
authors.initials: C
authors.lastname: Lu
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005841:Gentisates / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017665:Hydroxyl Radical / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050112:Imino Pyranoses; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D005841:Gentisates; D007004:Hypoglycemic Agents; D050112:Imino Pyranoses; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C045621:miglitol; D017485:1-Deoxynojirimycin; D017665:Hydroxyl Radical; D005944:Glucosamine; C010925:2,5-dihydroxybenzoic acid