Protective effect of TMG, a novel vitamin E derivative, on myocardial ischemia-reperfusion injury

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.118-118
• Main Authors: Okabe, Eiichiro, Todoki, Kazuo, Shoji, Hirofumi, Takahashi, Shun-suke, Murase, Hironobu, Yoshikawa, Toshikazu
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)47938-9

A novel vitamin E derivative, 2-(α-D-glucopyranosyl)methyl-2,5,7,8-tetraniethychronsan-6-ol (TMG), has excellent water-solubility (>1×10^3 mg/ml). We studied the effect of TMG on total ischemia- reperfusion (I/R) injury in isolated perfused rat hearts. The efficacies of various reactive oxygen species (ROS) scavengers were also investigated. In I/R hearts, the contractile function and coronary flow were reduced;reperfusion with histidine or a cocktail of superexide dismutase (SOD)-catalase (Cat)-mannitol (Man) resulted in significant protection against the effect of I/R. The incidence of arrhythniias during reperfusion was 100% in I/R hearts;the duration of arrhythmias was shortened with histidine or with SOD-Cat-Man. The decreased duration of normal sinus rhythm in I/R hearts was also protected with histidine or SOD-Cat-Man. TMG (1-10 μM) protected the observed I/R-induced changes in contractile function by pre-ischemic treatment (for 5 min) in a dosedependent fashion;post-ischemic treatment with TMG (10 μM for 10 min) was also effective. TMG (10 μM) mimicked the protective effects of ROS scavengers by pre- and post-ischemic treatments. ROS scavenging effect of TMG was assessed by electron spin resonance spectroscopy by use of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). We found that Fentons reagent (H_2 O_2 /FeSO_4 ) formed hydroxyl radical-DMPO spin adduct, which was effectively blunted by TMG. Further, H_2 O_2 -induced luminol-chemiluminescence was completely inhibited by TMG (1 μM);the observed effect was comparable to the effect of 200 units Cat. The findings show that the protective effect of TMG against myocardial I/R injury is due to its ability to scavenge ROS, possibly H_2 O_2 .