Radical scavenging properties of novel benzopyran derivatives, TA248 and TA276, and effects of the compounds on ischemic/reperfused myocardium in dogs.
Characteristics of novel benzopyran derivatives, TA248 and TA276, and their effects on myocardial contraction in ischemic/reperfused hearts in dogs were examined. TA248 and TA276 inhibited NADPH-dependent lipid peroxidation induced by Fe(3+) in the rat brain homogenate. Both compounds reduced *O(2-) produced by xanthine-xanthine oxidase system in a dose-dependent manner. TA276 scavenged.OH generated by Fenton reaction in a dose-dependent manner. TA248 also inhibited the.OH production, but the effect was neither complete nor dose dependent. Myocardial contraction was assessed as segment shortening of the left ventricular wall in pentobarbital-anesthetized open-chest dogs. The segment shortening was decreased by the left anterior descending coronary artery ligation (ischemia) and returned by release of the ligated artery (reperfusion). The segment shortening did not recover fully during reperfusion. Either TA248 or TA276 injected 10 min before ischemia improved the recovery of myocardial contraction during reperfusion. Both compounds preserved the level of ATP in the 60-min reperfused myocardium. However, the level of lipid peroxides was not changed by TA248 and TA276. TA248 and TA276 may protect myocardium against ischemic/reperfusion insult, partly because of their free radical scavenging activity, but no significant change in myocardial lipid peroxide level was observed.
Kosugi
T
T
Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka, Otaru 047-0264, Japan.
Satoh
K
K
Yamamoto
A
A
Hoshi
K
K
Aoki
Y
Y
Takagaki
H
H
Ichihara
K
K
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D001578:Benzopyrans; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; C414784:TA248; C414783:TA276; D013481:Superoxides; D017665:Hydroxyl Radical