3-O-alkylascorbic acids as free radical quenchers. 3. Protective effect on coronary occlusion-reperfusion induced arrhythmias in anesthetized rats.
Structural modification of ascorbic acid by substitution of the 3-hydroxy group with lipophilic moieties has allowed the development of agents for treating reperfusion injury. These ascorbic acid derivatives inhibited lipid peroxidation, and some of them also reduced coronary reperfusion-induced arrhythmias in anesthetized rats. We found that 3-O-[(dodecylcarbonyl)methyl]ascorbic acid (8) was protective against reperfusion injury without directly influencing hemodynamics. 2-O-Octadecylascorbic acid (19) and 5,6-O-dodecylideneascorbic acid (15) also exhibited a marked effect on reperfusion injury, but significantly reduced the arterial blood pressure and heart rate in rats.
Nihro
Y
Y
Faculty of Pharmaceutical Science, Tokushima Bunri University, Japan.
Sogawa
S
S
Izumi
A
A
Sasamori
A
A
Sudo
T
T
Miki
T
T
Matsumoto
H
H
Satoh
T
T
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016166:Free Radical Scavengers; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D016166:Free Radical Scavengers; D014700:Verapamil; D001205:Ascorbic Acid