The effects of ubidecarenone derivatives on the action of phospholipase.
Anti-phospholipase (Plase) action of ubidecarenone (coenzyme Q10, CoQ10, E-0216) derivatives was investigated. CoQ10 and its derivatives prevented the release of fatty acids from canine heart mitochondrial phopholipids induced by PLase A2 and PLase C. The protective effects of the carboxyl derivatives of CoQ10 of the benzoquinone type (BQs) and of the methoxyl type (MPs) were stronger than that of CoQ10. MPs with 3 isoprenoid units (MP-3) was more effective than BQs with 3 isoprenoid units (BQ-3) with respect to PLase A2, while they showed similar protective effect against PLase C attack. The effects of BQ-3 and MP-3 on reperfusion arrhythmias were investigated in anesthetized dogs. Dogs were divided into three groups: the control group (n = 38), the BQ-3 group (n = 11), and the MP-3 group (n = 11). Physiological saline or 5 mg/kg of BQ-3 or MP-3 was premedicated in each group. 20 min after premedication, the left anterior descending coronary artery was occluded for 15 min followed by 5 min reperfusion. 32% of the controls developed reperfusion arrhythmias, while none of the dogs pretreated with CoQ10 derivatives developed arrhythmias. Immediately after 5 min of reperfusion, heart microsomes were prepared from normal and reperfused areas and the PLase activity in microsomes was measured by high performance liquid chromatography. In the arrhythmias cases of the control group, the endogenous PLase activity obtained from reperfused myocardium increased significantly compared with that from normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000201:enzymology*; D003067:Coenzymes; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008861:Microsomes / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D003067:Coenzymes; D005230:Fatty Acids, Nonesterified; D014451:Ubiquinone; D010740:Phospholipases; C024989:coenzyme Q10; C025204:Ubiquinone Q2