Disease relevance of CCRIS 4543

• These results indicate that CV 3611, which has been proved to pass through the cell membrane and to have a long half life in plasma and tissue, had an important therapeutic effect on the development of acute pancreatitis [1].
• Thus, CV-3611 clearly suppressed the development of hepatocellular carcinomas [2].
• The proteinuria was also not reduced by administration of an AOS scavenger, 2-O-octadecylascorbic acid (4, CV-3611) [3].
• The free radical scavenger CV-3611 significantly attenuated a decrease in body weight and renal dysfunction without reducing tubular damage [4].
• Effects of pretreatment with 2-O-octadecylascorbic acid, a novel free radical scavenger, on reperfusion-induced arrhythmias in isolated perfused rat hearts [5].

High impact information on CCRIS 4543

• 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 [6].
• 2-O-Octadecylascorbic acid (5k, CV-3611), one of the most potent and promising compounds, markedly inhibited lipid peroxidation (IC50 = 4.3 X 10(-6) M) and alleviated myocardial lesions induced by ischemia-reperfusion at an oral dose of 1 mg/kg in rats [7].
• CV-3611 also reduced the number of aggregates of bladder epithelial cells from rats treated with BHBN for 4 weeks [8].
• Treatment with CV-3611 reduced the effects of the bladder tumor promoters sodium saccharin and DL-tryptophan by 48-86 and 65-87%, respectively [8].
• Mice were divided into three groups: control group, intraperitoneal injection of saline only; pancreatitis group, cerulein 50 micrograms/kg injected intraperitoneally six times at 1-hr intervals; treatment groups, CV-3611 10 mg/kg subcutaneously just after intraperitoneal cerulein injection [9].

Chemical compound and disease context of CCRIS 4543

• Suppression of spontaneous hepatocellular carcinoma development in C3H/HeNCrj mice by the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611) [2].
• Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity [10].
• However, in severe acute pancreatitis characterized by death occurring after 12-18 hours, the seleno-organic compound Ebselen, which has a glutathione peroxidase-like activity, and the membrane permeable ascorbic acid derivative CV-3611 have been demonstrated to be effective [11].

Biological context of CCRIS 4543

• We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation [5].
• The effects of CV-3611, a new free radical scavenger, on coronary circulation failure and infarct size after ischemia/reperfusion were studied in conscious beagle dogs [12].

Anatomical context of CCRIS 4543

• SOD, SOD + CAT, L-SOD, CV-3611, and CoQ10 were administered into the left atrium prior to reperfusion [13].
• Histologic and fluorochrome bone-labeling analyses demonstrated improved overall viability of osteocytes, osteoblasts, and marrow cells in the CV-3611-treated group compared to controls [14].
• The CV-3611-treated group had statistically significant improvement in the ratio of lacunae, maintained osteogenetic ability, and preserved normal growth plate architecture after 6 hr of ischemia [14].
• These results indicate that administration of CV-3611 prior to reperfusion can prevent reperfusion damage in bone tissue and maintain osteogenetic ability [14].

Associations of CCRIS 4543 with other chemical compounds

• Coronary blood flow in the control group was reduced to 20% of the preocclusion level at 7 days after reperfusion, whereas in the CV-3611 and alpha-tocopherol treated groups, the decreased coronary flow was remarkably suppressed [12].

Analytical, diagnostic and therapeutic context of CCRIS 4543

• Dogs were randomly assigned to receive CV-3611 (5 mg.kg-1.[5 min]-1, intravenously) just before the onset of reperfusion [15].
• Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01) [5].
• The circulation half life of CV-3611 was checked by a reversed-phase HPLC after 10 mg/kg s.c. administration [16].

References