Disease relevance of C12323

• To assess whether inhibition of the accumulation of LCACs modified the electrophysiological alterations during ischemia, muscles were pretreated with either sodium 2-(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (POCA, 10 mumol/L) or oxfenicine (100 mumol/L), inhibitors of carnitine acyltransferase I [1].
• Both POCA and oxfenicine completely prevented the increase in LCACs even with 40 minutes of ischemia (138 +/- 37 and 56 +/- 4 pmol/mg protein, respectively), associated with a marked delay in the onset and progression of cellular uncoupling and ischemic contracture [1].
• Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris [2].
• Oxfenicine (S-4-OH-phenyl-glycine) was proposed as a compound which would stimulate carbohydrate utilization in the heart and thus reduce oxygen requirement, especially in ischemic heart disease [3].
• Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism [4].

High impact information on C12323

• The oxfenicine group had significantly lower lactate output integrals (1.11+/-0.23 vs. 0.60+/-0.11 mmol) and glycogen depletion (66+/-6 vs. 43+/-8%), and higher anterior wall power index (0.95+/-0.17 vs. 1.30+/-0.11%) and anterior wall energy efficiency index (91+/-17 vs. 129+/-10%) [5].
• Oxfenicine-induced accumulation of lipid in the rat myocardium [6].
• Potential protective value of enhanced myocardial carbohydrate utilisation with reduced free fatty acid uptake after UK 25842 in patients with coronary artery disease [proceedings] [7].
• Steady-state conditions were reached after four minutes of increased flow, when perfusion pressure increased by about 70 and 65 % under control conditions and during hexanoate, respectively, but only by 45 % during oxfenicine [8].
• In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine-palmitoyl-transferase I (CPT-I) with oxfenicine (2 mM) [9].

Chemical compound and disease context of C12323

• RESULTS: During demand-induced ischemia, the oxfenicine group had a higher rate of glucose oxidation (6.9+/-1.1 vs. 4. 7+/-0.8 micromol min(-1); P<0.05), significantly lower fatty acid uptake, but no change in total or active PDH activity [5].
• Both perhexiline (2 microM only) and oxfenicine attenuated (p < 0.003, p < 0.0002, respectively) increases in diastolic tension during ischemia, without significant effects on developed tension, or on cardiac function during reperfusion [10].
• Oxfenicine reduced the recovery of contraction (fasted control 88 +/- 6%, fasted treated 60 +/- 11%, P < 0.05) and increased lactate production of fasted group and attenuated the contracture in the fed [11].
• 14CO2 production from labeled palmitate was decreased by 55% (P less than 0.025) at normal flows in oxfenicine-treated hearts and was reduced further during ischemia [12].
• Effects of fasting, hypoxia, methylpalmoxirate and oxfenicine on the tissue-levels of long-chain acyl CoA and acylcarnitine in the rat atria [13].

Biological context of C12323

• The effect of Oxfenicine on cardiac carbohydrate metabolism in intact dogs [14].
• Perhexiline, but not the active metabolite of oxfenicine, also inhibited cardiac CPT-2 with similar IC50 and Emax, although lower Hill slope, compared with CPT-1 [10].
• In cardiac denervated dogs, with a known inhibition of glycolysis, Oxfenicine increased glucose oxidation from 4.8 to 23.5% [14].
• Inasmuch lactate output did not change and these effects manifested only in the atria predisposed to the utilization of endogenous lipids, it may be inferred that oxfenicine preserved the atrial functions through the inhibition of fatty acid oxidation [15].
• The analyses were also sensitive to the influence of pharmacological intervention with oxfenicine in that several parameters lost statistical significance for percentage systolic shortening and two were added (heart rate and end-diastolic length) for the length-pressure loop [16].

Anatomical context of C12323

• Oxfenicine treatment of food-restricted animals partially preserved the isomyosin profile of the FE-M group (P less than 0.05), suggesting that, within the context of food restriction, cardiac metabolism can influence cardiac isomyosin distribution independently of thyroid status [17].

Associations of C12323 with other chemical compounds

• The effects on myocardial damage of metabolic interventions by nicotinic acid, oxfenicine, or a combination of the two were assessed in open-chest dogs exposed to coronary artery occlusion for 6 hours [18].
• In female hearts perfused with oxfenicine, however, recovery of systolic pressure, cardiac output, and ventricular contraction was significantly increased compared with control hearts (P < 0.05) [19].
• These possibilities were evaluated using oxfenicine, a CPT-I inhibitor, and alternate substrates that bypass carnitine-dependent metabolism [20].
• The noxious effects of oxfenicine, attained after the glucose metabolism was eliminated, lend direct evidence to the notion that endogenous triacylglycerol supports, at least partly, the atrial functions [21].
• Oxfenicine, an FA oxidation inhibitor, did not alter the inhibitory effect of 60 microM oleate on HR-LPL [22].

Analytical, diagnostic and therapeutic context of C12323

• Oxfenicine (33 mg/kg) was administered systemically by bolus injection at time 0 and 60 minutes of perfusion in nine animals [23].
• The series were repeated in another 6 animals, but oxfenicine (CPT I inhibitor) preceeded Intralipid during reperfusion [24].
• Four groups of rats were used in the experiment (12 to 14 rats in each group), and each group received two subcutaneous injections, the second injection 25 min after the first, of oxfenicine-isoproterenol, oxfenicine-saline, saline-isoproterenol and saline twice, respectively [6].

References