ubiquinone and propionylcarnitine

The inability of heart muscle to generate ventricular pressure to adequately propel blood through the cardiovascular system is a primary defect associated with congestive heart failure (CHF). Force-frequency relationship (FFR) is one of the main cardiac defects associated with congestive heart failure. Thus FFR is a convenient methodological tool for evaluating the severity of muscle contractile dysfunction and the effectiveness of therapeutic agents. Papillary muscle isolated from BIO TO-2 cardiomyopathic Syrian hamsters (CMSHs), show a depressed FFR and represents an animal model of human idiopathic dilated cardiomyopathy. In the present study we investigated the effect of CoQ10, omega-3 fatty acids, propionyl-L-carnitine (PLC) and a combination of these 3 agents (formulation HS12607) on FFR in 8 month old BIO TO-2 CMSHs. Papillary muscles isolated from the anesthetized animals were placed in an incubation bath and attached to an isometric force transducer. A digital computer with an analog/digital interface allowed control of both muscle developed force and electrical stimulus parameters. Force-frequency response was evaluated, at Lmax, with increasing frequencies: 0.06, 0.12, 0.25, 0.5, 1, 2 and 4 Hz. HS12607-treatment produced a positive inotropic effect resulting in a significant enhancement (p < 0.05) of the peak force at the highest frequencies (1-4 Hz). In the range of frequency of 1-4 Hz also CoQ10 and omega-3 significantly (p < 0.05) attenuated the fractional decline in developed force. The significant improvement (p < 0.05) of the timing parameter peak rate of tension rise (+ T') and peak rate of tension fall (-T') indicating a faster rate of muscle contraction and relaxation respectively, found in CoQ10, omega-3 and PLC-treated CMSHs, may be due to the positive effects of these substances on sarcoplasmic reticulum functions. These findings suggest that naturally occurring CoQ10, omega-3 and PLC, particularly when administered together in a coformulation, might be a valid adjuvant to conventional therapy in dilated cardiomyopathy especially when considering that they are natural substances, devoid of side effects.

Topics: Animals; Cardiomyopathies; Cardiomyopathy, Dilated; Carnitine; Cricetinae; Fatty Acids, Omega-3; Male; Mesocricetus; Models, Animal; Myocardial Contraction; Papillary Muscles; Stimulation, Chemical; Ubiquinone

A coformulation of essential factors, i.e. propionyl-L-carnitine (PLC), coenzyme Q10 (CoQ10), nicotinamide (NAM), riboflavin and pantothenic acid, was administered orally to Wistar rats for 7 weeks and its efficacy was tested through in vivo and in vitro techniques in improving motor functions of striated, cardiac and smooth musculature of the rat. In vivo experiments showed that long-term supplementation significantly improved horizontal locomotor activity by about 19% in male and 26% in female rats. Maximum values of shortening velocity, work and power were significantly increased (P<.05) in papillary muscle isolated from treated rats. A positive inotropic effect was also observed on colonic smooth muscle strips upon treatment. Work was the most affected parameter and it increased by 160% in smooth muscle from treated animals. The present results indicate that supplementation with the combination of the above mentioned substances elicits positive functional changes on motor performance of skeletal, cardiac and smooth muscle of the rat.

Topics: Animals; Antioxidants; Blood Pressure; Body Weight; Carnitine; Coenzymes; Drug Combinations; Energy Metabolism; Female; Heart; Heart Rate; Male; Motor Activity; Muscle, Skeletal; Muscle, Smooth; Niacinamide; Organ Size; Pantothenic Acid; Papillary Muscles; Rats; Rats, Wistar; Riboflavin; Sex Characteristics; Ubiquinone

Anthracycline derivatives are among the most effective and widely used antiblastic drugs. Irreversible and dose-dependent cardiotoxic side effects, however, severely limit their prolonged use. This study sought to establish whether carnitine derivatives or coenzyme Q10 could provide protection against doxorubicin-related cardiac damage. Rat heart slices were incubated for 60 min in a Warburg apparatus at 38 degrees C with 4 mM L-carnitine or 1 mM propionyl carnitine or 15 microM coenzyme Q10 to which 25 microM doxorubicin was added. Cellular oxygen uptake and 14C-leucine incorporation were measured. Carnitine derivatives significantly reduced (p less than 0.001) the metabolic cardiac impairment due to doxorubicin. Incubation for 60 min with a mixture of L-carnitine and doxorubicin improved cellular respiration, oxygen uptake being only 9% less than that of the controls, and an even greater reversal characterized the propionyl carnitine mixture for which the recovery of endogenous cellular respiration was almost complete (93%). Coenzyme Q10 instead provided no significant protection against doxorubicin-induced inhibition. The incorporation of 14C-leucine followed a similar pattern; the addition of carnitine derivatives to doxorubicin served to restore cellular protein synthesis almost totally (from 76 to 97%), whereas coenzyme Q10 produced no significant increment, probably due to the low permeability of the cell membrane to exogenous coenzyme Q10. Thus, levo and propionyl carnitine even more appear to be promising agents in the prevention of doxorubicin-related cardiac toxicity.

Topics: Animals; Carnitine; Doxorubicin; Heart; Male; Muscle Proteins; Myocardium; Oxygen; Rats; Rats, Inbred Strains; Ubiquinone