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Sample records for carnitine o-palmitoyltransferase

  1. Carnitine

    Science.gov (United States)

    Carnitine (L-g-trimethylamino-ß-hydroxybutyrate) functions metabolically as a covalent molecular chaperone of acyl compounds esterified to its hydroxyl moiety (1,2). The quintessentialmetabolic function of L-carnitine is to shuttle long-chain FAs (LCFAs)2 across the inner mitochondrial membrane to t...

  2. Carnitine acetyltransferase

    DEFF Research Database (Denmark)

    Berg, Sofia Mikkelsen; Beck-Nielsen, Henning; Færgeman, Nils Joakim

    2017-01-01

    Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained...

  3. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn

    2015-01-01

    Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

  4. Carnitine biosynthesis in mammals

    NARCIS (Netherlands)

    Vaz, Frédéric M.; Wanders, Ronald J. A.

    2002-01-01

    Carnitine is indispensable for energy metabolism, since it enables activated fatty acids to enter the mitochondria, where they are broken down via beta-oxidation. Carnitine is probably present in all animal species, and in numerous micro-organisms and plants. In mammals, carnitine homoeostasis is

  5. Primary Carnitine Deficiency

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Hougaard, David M; Sandhu, Noreen

    2017-01-01

    Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth...

  6. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

    NARCIS (Netherlands)

    Boer, L. de; Kluijtmans, L.A.J.; Morava, E.

    2013-01-01

    Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1-5 muM, normal 20-55 muM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of

  7. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

    OpenAIRE

    de Boer, L.; Kluijtmans, L. A. J.; Morava, E.

    2012-01-01

    Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1–5 μM, normal 20–55 μM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of 1 year, after interruption of carnitine supplementation for a 4-week period the carnitine profile was assessed and the free carnitine level had dropped to 10.4 μmol/l (normal: 20–55 μM) and total car...

  8. DISORDERS OF CARNITINE TRANSPORT AND THE CARNITINE CYCLE

    OpenAIRE

    Longo, Nicola; di San Filippo, Cristina Amat; Pasquali, Marzia

    2006-01-01

    Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta ox...

  9. Carnitine derivatives: clinical usefulness.

    Science.gov (United States)

    Malaguarnera, Mariano

    2012-03-01

    Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.

  10. Role of carnitine in disease

    Directory of Open Access Journals (Sweden)

    Flanagan Judith L

    2010-04-01

    Full Text Available Abstract Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.

  11. Carnitine palmityl transferase I deficiency

    NARCIS (Netherlands)

    Al-Aqeel, A. I.; Rashed, M. S.; Ruiter, J. P.; Al-Husseini, H. F.; Al-Amoudi, M. S.; Wanders, R. J.

    2001-01-01

    Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected

  12. Relative Carnitine Deficiency in Autism

    Science.gov (United States)

    Filipek, Pauline A.; Juranek, Jenifer; Nguyen, Minh T.; Cummings, Christa; Gargus, J. Jay

    2004-01-01

    A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine ([rho] less than 0.001), and pyruvate ([rho]=0.006) were significantly reduced…

  13. Partial muscle carnitine palmitoyltransferase-A deficiency

    International Nuclear Information System (INIS)

    Ross, N.S.; Hoppel, C.L.

    1987-01-01

    After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event

  14. Partial muscle carnitine palmitoyltransferase-A deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Ross, N.S.; Hoppel, C.L.

    1987-01-02

    After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event.

  15. PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation

    NARCIS (Netherlands)

    van Vlies, Naomi; Ferdinandusse, Sacha; Turkenburg, Marjolein; Wanders, Ronald J. A.; Vaz, Frédéric M.

    2007-01-01

    In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured

  16. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Engel, A.G.

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and ''other tissues'') was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract

  17. Carnitine transport and fatty acid oxidation.

    Science.gov (United States)

    Longo, Nicola; Frigeni, Marta; Pasquali, Marzia

    2016-10-01

    Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B(0,+). Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients' fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler

  18. The plasma carnitine concentration regulates renal OCTN2 expression and carnitine transport in rats

    OpenAIRE

    Schürch, R; Todesco, L; Novakova, K; Mevissen, M; Stieger, B; Krähenbühl, S

    2010-01-01

    Previous findings in rats and in human vegetarians suggest that the plasma carnitine concentration and/or carnitine ingestion may influence the renal reabsorption of carnitine. We tested this hypothesis in rats with secondary carnitine deficiency following treatment with N-trimethyl-hydrazine-3-propionate (THP) for 2 weeks and rats treated with excess L-carnitine for 2 weeks. Compared to untreated control rats, treatment with THP was associated with an approximately 70% decrease in plasma car...

  19. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

    OpenAIRE

    Rebouche, C J; Engel, A G

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine wa...

  20. Synthesis of carboxy-labelled 1-carnitine

    International Nuclear Information System (INIS)

    Goodfellow, D.B.; Hoppel, C.L.; Turkaly, J.S.

    1982-01-01

    A method for the production of carboxy-labelled l-carnitine is described. The first step is the chemical synthesis of 4-N-trimethylammoniobutanoate (butyrobetaine) from the precursors 4-aminobutanoate and iodomethane. The second step involves the hydroxylation of butyrobetaine to form l-carnitine using butyrobetaine hydroxylase partially purified from bovine calf liver. The method also can be used to synthesize Me-labelled and uniformly-chain-labelled l-carnitine. (author)

  1. The Effect of Carnitine Supplementation on Hyperammonemia and Carnitine Deficiency Treated with Valproic Acid in a Psychiatric Setting

    OpenAIRE

    Nakamura, Masaru; Nagamine, Takahiko

    2015-01-01

    Objective: The aim of this study was to investigate the effect of levocarnitine (active isoform of carnitine, L-Carnitine) supplementation on serum ammonia and carnitine levels simultaneously, and their clinical outcomes in valproic acid-treated psychiatric subjects.

  2. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency

    NARCIS (Netherlands)

    Tang, N. L.; Ganapathy, V.; Wu, X.; Hui, J.; Seth, P.; Yuen, P. M.; Wanders, R. J.; Fok, T. F.; Hjelm, N. M.

    1999-01-01

    Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age,

  3. Uptake of carnitine by red blood cells

    International Nuclear Information System (INIS)

    Campa, M.; Borum, P.

    1986-01-01

    A significant amount of blood carnitine (70% of cord blood and 40% of blood from healthy adults) is partitioned into the red blood cell compartment of whole blood. Data indicate that the plasma compartment and the red blood cell compartment of whole blood represent different metabolic pools of carnitine. There are no data to indicate that red blood cells synthesize carnitine, but our understanding of the uptake of carnitine by red blood cells is negligible. Red blood cells were obtained from healthy adults, washed twice with normal saline, and used for uptake experiments. When the cells were incubated at 37 0 C in the presence of 14 C-carnitine, radioactivity was found both in the soluble cytosolic and membrane fractions of the cells following lysis. The uptake was dependent upon the time of incubation, temperature of incubation, and carnitine concentration in the incubation medium. Washed red blood cell membranes incubated with 14 C-carnitine showed specific binding of radioactivity. These data are consistent with the hypothesis that red blood cells have an uptake mechanism for L-carnitine

  4. Molecular enzymology of carnitine transfer and transport

    NARCIS (Netherlands)

    Ramsay, RR; Gandour, RD; van der Leij, FR

    2001-01-01

    Carnitine (L-3-hydroxy-4-N-trimethylaminobutyric acid) forms esters with a wide range of acyl groups and functions to transport and excrete these groups. It is found in most cells at millimolar levels after uptake via the sodium-dependent carrier, OCTN2. The acylation state of the mobile carnitine

  5. Enzymology of the Carnitine Biosynthesis Pathway

    NARCIS (Netherlands)

    Strijbis, Karin; Vaz, Frédéric M.; Distel, Ben

    2010-01-01

    The water-soluble zwitterion carnitine is an essential metabolite in eukaryotes required for fatty acid oxidation as it functions as a carrier during transfer of activated acyl and acetyl groups across intracellular membranes. Most eukaryotes are able to synthesize carnitine endogenously, besides

  6. Secondary Carnitine Deficiency in Dialysis Patients: Shall We Supplement It?

    OpenAIRE

    Ronald J.A. Wanders; Tim Ulinski; Stephanie E. Reuter; Asha Moudgil

    2016-01-01

    Carnitine, essential for fatty acid β-oxidation, is obtained from diet and through de novo biosynthesis. The organic cation/carnitine transporter 2 (OCTN2) facilitates carnitine cellular transport and kidney resorption. Carnitine depletion occurs in OCTN2-deficient patients, with serious clinical complications including cardiomyopathy, myopathy, and hypoketotic hypoglycaemia. Neonatal screening can detect OCTN2 deficiency. OCTN2-deficiency is also known as primary carnitine deficiency. Carnit...

  7. l-Carnitine and heart disease.

    Science.gov (United States)

    Wang, Zhong-Yu; Liu, Ying-Yi; Liu, Guo-Hui; Lu, Hai-Bin; Mao, Cui-Ying

    2018-02-01

    Cardiovascular disease (CVD) is a key cause of deaths worldwide, comprising 15-17% of healthcare expenditure in developed countries. Current records estimate an annual global average of 30 million cardiac dysfunction cases, with a predicted escalation by two-three folds for the next 20-30years. Although β-blockers and angiotensin-converting-enzymes are commonly prescribed to control CVD risk, hepatotoxicity and hematological changes are frequent adverse events associated with these drugs. Search for alternatives identified endogenous cofactor l-carnitine, which is capable of promoting mitochondrial β-oxidation towards a balanced cardiac energy metabolism. l-Carnitine facilitates transport of long-chain fatty acids into the mitochondrial matrix, triggering cardioprotective effects through reduced oxidative stress, inflammation and necrosis of cardiac myocytes. Additionally, l-carnitine regulates calcium influx, endothelial integrity, intracellular enzyme release and membrane phospholipid content for sustained cellular homeostasis. Carnitine depletion, characterized by reduced expression of "organic cation transporter-2" gene, is a metabolic and autosomal recessive disorder that also frequently associates with CVD. Hence, exogenous carnitine administration through dietary and intravenous routes serves as a suitable protective strategy against ventricular dysfunction, ischemia-reperfusion injury, cardiac arrhythmia and toxic myocardial injury that prominently mark CVD. Additionally, carnitine reduces hypertension, hyperlipidemia, diabetic ketoacidosis, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, etc. that enhance cardiovascular pathology. These favorable effects of l-carnitine have been evident in infants, juvenile, young, adult and aged patients of sudden and chronic heart failure as well. This review describes the mechanism of action, metabolism and pharmacokinetics of l-carnitine. It specifically emphasizes upon the beneficial

  8. Primary Carnitine deficiency in the Faroe Islands

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Køber, Lars; Lund, Allan M

    2014-01-01

    BACKGROUND: Carnitine deficiency can cause cardiomyopathy and cardiac arrhythmia. The prevalence in the Faroe Islands is the highest reported in the world (1:300). A nationwide screening program identified 76 Faroese adult patients (15-80 years) with Primary Carnitine Deficiency (PCD). We describe...... prior and current health status and symptoms in these patients, especially focusing on cardiac characteristics. METHODS: Upon identification, patients were immediately admitted for physical examination, ECG, blood tests and initiation of L-carnitine supplementation. Medical records were reviewed...... and patients were interviewed. Echocardiography and blood tests were performed in 35 patients before and after L-carnitine supplementation. RESULTS: All patients were either asymptomatic or had minor symptoms when diagnosed. Echocardiography including LVEF, global longitudinal strain and dimensions were normal...

  9. Carnitine supplementation and depletion: tissue carnitines and enzymes in fatty acid oxidation.

    Science.gov (United States)

    Negrao, C E; Ji, L L; Schauer, J E; Nagle, F J; Lardy, H A

    1987-07-01

    Sixty-two male rats were randomly assigned into a 3 X 2 X 2 factorial design containing 12 groups according to carnitine treatment, exercise training (treadmill, 1 h, 5 times/wk, 8 wk, 26.8 m/min, 15% grade), and physical activity [rested for 60 h before they were killed or with an acute bout of exercise (1 h, 26.8 m/min, 15% grade) immediately before they were killed]. Isotonic saline was injected intraperitoneally 5 times/wk in the controls, whereas 750 mg/kg of L- or D-carnitine, respectively, were injected in the supplemented and depleted treatment groups. A significant increase in free and short-chain acyl carnitine concentration in skeletal muscle and heart was observed in L-carnitine supplemented rats, whereas a significant reduction in skeletal muscle, heart, and liver occurred in rats depleted of L-carnitine. Long-chain acyl carnitine in all tissues was not altered by carnitine treatment; training increased plasma and liver concentrations, whereas acute exercise decreased skeletal muscle and increased liver concentrations. An acute bout of exercise significantly increased short-chain acylcarnitine in liver, regardless of carnitine and/or training effects. beta-Hydroxyacyl-CoA dehydrogenase activity in skeletal muscle was induced by training but reduced by depletion. Carnitine acetyltransferase (CAT) was significantly increased in heart by L-carnitine supplementation, whereas it was reduced by depletion in skeletal muscle. Exercise training significantly increased CAT activity in skeletal muscle but not in heart, whereas acute exercise significantly increased activity in both tissues. Carnitine palmitoyltransferase activity was increased by acute exercise in the heart in only the supplemented and exercise-trained rats.

  10. Mechanisms for altered carnitine content in hypertrophied rat hearts

    International Nuclear Information System (INIS)

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-01-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-[ 14 C]carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by ∼20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels

  11. Altered carnitine transport in pressure-overload hypertrophied rat hearts

    International Nuclear Information System (INIS)

    O'Rourke, B.; Foster, K.; Reibel, D.K.

    1986-01-01

    The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L- 14 C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 μM carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 μM carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart

  12. Effect of L-carnitine supplementation on drake semen quality

    African Journals Online (AJOL)

    sp3

    2014-01-30

    Jan 30, 2014 ... This study was conducted to determine the effect on semen quality traits of supplementing the diets of. Iraqi drakes with L-carnitine. ... Keywords: Carnitine, ducks, reproductive performance ..... clinical result. Drug Exp. Clin.

  13. Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions CACT deficiency Carnitine-acylcarnitine translocase deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that ...

  14. Effect of [L-Carnitine] on acetyl-L-carnitine production by heart mitochondria

    International Nuclear Information System (INIS)

    Bieber, L.L.; Lilly, K.; Lysiak, W.

    1986-01-01

    The authors recently reported a large efflux of acetyl-L-carnitine from rat heart mitochondria during state 3 respiration with pyruvate as substrate both in the presence and absence of malate. In this series of experiments, the effect of the concentration of L-carnitine on the efflux of acetyl-L-carnitine and on the production of 14 CO 2 from 2- 14 C-pyruvate was determined. Maximum acetylcarnitine production (approximately 25 n moles/min/mg protein) was obtained at 3-5 mM L-carnitine in the absence of added malate. 14 CO 2 production decreased as the concentration of L-carnitine increased; it plateaued at 3-5 mM L-carnitine. These data indicate carnitine can stimulate flux of pyruvate through pyruvate dehydrogenase and can reduce flux of acetyl CoA through the Krebs cycle by acting as an acceptor of the acetyl moieties of acetyl CoA generated by pyruvate dehydrogenase

  15. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    International Nuclear Information System (INIS)

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium

  16. Carnitine for fatigue in multiple sclerosis.

    Science.gov (United States)

    Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

    2012-05-16

    Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active

  17. Does carnitine have a role in fat absorption?

    International Nuclear Information System (INIS)

    Leichter, J.; Ottem, A.; Hahn, P.

    1987-01-01

    The effect of D-carnitine and tetradecylglycidic acid (TDGA), an inhibitor of carnitine palmitoyltransferase, on intestinal absorption of palmitic acid was determined. The proximal intestinal segment was ligated in adult male rats and filled with 0.5 μCi of 14 C-palmitic acid alone or with either D-carnitine or TDGA. Thirty minutes alter the radioactivity was determined in the intestinal lumen, intestinal wall and plasma. The absorption of palmitic acid was decreased in the presence of D-carnitine (10 mg/ml) as evidenced by significantly lower levels of radioactivity in the gut wall and the plasma and by significantly greater residual radioactivity in the lumenal contents. L-carnitine had no effect on plasma radioactivity but if D- and L-carnitine were given together the effect of D-carnitine was still in evidence. TDGA also inhibited intestinal absorption of palmitic acid. 8 references, 2 tables

  18. Effects of oral L-carnitine and DL-carnitine supplementation on alloxan-diabetic rats

    Directory of Open Access Journals (Sweden)

    Roberto Barbosa Bazotte

    2012-02-01

    Full Text Available The effect of oral L-carnitine (LC or DL-carnitine (DLC supplementation during one or four weeks (200 or 400 mg.kg-1.day-1 in diabetic rats was investigated. After the supplementation period, the blood was collected for the evaluation of total (TC and free L-carnitine (FC, glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C and triacylglycerol. Tissues were collected for the determination of TC and FC concentrations. The carnitine supplementation did not change levels of glucose, total cholesterol, HDL-C and LDL-C in the blood. Diabetic rats showed hypertriacylglycerolemia and decreased blood and tissue levels of FC and TC. Normalization of the blood triacylglycerol and increased blood and tissue levels of FC and TC were observed with the LC or DLC supplementation. However, the hyperglycemia remained unchanged. Thus, the reduction of blood triacylglycerol obtained with carnitine supplementation in the diabetic rats did not depend on an amelioration in the glycemia and was mediated partly at least by an increment of serum and tissue concentrations of FC and TC.

  19. Kinetic compartmental analysis of carnitine metabolism in the dog

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Engel, A.G.

    1983-01-01

    This study was undertaken to quantitate the dynamic parameters of carnitine metabolism in the dog. Six mongrel dogs were given intravenous injections of L-[methyl-3H]carnitine and the specific radioactivity of carnitine was followed in plasma and urine for 19-28 days. The data were analyzed by kinetic compartmental analysis. A three-compartment, open-system model [(a) extracellular fluid, (b) cardiac and skeletal muscle, (c) other tissues, particularly liver and kidney] was adopted and kinetic parameters (carnitine flux, pool sizes, kinetic constants) were derived. In four of six dogs the size of the muscle carnitine pool obtained by kinetic compartmental analysis agreed (+/- 5%) with estimates based on measurement of carnitine concentrations in different muscles. In three of six dogs carnitine excretion rates derived from kinetic compartmental analysis agreed (+/- 9%) with experimentally measured values, but in three dogs the rates by kinetic compartmental analysis were significantly higher than the corresponding rates measured directly. Appropriate chromatographic analyses revealed no radioactive metabolites in muscle or urine of any of the dogs. Turnover times for carnitine were (mean +/- SEM): 0.44 +/- 0.05 h for extracellular fluid, 232 +/- 22 h for muscle, and 7.9 +/- 1.1 h for other tissues. The estimated flux of carnitine in muscle was 210 pmol/min/g of tissue. Whole-body turnover time for carnitine was 62.9 +/- 5.6 days (mean +/- SEM). Estimated carnitine biosynthesis ranged from 2.9 to 28 mumol/kg body wt/day. Results of this study indicate that kinetic compartmental analysis may be applicable to study of human carnitine metabolism

  20. Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis.

    Science.gov (United States)

    Blanchard, Géraldine; Paragon, Bernard M; Milliat, Fabien; Lutton, Claude

    2002-02-01

    This study was designed to determine whether dietary carnitine supplement could protect cats from ketosis and improve carnitine and lipid metabolism in experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine during obesity development. Plasma fatty acid, beta-hydroxybutyrate and carnitine, and liver and muscle carnitine concentrations were measured during experimental induction of FHL and after treatment. In control cats (CL group), fasting and FHL increased the plasma concentrations of fatty acids two- to threefold (P 10-fold (from a basal 0.22 +/- 0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In carnitine-supplemented cats, these variables increased significantly (P < 0.0001) only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine supplementation significantly increased plasma, muscle and liver carnitine concentrations. Liver carnitine concentration increased dramatically from the obese state to FHL in nonsupplemented cats, but not in supplemented cats, which suggests de novo synthesis of carnitine from endogenous amino acids in control cats and reversible storage in supplemented cats. These results demonstrate the protective effect of a dietary L-carnitine supplement against fasting ketosis during obesity induction. Increasing the L-carnitine level of diets in cats with low energy requirements, such as after neutering, and a high risk of obesity could therefore be recommended.

  1. Muscle contraction increases carnitine uptake via translocation of OCTN2

    International Nuclear Information System (INIS)

    Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

    2012-01-01

    Highlights: ► Muscle contraction augmented carnitine uptake into rat hindlimb muscles. ► An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. ► Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. ► OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL uptake ) of L-[ 3 H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL uptake of [ 14 C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL uptake of L-[ 3 H]carnitine in the contracting muscles increased 1.4–1.7-fold as compared to that in the contralateral resting muscles (p uptake of [ 14 C]IAP was much higher than that of L-[ 3 H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  2. Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of L-Carnitine Supplementation

    DEFF Research Database (Denmark)

    Rasmussen, J; Thomsen, J A; Olesen, J H

    2015-01-01

    Background: Primary carnitine deficiency (PCD) is a disorder of fatty acid oxidation with a high prevalence in the Faroe Islands. Only patients homozygous for the c.95A>G (p.N32S) mutation have displayed severe symptoms in the Faroese patient cohort. In this study, we investigated carnitine levels...... in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with L-carnitine in patients homozygous for c.95A>G. Methods: Five male patients homozygous for c.95A>G were included. Regular L-carnitine supplementation was stopped and the patients were observed during...... five days. Blood and urine were collected throughout the study. Skeletal muscle biopsies were obtained at 0, 48, and 96 h. Results: Mean skeletal muscle free carnitine before discontinuation of L-carnitine was low, 158 nmol/g (SD 47.4) or 5.4% of normal. Mean free carnitine in plasma (fC0) dropped from...

  3. Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome

    International Nuclear Information System (INIS)

    Gahl, W.A.; Bernardini, I.; Dalakas, M.; Rizzo, W.B.; Harper, G.S.; Hoeg, J.M.; Hurko, O.; Bernar, J.

    1988-01-01

    11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-[ 3 H]carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined

  4. Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians.

    Science.gov (United States)

    Novakova, Katerina; Kummer, Oliver; Bouitbir, Jamal; Stoffel, Sonja D; Hoerler-Koerner, Ulrike; Bodmer, Michael; Roberts, Paul; Urwyler, Albert; Ehrsam, Rolf; Krähenbühl, Stephan

    2016-02-01

    More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation. Sixteen vegetarians and eight omnivores participated in this interventional study with oral supplementation of 2 g L-carnitine for 12 weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma carnitine concentration, but maintained skeletal muscle carnitine stores compared to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents were also not different from omnivores. Maximal oxygen uptake (VO2max) and workload (P max) per bodyweight (bicycle spiroergometry) were not significantly different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for 1 h) revealed no significant differences between vegetarians and omnivores (respiratory exchange ratio, blood lactate and muscle metabolites). Supplementation with L-carnitine significantly increased the total plasma carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle carnitine content in vegetarians (13%). Despite this increase, P max and VO2max as well as muscle phosphocreatine, lactate and glycogen were not significantly affected by carnitine administration. Vegetarians have lower plasma carnitine concentrations, but maintained muscle carnitine stores compared to omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine stores and slightly increases the skeletal muscle carnitine content in vegetarians, but without affecting muscle function and energy metabolism.

  5. Serum total and free carnitine levels in children with asthma.

    Science.gov (United States)

    Asilsoy, Suna; Bekem, Ozlem; Karaman, Ozkan; Uzuner, Nevin; Kavukçu, Salih

    2009-02-01

    Serum carnitine is decreased in recurrent pulmonary infections. We aimed to evaluate serum carnitine levels in asthmatic children. Study group consisted of children with stable asthma and those with acute asthma attacks, while control group included healthy children. Attack severity was determined by the pulmonary score system. Total and free carnitine levels were studied in one blood sample from the control group and stable asthmatics and in two samples from children with acute asthma exacerbation during and after the attack. All the 40 patients in the study group had moderate asthma including 30 with acute attack (13 mild and 17 moderate) and 10 with stable asthma. Carnitine levels were significantly lower in acute attack asthmatics than in the stable asthmatics and controls, while there was no significant difference between the latter two groups. Carnitine levels were not different between asthmatics with mild and moderate attack, and were similar during and after an acute attack. Serum carnitine levels decrease in children with moderate asthma during exacerbation of asthma and shortly thereafter. Further studies are needed to evaluate the effect of carnitine treatment on serum carnitine level.

  6. Effect of propionyl-L-carnitine on human endothelial cells

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Scheffer, M.A.

    1991-01-01

    A possible protective effect of propionyl-L-carnitine on human endothelial cells was studied both under basal culture conditions and in the presence of agents capable of influencing oxidative damage, such as glucose/glucose oxidase and oxidized low-density lipoproteins. Propionyl-L-carnitine had no

  7. Functional analysis of mutant human carnitine acylcarnitine translocases in yeast

    NARCIS (Netherlands)

    IJlst, L.; van Roermund, C. W.; Iacobazzi, V.; Oostheim, W.; Ruiter, J. P.; Williams, J. C.; Palmieri, F.; Wanders, R. J.

    2001-01-01

    Long chain fatty acids are translocated as carnitine esters across the mitochondrial inner membrane by carnitine acylcarnitine translocase (CACT). We report functional studies on the mutant CACT proteins from a severe and a mild patient with CACT deficiency. CACT activities in fibroblasts of both

  8. Regulation of carnitine status in ruminants and efficacy of carnitine supplementation on performance and health aspects of ruminant livestock: a review.

    Science.gov (United States)

    Ringseis, Robert; Keller, Janine; Eder, Klaus

    2018-02-01

    Carnitine has long been known to play a critical role for energy metabolism. Due to this, a large number of studies have been carried out to investigate the potential of supplemental carnitine in improving performance of livestock animals including ruminants, with however largely inconsistent results. An important issue that has to be considered when using carnitine as a feed additive is that the efficacy of supplemental carnitine is probably dependent on the animal's carnitine status, which is affected by endogenous carnitine synthesis, carnitine uptake from the gastrointestinal tract and carnitine excretion. The present review aims to summarise the current knowledge of the regulation of carnitine status and carnitine homeostasis in ruminants, and comprehensively evaluate the efficacy of carnitine supplementation on performance and/or health in ruminant livestock by comparing the outcomes of studies with carnitine supplementation in dairy cattle, growing and finishing cattle and sheep. While most of the studies show that supplemental carnitine, even in ruminally unprotected form, is bioavailable in ruminants, its effect on either milk or growth performance is largely disappointing. However, supplemental carnitine appears to be a useful strategy to offer protection against ammonia toxicity caused by consumption of high levels of non-protein N or forages with high levels of soluble N both, in cattle and sheep.

  9. Preparation of crystalline sodium norcarnitine: an easily handled precursor for the preparation of carnitine analogs and radiolabeled carnitine.

    Science.gov (United States)

    Colucci, W J; Turnbull, S P; Gandour, R D

    1987-05-01

    A procedure by which crystalline sodium norcarnitine can be prepared in large quantities and high yields has been developed. Carnitine is selectively demethylated by thiophenoxide ion in N,N-dimethylethanolamine. The reactive thiophenoxide ion is generated in situ by addition of thiophenol to this basic reaction solvent. Hence, sodium thiophenoxide, which has been used in similar applications, but is difficult to prepare, can be avoided. Accordingly, reaction of (R,S)-carnitine followed by aqueous azeotropic distillation of byproducts as well as excess starting materials and then by neutralization with sodium hydroxide gave sodium norcarnitine in 89% yield. (R)-Carnitine gave 91% yield of (R)-norcarnitine zwitterion before neutralization. A method for the facile preparation of radiolabeled (R)-carnitine is also described. Thus, methylation of sodium norcarnitine with methyl iodide in methanolic acetone produced carnitine, which precipitated, and sodium iodide, which was soluble.

  10. Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome due to Cystinosis

    OpenAIRE

    Besouw, M.; Cornelissen, E.; Cassiman, D.; Kluijtmans, L.; van den Heuvel, L.; Levtchenko, E.

    2014-01-01

    Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequ...

  11. Stereoselective synthesis of L-[4-13C]carnitine

    International Nuclear Information System (INIS)

    Unkefer, C.J.; Ehler, D.S.

    1991-01-01

    The stereoselective synthesis of L-[4- 13 C]carnitine was achieved in 5 steps. The label was introduced from K 13 CN into an easily separated diastereomeric pair of 3-deoxy-D-[1- 13 C]aldohexoses. Reductive amination of the labeled aldohexose yielded the corresponding D-1-(dimethylamino)[1- 13 C]alditol which was oxidized in two steps and alkylated with iodomethane to yield L-[4- 13 C]carnitine. The stereochemical integrity at C-2 of the 3-deoxy-D-[1- 13 C]glucose precursor was maintained throughout the synthesis of L-[4- 13 C]carnitine. (author)

  12. Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Nielsen, Olav W; Janzen, Nils

    2014-01-01

    BACKGROUND: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation and has been associated to episodes of sudden death in the Faroe Islands. Data are presented from the nationwide population based Faroese screening program to find people with low carnitine...... levels indicating PCD. METHODS: Whole blood samples from dried blood spots were analysed by tandem mass spectrometry with and without butylation. Genetic analyses were performed in all people with non-butylated free carnitine (fC0) below 7 μmol/L. RESULTS: 55 % (n = 26,462) of the entire population...

  13. Effects of L-Carnitine and Taurine on associated biochemical ...

    African Journals Online (AJOL)

    carnitine and taurine in healthy and alloxan induced diabetes mellitus in rats. Results showed that diabetic rats had significant increase in the levels of plasma glucose, malondialdehyde (MDA), urea, creatinine and the activity of serum asparate ...

  14. Synthesis of carbon-11 labelled (R)-carnitine

    International Nuclear Information System (INIS)

    Holschbach, M.; Hamkens, W.; Roden, W.; Feinendegen, L.E.

    1991-01-01

    A route to 11 C-labelled (R)-carnitine, based on the methylation of the dimethyl derivative is described. Furthermore, a five-step synthesis for the enantiomerically pure precursor is outlined. (author)

  15. Muscle contraction increases carnitine uptake via translocation of OCTN2

    Energy Technology Data Exchange (ETDEWEB)

    Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly

  16. Synthesis of radioactively methyl-labelled (1)-carnitine

    International Nuclear Information System (INIS)

    Ingalls, S.T.; Hoppel, C.L.; Turkaly, J.S.

    1982-01-01

    Commercial (l)-carnitine chloride was N-demethylated by the action of sodium benzenemercaptide in warm N,N-dimethylformamide. The product 4-(N,N-dimethylammonio)-3-hydroxybutanoic acid chloride salt was isolated in good yield by ion exchange chromatography. Methylation of the product by 14 C -iodomethane in dry methanol produced biologically active 4-N-Me- 14 C -(l)-carnitine chloride of high specific activity in excellent yield. (author)

  17. Serum carnitine levels in bone marrow transplant recipients.

    Science.gov (United States)

    Kirvelä, O; Antila, H; Heinonen, O; Toivanen, A

    1990-12-01

    This study investigated plasma carnitine levels in patients undergoing allogenic bone marrow transplantation. The patients received fat-based TPN (50% fat, 50% CHO; calorie: nitrogen ratio 125:1) for an average of 33 +/- 7.5 days. TPN was started before transplantation and stopped when patients were able to eat. Caloric needs were estimated using the Harris-Benedict equation; 150% of the estimated BEE was given for the first two weeks after transplantation. The amount of TPN was gradually decreased as patients resumed their oral intake. All patients had low-normal serum carnitine levels before transplantation. There was no significant change in total or free serum carnitine levels during the course of TPN. However, in patients who had symptoms of graft vs. host reaction (GVH), the highest carnitine values during GVH (total 72.3 +/- 6.5 and free 61.2 +/- 12.4 mumol/l) were significantly higher (p < 0.001) than the baseline values (total 27.1 +/- 9.3 and free 24.9 +/- 9.6 mumol/l) or the highest non GVH values after transplantation (total 32.0 +/- 10.7 and free 29.0 +/- 10.7 mumol/l, respectively). The serum triglyceride, total cholesterol, and HDL cholesterol remained within normal range. In conclusion, bone marrow transplant patients receiving fat-based TPN have normal circulating levels of carnitine. GVH reaction caused an increase in the carnitine levels, which was probably due to increased tissue catabolism.

  18. l-Carnitine Supplementation in Recovery after Exercise

    Directory of Open Access Journals (Sweden)

    Roger Fielding

    2018-03-01

    Full Text Available Given its pivotal role in fatty acid oxidation and energy metabolism, l-carnitine has been investigated as ergogenic aid for enhancing exercise capacity in the healthy athletic population. Early research indicates its beneficial effects on acute physical performance, such as increased maximum oxygen consumption and higher power output. Later studies point to the positive impact of dietary supplementation with l-carnitine on the recovery process after exercise. It is demonstrated that l-carnitine alleviates muscle injury and reduces markers of cellular damage and free radical formation accompanied by attenuation of muscle soreness. The supplementation-based increase in serum and muscle l-carnitine contents is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function thereby reducing hypoxia-induced cellular and biochemical disruptions. Studies in older adults further showed that l-carnitine intake can lead to increased muscle mass accompanied by a decrease in body weight and reduced physical and mental fatigue. Based on current animal studies, a role of l-carnitine in the prevention of age-associated muscle protein degradation and regulation of mitochondrial homeostasis is suggested.

  19. l-Carnitine Supplementation in Recovery after Exercise.

    Science.gov (United States)

    Fielding, Roger; Riede, Linda; Lugo, James P; Bellamine, Aouatef

    2018-03-13

    Given its pivotal role in fatty acid oxidation and energy metabolism, l-carnitine has been investigated as ergogenic aid for enhancing exercise capacity in the healthy athletic population. Early research indicates its beneficial effects on acute physical performance, such as increased maximum oxygen consumption and higher power output. Later studies point to the positive impact of dietary supplementation with l-carnitine on the recovery process after exercise. It is demonstrated that l-carnitine alleviates muscle injury and reduces markers of cellular damage and free radical formation accompanied by attenuation of muscle soreness. The supplementation-based increase in serum and muscle l-carnitine contents is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function thereby reducing hypoxia-induced cellular and biochemical disruptions. Studies in older adults further showed that l-carnitine intake can lead to increased muscle mass accompanied by a decrease in body weight and reduced physical and mental fatigue. Based on current animal studies, a role of l-carnitine in the prevention of age-associated muscle protein degradation and regulation of mitochondrial homeostasis is suggested.

  20. Plasma carnitine concentrations after chronic alcohol intoxication 

    Directory of Open Access Journals (Sweden)

    Alina Kępka

    2013-05-01

    Full Text Available Background: Carnitine transports fatty acids from the cytoplasm to the mitochondrial matrix, where the fatty acids are oxidized. Chronic alcohol consumption reduces the concentration of carnitine and interferes with oxidative processes occurring in the cell.Aim: The assessment of carnitine concentrations in plasma of chronically intoxicated alcohol dependent persons in a 49-day abstinence period.Material/Methods: The study included 31 patients (5 women and 27 men aged from 26 to 60 years (44.6± 8.9 and 32 healthy subjects (15 women and 17 men aged 22-60 years (39.8± 9.4. The patients’ alcohol dependence ranged from 2 to 30 years (13.6± 7.5. Examined subjects consumed 75-700 g of ethanol/day (226.9± 151.5. Plasma concentrations of free and total carnitine were measured three times: at the first (T0, 30th (T30 and 49th (T49 day of hospital detoxification. Free (FC and total (TC carnitine were determined by the spectrophotometric method. Plasma acylcarnitine (AC concentration was calculated from the difference between TC and FC; then the AC/FC ratio was calculated. To determine statistically significant differences for related variables, Student’s t-test was used.Results: At T0, alcoholics had significantly lower concentration of FC and TC (p < 0.05 in plasma, as compared to the control group. In comparison to controls, at T30, plasma TC and FC (p < 0.01 as well as AC (p < 0.001 were reduced. The lowest concentration of TC, FC and AC (p < 0.001was found at T49. The ratio of AC/FC at T0 had a tendency to be higher in alcoholics than in the control group (p = 0.05, whereas at T49 it was significantly lower in alcoholics as compared to the control subjects (p < 0.05.Conclusions: Chronic alcohol intoxication causes a plasma deficiency of carnitine. Forty-nine days of abstinence showed a significant decrease in the concentration of TC, FC and AC. Further research is necessary to clarify whether a low level of plasma carnitine

  1. OCTN3 is a mammalian peroxisomal membrane carnitine transporter

    International Nuclear Information System (INIS)

    Lamhonwah, Anne-Marie; Ackerley, Cameron A.; Tilups, Aina; Edwards, Vernon D.; Wanders, Ronald J.; Tein, Ingrid

    2005-01-01

    Carnitine is a zwitterion essential for the β-oxidation of fatty acids. The role of the carnitine system is to maintain homeostasis in the acyl-CoA pools of the cell, keeping the acyl-CoA/CoA pool constant even under conditions of very high acyl-CoA turnover, thereby providing cells with a critical source of free CoA. Carnitine derivatives can be moved across intracellular barriers providing a shuttle mechanism between mitochondria, peroxisomes, and microsomes. We now demonstrate expression and colocalization of mOctn3, the intermediate-affinity carnitine transporter (K m 20 μM), and catalase in murine liver peroxisomes by TEM using immunogold labelled anti-mOctn3 and anti-catalase antibodies. We further demonstrate expression of hOCTN3 in control human cultured skin fibroblasts both by Western blotting and immunostaining analysis using our specific anti-mOctn3 antibody. In contrast with two peroxisomal biogenesis disorders, we show reduced expression of hOCTN3 in human PEX 1 deficient Zellweger fibroblasts in which the uptake of peroxisomal matrix enzymes is impaired but the biosynthesis of peroxisomal membrane proteins is normal, versus a complete absence of hOCTN3 in human PEX 19 deficient Zellweger fibroblasts in which both the uptake of peroxisomal matrix enzymes as well as peroxisomal membranes are deficient. This supports the localization of hOCTN3 to the peroxisomal membrane. Given the impermeability of the peroxisomal membrane and the key role of carnitine in the transport of different chain-shortened products out of peroxisomes, there appears to be a critical need for the intermediate-affinity carnitine/organic cation transporter, OCTN3, on peroxisomal membranes now shown to be expressed in both human and murine peroxisomes. This Octn3 localization is in keeping with the essential role of carnitine in peroxisomal lipid metabolism

  2. Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency

    NARCIS (Netherlands)

    Vaz, F. M.; Scholte, H. R.; Ruiter, J.; Hussaarts-Odijk, L. M.; Pereira, R. R.; Schweitzer, S.; de Klerk, J. B.; Waterham, H. R.; Wanders, R. J.

    1999-01-01

    Systemic carnitine deficiency is a potentially lethal, autosomal recessive disorder characterized by cardiomyopathy, myopathy, recurrent episodes of hypoketotic hypoglycemia, hyperammonemia, and failure to thrive. This form of carnitine deficiency is caused by a defect in the active cellular uptake

  3. Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency

    NARCIS (Netherlands)

    Rahbeeni, Z.; Vaz, F. M.; Al-Hussein, K.; Bucknall, M. P.; Ruiter, J.; Wanders, R. J.; Rashed, M. S.

    2002-01-01

    Systemic carnitine deficiency (CDSP) (McKusick 212140) is a rare autosomal recessive disease caused by defective plasma membrane uptake of carnitine. The disease is characterized by Reye syndrome, progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonaemia. CDSP is a treatable

  4. Crystal Structure of an L-Carnitine Complex with Pyrogallol[4]arene

    International Nuclear Information System (INIS)

    Fujisawa, I; Takeuchi, D; Kitamura, Y; Okamoto, R; Aoki, K

    2012-01-01

    L-Carnitine is essential for the transport of long-chain fatty acids from cytosol into mitochondria for generating metabolic energy. The survey of crystal structures of carnitine-containing proteins in the Protein Data Bank reveals that carnitine can take several conformations with the quarternary trimethylammonium terminal being always bound to aromatic residues through cation-π interactions in acyltransferases or carnitine-binding proteins. In order to demonstrate the importance of cation-π interaction as a carnitine recognition mechanism in the artificial receptor-ligand system that mimics the carnitine-binding sites, we have determined the crystal structure of a complex formed between L-carnitine and pyrogallol[4]arene (pyrogallol cyclic tetramer: PCT) as a carnitine receptor, 2PCT·2(L-carnitine)·4EtOH. There form two crystallographically independent monomeric [PCT·L-carnitine] substructures, which further form an obliquely arranged capsule-like dimeric [PCT·L-carnitine] 2 structure through a pair of O-H (PCT)···O (L-carnitine) hydrogen bonds. This is the first report of PCT complex with chiral molecules. In each of the two monomeric [PCT·L-carnitine] substructures, the L-carnitine molecule takes the elongated form with an intramolecular hydrogen bond between the hydroxyl group and the carboxylate oxygen, and the cationic trimethylammonium moiety is incorporated into the cavity of the bowl-shaped PCT molecule through cation-π interactions. These features are similar to those at the D-carnitine-binding site in the crystal structure of the glycine betaine/carnitine/choline-binding protein complex.

  5. Production of L-carnitine by secondary metabolism of bacteria

    Directory of Open Access Journals (Sweden)

    Iborra José L

    2007-10-01

    Full Text Available Abstract The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such as Escherichia coli and Proteus sp., which can be used to produce L-carnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially in Escherichia coli as a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production using E. coli and Proteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back between wet and in silico work to optimize this biotransformation.

  6. Screening of carnitine and biotin deficiencies on tandem mass spectrometry.

    Science.gov (United States)

    Hagiwara, Shin-Ichiro; Kubota, Mitsuru; Nambu, Ryusuke; Kagimoto, Seiichi

    2017-04-01

    It is important to assess pediatric patients for nutritional deficiency when they are receiving specific interventions, such as enteral feeding. We focused on measurement of C0 and 3-hydroxyisovalerylcarnitine (C5-OH) with tandem mass spectrometry (MS/MS), which is performed as part of the newborn mass screening. The purpose of this study was to investigate the usefulness of MS/MS for screening carnitine and biotin deficiencies. Forty-two children (24 boys, 18 girls) were enrolled between December 2013 and December 2015. Blood tests, including measurement of serum free carnitine via the enzyme cycling method, and acylcarnitine analysis on MS/MS of dried blood spot (DBS), were performed for the evaluation of nutrition status. Median patient age was 2 years (range, 2 months-14 years). Mean serum free carnitine was 41.8 ± 19.2 μmol/L. In six of the 42 patients, serum free carnitine was 1.00 nmol/L. Therapy-resistant eczema was improved by treatment with additional biotin and a non-hydrolyzed formula. C0 and C5-OH, measured on MS/MS of DBS, were useful for screening carnitine and biotin deficiencies. © 2016 Japan Pediatric Society.

  7. Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Nielsen, Olav W; Lund, Allan M

    2013-01-01

    Several episodes of sudden death among young Faroese individuals have been associated with primary carnitine deficiency (PCD). Patients suffering from PCD have low carnitine levels and can present with metabolic and/or cardiac complications. Pivalic acid exposure decreases carnitine levels...

  8. epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Lehman, L.J.; Olson, L.

    1986-01-01

    Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of epsilon-N-trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of [methyl- 3 H]epsilon-N-trimethyllysine, and approximately 30% of that was incorporated into tissues as [ 3 H]carnitine. Rats given oral supplements of epsilon-N-trimethyllysine (0.5-20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receiving no dietary epsilon-N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary epsilon-N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral epsilon-N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of epsilon-N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of epsilon-N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat

  9. Metabolic fate of dietary carnitine in human adults: Identification and quantification of urinary and fecal metabolites

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Chenard, C.A.

    1991-01-01

    Results of kinetic and pharmacokinetic studies have suggested that dietary carnitine is not totally absorbed and is in part degraded in the gastrointestinal tract of humans. To determine the metabolic fate of dietary carnitine in humans, we administered orally a tracer dose of methyl- 3 H L-carnitine with a meal to subjects who had been adapted to a low-carnitine diet or a high-carnitine diet. Urinary and fecal excretion of radiolabeled carnitine and metabolites was monitored for 5 to 11 d following administration of the test dose. Total radioactive metabolites excreted ranged from 13 to 34% (low carnitine diet) and 27 to 46% (high carnitine diet) of the ingested tracer. Major metabolites found were [ 3 H]trimethylamine N-oxide (8 to 39% of the administered dose; excreted primarily in urine) and [ 3 H]gamma-butyrobetaine (0.09 to 8% of the administered dose; excreted primarily in feces). Urinary excretion of total carnitine was 42 to 95% (high carnitine diet) and 190 to 364% (low carnitine diet) of intake. These results indicate that oral carnitine is 54 to 87% bioavailable from normal Western diets; the percentage of intake absorbed is related to the quantity ingested

  10. Is L-Carnitine Supplementation Beneficial in 3-Methylcrotonyl-CoA Carboxylase Deficiency?

    DEFF Research Database (Denmark)

    Thomsen, Jákup Andreas; Lund, Allan Meldgaard; Olesen, Jess Have

    2015-01-01

    suffered from self-reported fatigue with some alleviation after L-carnitine supplementation. Conclusion: 3-MCCd is common in the Faroe Islands. Some symptomatic 3-MCCd patients may benefit biochemically and clinically from L-carnitine supplementation, a more general recommendation cannot be given....... and muscle tissue with and without L-carnitine supplementation to evaluate the current treatment strategy of not recommending L-carnitine supplementation to Faroese 3-MCCd patients. Methods: Blood and urine samples and muscle biopsies were collected from patients at inclusion and at 3 months. Eight patients...... received L-carnitine supplementation when recruited; five did not. Included patients who received supplementation were asked to stop L-carnitine, the others were asked to initiate L-carnitine supplementation during the study. Symptoms were determined by review of hospital medical records and questionnaires...

  11. The effect of L-carnitine on lipid metabolism in patients on chronic haemodialysis

    DEFF Research Database (Denmark)

    Yderstræde, Knud Bonnet; Pedersen, Fritz Bangsgaard; Dragsholt, C.

    1987-01-01

    Twenty-one patients (median 49 years; range 20-72 years) on chronic haemodialysis (median: 54 months; range 16-154 months) were examined in a clinical controlled trial for the effect of carnitine on hyperlipoproteinaemia. Initial values of serum carnitine were within the normal range. Carnitine...... was added to the dialysis fluid to a final concentration of 100 mumol/l. The trial was carried out for 6 months, and the serum of fasting patients was analysed at monthly intervals for carnitine, triglycerides, HDL-cholesterol, LDL-cholesterol and apolipoprotein A and B. The loss of carnitine...... to the dialysis fluid also was examined, as was the retained amount in those receiving carnitine. We could not confirm the findings of others that carnitine produces lowering of serum triglycerides and increases of serum HDL-cholesterol. The study was extended for another year with ten patients; however...

  12. Free fatty acids profiling in response to carnitine synergize with ...

    African Journals Online (AJOL)

    Background: The objective of this study was to investigate the fatty acids profiling in diabetic rats induced by sterptozocine (STZ) and their response to administration of lutein and carnitine. Materials and methods: Ninety male albino rats were divided into 6 groups as follows: Normal control. The remaining rats were injected ...

  13. Protective role of carnitine synergized with vitamin E against ...

    African Journals Online (AJOL)

    Group III: Rats were injected with vitamin E (100 IU/kg bw, i.p) daily. Group IV: Rats were given carnitine (20 mg/kg bw, i.p) daily .Group V: Rats were injected with ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT ...

  14. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

    Energy Technology Data Exchange (ETDEWEB)

    Hsiao,Y.; Jogl, G.; Esser, V.; Tong, L.

    2006-01-01

    Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.

  15. Therapeutic effects of Laser and L-carnitine against amiodarone ...

    African Journals Online (AJOL)

    Pulmonary toxicity is considered a life- threatening complication of ... Research Center, Faculty of Medicine, Ain .... Laser therapy restores the balance between oxidants and ... No conflict of interest associated with this work. Contribution of .... Fitness. 2014; 149-159. 21. Lee BJ, Lin JS, Lin YC, Lin PT. Effects of L-carnitine.

  16. Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2

    NARCIS (Netherlands)

    Spiekerkoetter, U.; Huener, G.; Baykal, T.; Demirkol, M.; Duran, M.; Wanders, R.; Nezu, J.; Mayatepek, E.

    2003-01-01

    A family of Turkish origin with primary systemic carnitine deficiency in the father and his two sons is described. In all three individuals, the same homozygous mutation in the OCTN2 gene (R471H) was present and carnitine uptake in fibroblasts was deficient. Whereas one boy became symptomatic with a

  17. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

    NARCIS (Netherlands)

    S. Iliceto (Sabino); D. Scrutinio (Domenico); P. Bruzzi (P.); G. D'Ambrosio (Gaetano); A. Boni (Alejandro); M. Di Biase (Matteo); G. Biasco (Giuseppina); P.G. Hugenholtz (Paul); P. Rizzon (Paolo)

    1995-01-01

    textabstractObjectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy

  18. Serum carnitine concentration is decreased in patients with Lyme borreliosis

    Directory of Open Access Journals (Sweden)

    Alina Kępka

    2016-03-01

    Full Text Available Background: Lyme borreliosis (LB is a serious infectious disease. Carnitine plays a crucial role in metabolism and inflammatory responses. Carnitine may be important in improving neuronal dysfunction and loss of neurons. Aim: To evaluate serum carnitine concentration in adult patients with various clinical types of LB. Material/Methods: Groups: 1 patients with erythema migrans (EM, n=16, 2 neuroborreliosis (NB, n=10, 3 post-Lyme disease (PLD, n=22 and healthy controls (HC, n=32. Total (TC and free (FC carnitine were determined with the spectrophotometric method. Results: TC levels (44.9±10.4, 28.0±8.4, 35.9±15.6 μmol/L in the EM, NB and PLD patients were lower than in HC (54.0±11.4 μmol/L, p < 0.001. FC levels (32.7±7.7, 23.6±6.8, 26.3±11.2 μmol/L in the EM, NB and PLD patients were lower than in HC (40.5±7.6 μmol/L, p < 0.001. AC levels (12.2±5.2, 4.4±2.6, 9.6±7.4 μmol/L in the EM, NB and PLD patients were lower in the NB and PLD patients than in HC (13.5±8.40 μmol/L, p <0.001. AC/FC ratio was 0.31±0.14, 0.18±0.09, 0.39±0.33 in the EM, NB and PLD patients. Conclusions: LB patients exhibit a significant decrease of their serum carnitine concentrations. The largest changes were in the NB and PLD patients. To prevent late complications of the disease a possibility of early supplementation with carnitine should be considered. Further studies are required to explain the pathophysiological significance of our findings.

  19. Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine: Pt. 1

    International Nuclear Information System (INIS)

    Reed, K.W.; Ueda, C.T.; Murray, W.J.; Augustine, S.C.

    1989-01-01

    The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of Hl across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identity of 9- or 10-monoiodostearic acid and 9-or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[ 125 I]stearic acid and 9- or 10-monoiodo[ 125 I]stearyl carnitine were synthesized via the isotopic exchange of 125 I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine. (author)

  20. Effects of Carnitine on Sperm Parameters of Infertile Males with Idiopathic Asthenospermia

    Directory of Open Access Journals (Sweden)

    I Amiri

    2008-01-01

    Full Text Available ABSTRACT: Introduction & Objective: Studies confirm that a number of nutritional and environmental factors may negatively affect spermatogenesis and cause male infertility. Carnitine is an important factor for sperm motility. Carnitine deficiency decreases sperm motility and may cause male infertility. The aim of this study was to assess the effects of carnitine on sperm parameters in infertile males with idiopathic asthenospermia. Materials & Methods: This study is a before and after clinical trial performed on 40 asthenospermia men who were treated with 750 mg per/day carnitine in Fatemieh infertility research center in years 2006-2007. Sperm parameters were assessed before and after treatment. The obtained data were analyzed using SPSS10 and paired T-test Results: The results showed a significant increase in sperm concentration, morphology, sperm total motility and rapid progressive motility after treatment by carnitine (p<0.05. Conclusion: Carnitine supplementation has a significant effect on sperm parameters in men with idiopathic asthenospermia.

  1. L-carnitine plasma levels in dogs and cats. A diagnostic parameter?

    International Nuclear Information System (INIS)

    Fischer, J.

    1993-04-01

    The relation between levels of carnitine in plasma and lesions of organs should be demonstrated. 52 dogs and 58 cats examined in veterinary clinics for several reasons and routinely screened for blood chemistry also were analysed for free plasma carnitine by a radiocarbon method. Increased carnitine levels were observed in both species in case of heart, liver and kidney disorders. Additionally the influence of food intake on carnitine levels in dogs was studied. Postprandial changes were insignificant. Because of lack of information about carnitine levels in cats and changes with age plasma carnitine was determined in cats and kittens. The range of normal values was 8.2 to 24.2 μmol/l without any significance of age

  2. The effect of carnitine on some biochemical variables in athletes using nuclear technique

    International Nuclear Information System (INIS)

    Heshmat, H.A.; AbodelAziz, S.M.; El-Arab, A.E.

    2003-01-01

    Carnitine (3-hydroxy-4-N-trimethylaminobutiric acid) ingestion has a positive effect on work performance and duration as well as delaying muscle fatigue in athletes. Carnitine leas to decrease triglycerides concentration by increasing its rate of oxidation, which decrease atherogenic risk in athletes. On the other hand after exercise, there was an increase in triglyceride level in blood due to increased fat utilization. Also, there was an elevation in lactate concentration after exercise and carnitine ingestion, which is, attributes to aerobic glycolysis. Carnitine. Carnitine ingestion lead also to a slight slight decrease in insulin secretion due to the increasing in glucose uptake by skeletal muscle associated with increasing glucose transport (Glut), however, protein density on the sarcolenma independent of insulin. The data obtained revealed that, was an elevation in cortisol level after exercise and it increased dramatically after carnitine ingestion

  3. Gbu Glycine Betaine Porter and Carnitine Uptake in Osmotically Stressed Listeria monocytogenes Cells

    Science.gov (United States)

    Mendum, Mary Lou; Smith, Linda Tombras

    2002-01-01

    The food-borne pathogen Listeria monocytogenes grows actively under high-salt conditions by accumulating compatible solutes such as glycine betaine and carnitine from the medium. We report here that the dominant transport system for glycine betaine uptake, the Gbu porter, may act as a secondary uptake system for carnitine, with a Km of 4 mM for carnitine uptake and measurable uptake at carnitine concentrations as low as 10 μM. This porter has a Km for glycine betaine uptake of about 6 μM. The dedicated carnitine porter, OpuC, has a Km for carnitine uptake of 1 to 3 μM and a Vmax of approximately 15 nmol/min/mg of protein. Mutants lacking either opuC or gbu were used to study the effects of four carnitine analogs on growth and uptake of osmolytes. In strain DP-L1044, which had OpuC and the two glycine betaine porters Gbu and BetL, triethylglycine was most effective in inhibiting growth in the presence of glycine betaine, but trigonelline was best at inhibiting growth in the presence of carnitine. Carnitine uptake through OpuC was inhibited by γ-butyrobetaine. Dimethylglycine inhibited both glycine betaine and carnitine uptake through the Gbu porter. Carnitine uptake through the Gbu porter was inhibited by triethylglycine. Glycine betaine uptake through the BetL porter was strongly inhibited by trigonelline and triethylglycine. These results suggest that it is possible to reduce the growth of L. monocytogenes under osmotically stressful conditions by inhibiting glycine betaine and carnitine uptake but that to do so, multiple uptake systems must be affected. PMID:12406761

  4. Evaluation of serum l-carnitine level in children with acute bronchial asthma

    Directory of Open Access Journals (Sweden)

    Eman Ramadan

    2014-07-01

    Conclusion: According to our study, it could be concluded that l-carnitine decrease is linked to the occurrence of attack of bronchial asthma. Accordingly, it is recommended to make further studies to find out if there is a beneficial role of carnitine intake in the prophylaxis & treatment of attacks of bronchial asthma. The recommended studies should search for the most suitable dose & side effects of carnitine as a potential pharmaceutical agent.

  5. Acetyl-L-carnitine improves aged brain function.

    Science.gov (United States)

    Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

    2010-07-01

    The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

  6. Composition, disintegrative properties, and labeling compliance of commercially available taurine and carnitine dietary products.

    Science.gov (United States)

    Bragg, Rebecca R; Freeman, Lisa M; Fascetti, Andrea J; Yu, Zengshou

    2009-01-15

    To test the quality, disintegration properties, and compliance with labeling regulations for representative commercially available taurine and carnitine dietary products. Evaluation study. 11 commercially available taurine and 10 commercially available carnitine products. For each product, the amount of taurine or carnitine was determined and compared with the label claim. All products were evaluated for concentrations of mercury, arsenic, and selenium. Disintegration properties of 5 taurine and 8 carnitine products were determined in vitro. Labels were evaluated for compliance with FDA guidelines. 10 of 11 taurine and 10 of 10 carnitine products were within 10% of the stated label claim. Three of 11 taurine and 6 of 10 carnitine products were within 5% of the stated label claim. The median percentage difference between laboratory analysis and label claim was -5.7% (range, -26.3% to 2.5%) for taurine and 3.6% (range, -2.6% to 8.8%) for carnitine. No substantial amount of contamination with mercury, arsenic, or selenium was found in any of the products. During disintegration testing, 1 of 5 taurine products and 5 of 8 carnitine products did not disintegrate within 45 minutes during at least 1 test. Disintegration time for those that did disintegrate ranged from 1.7 to 37.0 minutes. All product labels conformed with FDA regulations. Taurine and carnitine products evaluated in this study closely adhered to manufacturer claims and labeling guidelines. However, disintegration testing suggested high variability in some products, possibly limiting uptake and use by animals that receive them.

  7. Preparation of radioactive acetyl-l-carnitine by an enzymatic exchange reaction

    International Nuclear Information System (INIS)

    Emaus, R.; Bieber, L.L.

    1982-01-01

    A rapid method for the preparation of [1- 14 C]acetyl-L-carnitine is described. The method involves exchange of [1- 14 C]acetic acid into a pool of unlabeled acetyl-L-carnitine using the enzymes acetyl-CoA synthetase and carnitine acetyltransferase. After isotopic equilibrium is attained, radioactive acetylcarnitine is separated from the other reaction components by chromatography on Dowex 1 (C1 - ) anion exchange resin. One of the procedures used to verify the product [1- 14 C]acetyl-L-carnitine can be used to synthesize (3S)-[5- 14 C]citric acid

  8. Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

    Directory of Open Access Journals (Sweden)

    Tom L. Broderick

    2017-06-01

    Full Text Available Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH, organic cation transporter (OCTN2, and peroxisome proliferator-activated receptor (PPARα, a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

  9. L-carnitine protects against testicular dysfunction caused by gamma irradiation in mice.

    Science.gov (United States)

    Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Alkafafy, Mohamed; El-Shazly, Samir Ahmed

    2014-07-01

    This study was conducted on mice to evaluate the radioprotective role of L-carnitine against γ-ray irradiation-induced testicular damage. Adult male mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure period either in the absence and/or presence of L-carnitine at an i.p. dose of 10 mg/kg body weight/day. Results revealed that γ-rays irradiation suppressed the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine prior and throughout γ-rays irradiation exposure inhibited this suppression. Treatment with γ-ray irradiation or L-carnitine down-regulated expression of aromatase mRNA. With combined treatment, L-carnitine significantly normalized aromatase expression. γ-Ray irradiation up-regulated expression of FasL and Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also showed that γ-ray-irradiation up-regulated TNF-α, IL1-β and IFN-γ mRNA expressions compared to either controls or the L-carnitine treated group. Moreover, γ-irradiation greatly reduced serum testosterone levels, while L-carnitine, either alone or in combination with irradiation, significantly increased serum testosterone levels compared to controls. In addition, γ-irradiation induced high levels of sperm abnormalities (43%) which were decreased to 12% in the presence of L-carnitine. In parallel with these findings, histological examination showed that γ-irradiation induced severe tubular degenerative changes, which were reduced by L-carnitine pre-treatment. These results clarified the immunostimulatory effects of L-carnitine and its radioprotective role against testicular injury. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

    DEFF Research Database (Denmark)

    Vigerust, Natalya Filipchuk; Bohov, Pavol; Bjørndal, Bodil

    2012-01-01

    To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS).......To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS)....

  11. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Science.gov (United States)

    2010-04-01

    ..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

  12. The structure and organization of the human carnitine/acylcarnitine translocase (CACT1) gene2

    NARCIS (Netherlands)

    Iacobazzi, V.; Naglieri, M. A.; Stanley, C. A.; Wanders, R. J.; Palmieri, F.

    1998-01-01

    The carnitine/acylcarnitine translocase (CACT) transports acylcarnitines into mitochondria in exchange for free carnitine and it is, therefore, essential for the fatty acid beta-oxidation pathway. We have determined the exon-intron structure of the human CACT gene, which is responsible for a genetic

  13. The Effect of Acetyl-L-Carnitine Administration on Persons with Down Syndrome

    Science.gov (United States)

    Pueschel, Siegfried M.

    2006-01-01

    Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and…

  14. Aminocarnitine and acylaminocarnitines: Carnitine acyltransferase inhibitors affecting long-chain fatty acid and glucose metabolism

    International Nuclear Information System (INIS)

    Clark, D.J.

    1989-01-01

    DL-Aminocarnitine (DL-3-amino-4-trimethylaminobutyrate) and the acylaminocarnitines acetyl-, decanoyl- and palmitoyl-DL-aminocarnitine have been synthesized and tested as inhibitors of carnitine palmitoyl-transferase and carnitine acetyltransferase in vitro and in vivo. Acetyl-DL-aaminocarnitine is the most potent reversible inhibitor of carnitine acetyltransferase reported to date, and is competitive with respect to acetyl-L-carnitine. Mice given acetyl-DL-aminocarnitine metabolize [U- 14 C]acetyl-L-carnitine at about 60% of the rate of control mice. Palmitoyl-DL-aminocarnitine is the most potent reversible inhibitor of carnitine palmitoyltransferase reported to date. Decanoyl-DL-aminocarnitine and DL-aminocarnitine are also very potent inhibitors; all compounds inhibit the catabolism of [ 14 C]palmitate to 14 CO 2 in intact mice by at least 50%. Carnitine palmitoyltransferase controls the entry of long-chain fatty acids into the mitochondrial matrix for β-oxidation. The inhibition of carnitine palmitoyltransferase by aminocarnitine or acylaminocarnitines in vivo prevents or reverses ketogenesis in fasted mice, and causes the reversible accumulation of triglycerides in liver, kidney and plasma. Administration of DL-aminocarnitine to streptozotocindiabetic mice lowers plasma glucose levels and improves the glucose tolerance test

  15. L-Carnitine Supplementation Improves the Behavioral Symptoms in Autistic Children

    Science.gov (United States)

    Fahmy, Sarah Farid; El-hamamsy, Manal H.; Zaki, Osama K.; Badary, Osama A.

    2013-01-01

    L-Carnitine was proposed as a potential treatment for patients diagnosed with autism to ameliorate the behavioral symptoms associated with the disease. Thirty children diagnosed with autism were randomly assigned to receive (100 mg/kg bodyweight/day) of liquid L-carnitine (n = 16) or placebo (n = 14) for 6 months. Measurements included changes in…

  16. Effects of vitamin C and L-carnitine on lipid profile and oxidative ...

    African Journals Online (AJOL)

    The roles of vitamin C and L-carnitine on lipid profile and oxidative stress parameters in the brain of rats during fasting and re-feeding were investigated. Sixty male Sprague-Dawley rats (170-180 g) were divided into four groups of control, fasting, fasting + vitamin C and fasting + L-carnitine. The test groups were further ...

  17. Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Fujisawa, Koichi; Takami, Taro; Fukui, Yumi; Quintanilha, Luiz Fernando; Matsumoto, Toshihiko; Yamamoto, Naoki; Sakaida, Isao

    2017-05-01

    Mesenchymal stem cells (MSCs) are multipotent cells showing potential for use in regenerative medicine. Culture techniques that are more stable and methods for the more efficient production of MSCs with therapeutic efficacy are needed. We evaluate the effects of growing bone marrow (Bm)-derived MSCs in the presence of L-carnitine, which is believed to promote lipid metabolism and to suppress apoptosis. The presence of L-carnitine decreased the degree of drug-induced apoptosis and suppressed adipogenic differentiation. Metabolomic analysis by means of the exhaustive investigation of metabolic products showed that, in addition to increased β-oxidation and the expression of all carnitine derivatives other than deoxycarnitine (an intermediate in carnitine synthesis), polysaturated and polyunsaturated acids were down-regulated. An integrated analysis incorporating both serial analysis of gene expression and metabolomics revealed increases in cell survival, suggesting the utility of carnitine. The addition of carnitine elevated the oxygen consumption rate by BmMSCs that had been cultured for only a few generations and those that had become senescent following repeated replication indicating that mitochondrial activation occurred. Our exhaustive analysis of the effects of various carnitine metabolites thus suggests that the addition of L-carnitine to BmMSCs during expansion enables efficient cell production.

  18. Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Malone Michael A

    2006-01-01

    Full Text Available Abstract Background Streptozotocin-induced diabetes (STZ-D in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. Aim The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. Methods Wistar rats (48 were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24 were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. Results The heart rates for the STZ-D rats (290 ± 19 bpm were less than control rats (324 ± 20 bpm (p Conclusion Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

  19. EVALUATING THE EFFECTIVENESS OF ELKAR (L-CARNITINE IN PREMATURE INFANTS

    Directory of Open Access Journals (Sweden)

    Svetlana V. Garina

    2016-06-01

    Full Text Available Introduction. Recently in Russia there is a tendency to increase the proportion of premature infants, prolonged postnatal adaptation which may be associated with carnitine deficiency Early diagnosis and correction of carnitine deficiency in premature infants is possible to reserve the prevention of pathological conditions of the prenatal period in these patients. Materials and Methods. 98 newborn infants have been examined with the help of clinical laboratory methods. Results. It has been stated that the overwhelming majority of newborn infants irrespective of their gestational age and body mass at the moment of birth had reference ranges of crude carnitine and higher degree of floating carnitine in their peripheral blood within the first days of their lives. These changes are particularly characteristic for small pre-mature infants. Statistically significant differences between the levels of crude carnitine and floating carnitine depended on the gender of newborn infants have been revealed. Directly correlated dependence of the level of crude carnitine on the body mass at the moment of birth of small premature infants has been stated. Discussion and Conclusions. It has been proved that implementing L-carnitine into the development care plan for premature infants facilitates quick body weight gain, significantly cuts down the period of tube feeding, lowers frequency of anemia development of premature infants and duration of neonatal jaundice. The ability of Elkar to correct functional diseases of cardio vascular system of premature infants has been shown.

  20. L-carnitine increases body lean in adult dogs and cats

    OpenAIRE

    Jewell, D.

    2010-01-01

    L-carnitine has been shown to be a repartitioning agent (i.e.,setting metabolism toward more protein and less fat accretion) in animals used for food production. The purpose of this study was to determine the effects on body composition repartitioning (i.e.,increasing lean body mass) of added dietary L-carnitine in adult dogs and cats.

  1. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

    Directory of Open Access Journals (Sweden)

    Adriana Cristofano

    Full Text Available This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L to subjective memory complaint (4.3±0.9 μmol/L, mild cognitive impairment (4.0±0.53 μmol/L, up to Alzheimer's disease (3.5±0.6 μmol/L group (p<0.001. The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  2. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia

    Science.gov (United States)

    Sapere, Nadia; La Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Corbi, Graziamaria; Scapagnini, Giovanni; Intrieri, Mariano; Russo, Claudio

    2016-01-01

    This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  3. Activity of D-carnitine and its derivatives on Trypanosoma infections in rats and mice

    Directory of Open Access Journals (Sweden)

    Manganaro M.

    2003-06-01

    Full Text Available Little progress has been made in the treatment of African trypanosomiasis over the past decades. L-carnitine has a major role in glycolysis-based energy supply of blood trypanosomes for it stimulates constant ATP production. To investigate whether administration of the isomer D-carnitine could exert a competitive inhibition on the metabolic pathway of the L-form, possibily resulting in parasite replication inhibition, several formulations of this compound were tested on Trypanosoma lewisi and T. brucei rhodesiense in rodent models. High oral dosages of D-carnitine inner salt and proprionyl-D-carnitine were not toxic to animals and induced about 50 % parasite growth inhibition in reversible, i.e. competitive, fashion. A putative mechanism could be an interference in pyruvate kinase activity and hence ATP production. Considering both, lack of toxicity and inhibitory activity, D-carnitine may have a role in the treatment of African trypanosomiasis, in association with available trypanocidal drugs.

  4. The antidiabetic effect of L-carnitine in rats: the role of nitric oxide system

    Directory of Open Access Journals (Sweden)

    Shaghayegh Hajian-Shahri

    2017-11-01

    Full Text Available Background: Nowadays, the use of L-carnitine in the treatment of diabetes is increasing. This study was conducted to investigate the effect of co-administration of L-arginine (precursor for the synthesis of nitric oxide and nitro-L-arginine (nitric oxide synthesis inhibitor on antidiabetic activity of L-carnitine in diabetic rats. Materials and Methods: In this study, 50 male rats weighing 180-201g were divided into five groups: (1 non diabetic control rats; (2 untreated diabetic rats; (3 diabetic rats treated with L-carnitine 300 mg/kg (4; diabetic rats treated with L-carnitine 300 mg/kg + L-arginine 300 mg/kg; and (5 diabetic rats treated with L-carnitine (300 mg/kg + nitro-L-arginine (1mg/kg. Type 1 diabetes was induced by a single intraperitoneal injection of 110 mg/kg body weight alloxan. After 30 days, liver malondialdehyde levels, lipid profile, serum glucose, and glycated hemoglobin serum levels were measured. Results: Blood glucose, liver enzymes, glycated hemoglobin, and liver malondialdehyde levels significantly decreased in diabetic rats treated with L-carnitine compared to the untreated diabetic group (P<0.05. The co-administration of L-arginine and L-carnitine led to a significant decrease in glycated hemoglobin levels and serum glucose, in a manner similar to the group received only L-carnitine. Also, L-arginine and nitro-l-arginine had similar effects on liver lipid peroxidation and serum biochemical parameters. Conclusion: The results suggest that the hypoglycemic effect of L-carnitine is mediated independently from nitric oxide pathways. The interaction between L-carnitine and L-arginine may not be synergistic. So, their combined administration is not recommended for the diabetic patients.

  5. Fenofibrate Therapy in Carnitine Palmitoyl Transferase Type 2 Deficiency

    Directory of Open Access Journals (Sweden)

    I. Hamilton-Craig

    2012-01-01

    Full Text Available Bezafibrate therapy has been shown to improve beta-oxidation of fatty acids and to reduce episodes of rhabdomyolysis in patients with carnitine palmitoyltransferase type-2 (CPT2 deficiency. We report the efficacy of fenofibrate in a patient with CPT2 deficiency, in whom beta-oxidation was improved but an episode of rhabdomyolysis nevertheless occurred. This suggests additional methods to avoid rhabdomyolysis in patients with CPT2 deficiency should accompany fibrate therapy, including avoidance of muscular overexertion, dehydration, and heat exposure.

  6. Synthesis of [methyl-14C]crotonobetaine from DL-[methyl-14C]carnitine

    International Nuclear Information System (INIS)

    Loester, H.; Seim, H.

    1996-01-01

    The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to γ-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring γ-betaines - L-carnitine, crotonobetaine, γ-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or γ-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl- 14 C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl- 14 C]crotonobetaine (yield about 50 %), [methyl- 14 C]glycine betaine and [methyl- 14 C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author)

  7. Update on critical evidence for use of carnitine analogs in clinical practice in CNS disorders

    Directory of Open Access Journals (Sweden)

    Traina G

    2011-04-01

    Full Text Available Giovanna TrainaDepartment of Economics and Food Sciences, University of Perugia, Perugia, ItalyAbstract: L-carnitine (LC is part of the carnitine shuttle system at the mitochondrial inner membrane (MIM and transports long chain fatty acids over the MIM route. Acetyl-L -carnitine (ALC, the acetyl ester of LC, plays an essential role in intermediary metabolism. To ALC are ascribed neurotrophic actions, antioxidant and antiapoptotic activity, positive effects on mitochondrial metabolism, and stabilization of intracellular membranes. Acylcarnitine and LC supplementation have shown beneficial effects in the treatment of aging, chronic degenerative pathologies and the slowing of the progression of mental deterioration in neurodegenerative diseases, and painful neuropathies. ALC is reported to affect brain energy and phospholipid metabolism and to interact with cell membranes, proteins, and enzymes. It also shows a neuromodulatory effect on synaptic morphology and neurotransmitter synaptic transmission, including that of acetylcholine and dopamine. All these data suggest that ALC can affect several targets in the central nervous system. The roles and effects of LC and ALC have led researchers to investigate carnitine's involvement in a variety of neuropathological states and treatments, including autism, Parkinson's disease, Alzheimer's disease, Down's syndrome, Huntington's disease, cerebellar ataxia, age-associated mental decline, hepatic encephalopathy, and ammonia neurotoxicity. This review summarizes evidence that carnitine analogs play many roles in serious neurological pathologies.Keywords: L-carnitine, acetyl-L-carnitine, brain, neural disorders

  8. Does left ventricular function improve with L-carnitine after acute myocardial infarction?

    Directory of Open Access Journals (Sweden)

    Iyer R

    1999-04-01

    Full Text Available A double blind randomized placebo controlled clinical trial was carried out to assess the efficacy and safety of L-carnitine in patients suffering from acute anterior wall myocardial infarction with respect to left ventricular function. Sixty patients (34 men, 26 women, mean age 56+11 yr. with acute anterior wall myocardial infarction were randomized to placebo and L-carnitine. All the patients were given intravenous L-carnitine / placebo in the dose of 6gm/day for the first seven days followed by oral L-carnitine / placebo 3 gm/day in three divided doses for a period of three months. Echocardiography was performed for regional wall motion abnormality, left ventricular end systolic volume (ESV, end diastolic volume (EDV and ejection fraction (EF on admission, after seven days and after three months of the infarction. Forty-four patients completed the study. There were three deaths, two in the placebo and one in the L-carnitine group (p>0.05. Thirteen patients were lost to follow up. Echo parameters in both groups were comparable (p>0.05. The duration of chest pain prior to initiation of the I.V. L-carnitine was 7.5 + 5.2 hrs in the L-carnitine group and 7 + 4 hrs in the placebo group (p>0.05. There was no statistical difference in the EF, ESV and EDV on admission, at discharge and after three months in the L-carnitine and the placebo groups (p>0.05. No significant adverse effects were noted. L-carnitine, though a safe drug, does not affect the left ventricular function in patients with myocardial infarction.

  9. L-carnitine: a partner between immune response and lipid metabolism ?

    Directory of Open Access Journals (Sweden)

    Giuseppe Famularo

    1993-01-01

    Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

  10. Synthesis of O-[11C]acetyl CoA, O-[11C]acetyl-L-carnitine, and L-[11C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    International Nuclear Information System (INIS)

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-01-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with 11 C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1- 11 C]acetyl CoA and O-[2- 11 C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1- 11 C]acetyl-L-carnitine and O-[2- 11 C]acetyl-L-carnitine in 70-80% yield, based on [1- 11 C]acetate or [2- 11 C]acetate, respectively. By an N-methylation reaction with [ 11 C]methyl iodide, L-[methyl- 11 C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl- 11 C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [ 11 C]methyl iodide. Initial data of the kinetics of the different 11 C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented

  11. Synthesis of O-[{sup 11}C]acetyl CoA, O-[{sup 11}C]acetyl-L-carnitine, and L-[{sup 11}C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-07-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with {sup 11}C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-{sup 11}C]acetyl CoA and O-[2-{sup 11}C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-{sup 11}C]acetyl-L-carnitine and O-[2-{sup 11}C]acetyl-L-carnitine in 70-80% yield, based on [1-{sup 11}C]acetate or [2-{sup 11}C]acetate, respectively. By an N-methylation reaction with [{sup 11}C]methyl iodide, L-[methyl-{sup 11}C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-{sup 11}C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [{sup 11}C]methyl iodide. Initial data of the kinetics of the different {sup 11}C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented.

  12. Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

    Directory of Open Access Journals (Sweden)

    Abeer Hassan

    2015-01-01

    Full Text Available Transarterial chemoembolization (TACE is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P<0.01. Conversely, the control group reported a significant CP score deterioration at 1 week (P<0.05 and 12 weeks after TACE (P<0.05. L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P<0.05 and 4 weeks after TACE (P<0.05. L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P<0.05, and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P<0.05. The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE.

  13. [Therapy of arrhythmia induced by myocardial ischemia. Association of L-carnitine, propafenone and mexiletine].

    Science.gov (United States)

    Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L; Campolo, M A; Agricola, E; Palazzuoli, V

    1995-12-01

    To assess the anti-arrythmic effect of L-carnitina, propafenone and mexiletine, we tested the drugs in 50 patients with effort angina and ventricular ectopic beats (VEB). The patients were randomized in 5 groups: Group A: was treated with oral L-carnitine at the dose of 2 g x 3 for two weeks. Group B: oral propafenone at the dose of 300 mg x 3 for two weeks. Group C: as group B+L-carnitine+g x 3 at the second weeks. Group D: oral mexiletine at the dose of 200 mg x 3 for two weeks. Group E: as group D+L-carnitine 2 gr x 3 at the second week. After 7 and 14 days of treatment, in all patients an Holter examination was performed. Our results show that L-carnitine exerts a significant reduction of the VEB and its administration potentiates the anti-arrythmic effect of propafenone and mexiletine.

  14. Ameliorative effects of l-carnitine on rats raised on a diet supplemented with lead acetate

    Directory of Open Access Journals (Sweden)

    El-Said El-Sherbini

    2017-09-01

    Conclusion:l-Carnitine may play an important role in reversing the undesirable effects of lead intoxication. Future studies should be conducted to see whether such an effect is applicable in humans exposed to lead poising.

  15. Impaired exercise performance and skeletal muscle mitochondrial function in rats with secondary carnitine deficiency

    Directory of Open Access Journals (Sweden)

    Jamal BOUITBIR

    2016-08-01

    Full Text Available Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP, a carnitine analogue inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats.Methods: Male Sprague Dawley rats were treated daily with water (control rats; n=12 or with 20 mg/100 g body weight THP (n=12 via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion.Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24% and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected.Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle.

  16. Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

    Directory of Open Access Journals (Sweden)

    Richard D. Semba

    2017-03-01

    Interpretation: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

  17. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

    Directory of Open Access Journals (Sweden)

    Luciana P. Rodrigues

    2010-01-01

    Full Text Available AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein-calorie restriction with free access to water (malnutrition group and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group were studied. After the undernourishment period (4 weeks with or without alcohol, both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage (carnitine groups. No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P.05 was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

  18. [The hypotriglyceridemic action of the combination of L-carnitine + simvastatin vs. L-carnitine and vs. simvastatin].

    Science.gov (United States)

    Savica, V; Bellinghieri, G; Lamanna, F

    1992-01-01

    Previous studies had determined the role played by L-carnitine and simvastatin in the treatment of altered lipidemia in dialyzed patients with chronic uremia. The authors carried out a study on the above substances either singly or together administered to the same patients with chronic uremia in hemodialysis. This study was aimed at demonstrating the possible synergic normolipidemic action of both substances in comparison with their single administration, because their different mechanism of action could be metabolically enhanced. The obtained results demonstrated that the therapeutic association proposed is preferable to the use of the single substances. Moreover, a higher and more rapid normolipidemic effect was obtained after using L-carnitina associated with simvastatin with respect to the separated substances.

  19. Comparison of plasma, liver, and skeletal muscle carnitine concentrations in cats with idiopathic hepatic lipidosis and in healthy cats.

    Science.gov (United States)

    Jacobs, G; Cornelius, L; Keene, B; Rakich, P; Shug, A

    1990-09-01

    Concentrations of total, free, and esterified carnitine were determined in plasma, liver, and skeletal muscle from cats with idiopathic hepatic lipidosis and compared with values from healthy cats. The mean concentrations of plasma, liver, and skeletal muscle total carnitine; plasma and skeletal muscle free carnitine; and plasma and liver esterified carnitine were greater (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. The mean for the ratio of free/total carnitine in plasma and liver was lower (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. These data suggest that carnitine deficiency does not contribute to the pathogenesis of feline idiopathic hepatic lipidosis.

  20. Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine

    OpenAIRE

    H.D. Vallance; A. Koochin; J. Branov; A. Rosen-Heath; T. Bosdet; Z. Wang; S.L. Hazen; G. Horvath

    2018-01-01

    Oral supplementation with l-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of l-carnitine, trimethylamine oxide (TMAO), is an independent and dose-dependent risk factor for cardiovascular disease (CVD). Given the limited data demonstrating efficacy with oral l-carnitine therapy and the newly raised questions of potential harm, we assessed pla...

  1. Synthesis and biological evaluation of cyclic analogs of L-carnitine as potential agents in the treatment of myocardial ischemia

    International Nuclear Information System (INIS)

    Woster, P.M.

    1987-01-01

    The purpose of this research was to synthesize a number of cyclic, rigid analogs of L-carnitine, having a variety of predetermined positional and stereochemical orientations, to be used as probes into the spatial and conformational requirements of the enzyme known as carnitine/acylcarnitine translocase. The ability of these analogs to serve as substrates for this enzyme was to be determined by assessing the degree to which they initiate efflux of 14 C-L-carnitine from isolated heart mitochondria. Toward this end, synthesis of several such analogs was attempted, resulting in the isolation and characterization of 9 cyclic analogs of carnitine, 5 of which are previously unreported. Bioevaluation of these synthetic carnitine analogs was conducted in a previously described assay system. Rat heart mitochondria were isolated by differential centrifugation and prepared for the study by incubation with 14 C-L-carnitine. Efflux of radiolabeled carnitine was then monitored in the presence of the compound being evaluated. This represents the first instance in which non-naturally occurring analogs of L-carnitine have been shown to undergo transport via this mitochondrial translocase, suggesting the possibility that cyclic carnitine analogs may find utility as agents in the treatment of myocardial ischemia

  2. Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

    Science.gov (United States)

    Rau, Thomas F.; Lu, Qing; Sharma, Shruti; Sun, Xutong; Leary, Gregory; Beckman, Matthew L.; Hou, Yali; Wainwright, Mark S.; Kavanaugh, Michael; Poulsen, David J.; Black, Stephen M.

    2012-01-01

    Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD. PMID:22984394

  3. Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

    Directory of Open Access Journals (Sweden)

    Yu Cao

    2013-03-01

    Full Text Available The urine excretion of L-carnitine (LC, acetyl-L-carnitine (ALC and propionyl-Lcarnitine (PLC and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD, total antioxidative capacity (T-AOC, malondialdehyde (MDA and nitrogen monoxidum (NO activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277 or T-AOC (r = 0.9547, and a negative correlation was found between urine LC excretions and NO (r = -0.8575 or MDA (r = 0.7085. In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.A excreção urinária de L-carnitina (LC, acetil-L-carnitina (ALC e propionil-L-carnitine (PLC e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentra

  4. In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

  5. Effect of different levels of L-carnitine and lysine-methionine on broiler blood parameters

    Directory of Open Access Journals (Sweden)

    Babak Hosseintabar

    2015-09-01

    Full Text Available Objetive. In the present study a completely randomized 3×3 factorial design was used to analyze the effects of different levels of L-Carnitine, lysine(Lys and methionine (Met on the blood concentrations of energy, protein and lipid metabolites of male broiler chickens. Materials and methods. A total of 270 newly hatched male broiler chickens (Ross 308 were randomly assigned to 9 groups (ten broilers per replicate and three replicates per treatment. The control group was fed a basal diet, whereas the treatment groups were fed basal diets supplemented with L-Carnitine (0 mg/kg, 75 mg/kg and 150 mg/kg and lysine-methionine (0, 15 and 30% for 42 days. On day 42, one bird was randomly chosen per replication, a blood sample was taken and the blood concentrations of glucose (GLU, uric acid (UAc, triglyceride (TG, VLDL, HDL, LDL, total protein (TP, albumin (Alb and total cholesterol (TC were analyzed. Results. Dietary L-carnitine supplementation had a significant effect (p<0.05 on uric acid (UAc, HDL, LDL, and total cholesterol (TC. The birds feed L-carnitine plus Lys and Met presented the highest plasmatic UAc level and the lowest plasmatic TC and LDL level. Moreover, L-carnitine significantly reduced total cholesterol (TC when compared with both the control group and the birds feed Lys and Met without L-carnitine. Conclusions. A diet with 150 mg/kg L-carnitine plus 15% Lys and Met seems to be enough to sustain low plasmatic TC, LDL and HDL concentrations on male broiler.

  6. [Study of aerobic capacity in chronic hemodialized patients: effect of L-carnitine supplementation].

    Science.gov (United States)

    Pacheco, Alejandro; Torres, Rubén; Sanhueza, María Eugenia; Elgueta, Leticia; Segovia, Erico; Cano, Marcelo

    2008-04-05

    Chronic hemodialyzed patients have a low level of aerobic capacity, caused by the pathologies concomitant to renal insufficiency, according with a low level of physical activity. One of the factors that would contribute to this level of aerobic capacity is the L-carnitine deficit on skeletal muscle. However, the value of the supplementation of L-carnitine to improve the physical fitness has been controversial. The objective of this work was to evaluate the effect of the administration of L-carnitine on VO2 max in hemodialyzed patients. A group of 21 patients (20-50 years old) on a program of chronic hemodialysis was studied. During 12 weeks, 13 of them received L-carnitine, 7 men and 6 women, 38.8 (9.5) years old; BMI 24.2 (2.1) Kg/m2; 8 of them received placebo, 4 men and 4 women, 35.8 (11.4) years old; BMI 24.5 (5.8) Kg/m2. There was an increase in VO2 peak on L-carnitine group from 16.3 (2.8) mL x Kg(-1) x min(-1) to 19.5 (3.3) mL x Kg(-1) x min(-1), and the same was seen in the placebo group (increase in VO2 peak from 14.8 (3.8) mL x Kg(-1) x min(-1) to 18.9 (4.8) mL x Kg(-1) x min(-1)). The L-carnitine and placebo groups did not show statistical differences at the end of this study (all values above p > 0.05). In this group of patients, the intravenous supplementation of L-carnitine during 12 weeks did not have an impact on the improvement of the VO2 peak.

  7. Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria

    International Nuclear Information System (INIS)

    Lamhonwah, Anne-Marie; Tein, Ingrid

    2006-01-01

    Carnitine is a zwitterion essential for the β-oxidation of fatty acids. We report novel localization of the organic cation/carnitine transporter, OCTN1, to mitochondria. We made GFP- and RFP-human OCTN1 cDNA constructs and showed expression of hOCTN1 in several transfected mammalian cell lines. Immunostaining of GFP-hOCTN1 transfected cells with different intracellular markers and confocal fluorescent microscopy demonstrated mitochondrial expression of OCTN1. There was striking co-localization of an RFP-hOCTN1 fusion protein and a mitochondrial-GFP marker construct in transfected MEF-3T3 and no co-localization of GFP-hOCTN1 in transfected human skin fibroblasts with other intracellular markers. L-[ 3 H]Carnitine uptake in freshly isolated mitochondria of GFP-hOCTN1 transfected HepG2 demonstrated a K m of 422 μM and Western blot with an anti-GFP antibody identified the expected GFP-hOCTN1 fusion protein (90 kDa). We showed endogenous expression of native OCTN1 in HepG2 mitochondria with anti-GST-hOCTN1 antibody. Further, we definitively confirmed intact L-[ 3 H]carnitine uptake (K m 1324 μM), solely attributable to OCTN1, in isolated mitochondria of mutant human skin fibroblasts having <1% of carnitine acylcarnitine translocase activity (alternate mitochondrial carnitine transporter). This mitochondrial localization was confirmed by TEM of murine heart incubated with highly specific rabbit anti-GST-hOCTN1 antibody and immunogold labeled goat anti-rabbit antibody. This suggests an important yet different role for OCTN1 from other OCTN family members in intracellular carnitine homeostasis

  8. Gender differences in locomotor and stereotypic behavior associated with l-carnitine treatment in mice.

    Science.gov (United States)

    Benvenga, Salvatore; Itri, Elenora; Hauser, Peter; De Tolla, Louis; Yu, Sui-Foh; Testa, Giuseppe; Pappalardo, Maria Angela; Trimarchi, Francesco; Amato, Antonino

    2011-02-01

    The carnitines exert neuroprotective and neuromodulatory actions, and carnitine supplementation increases locomotor activity (LMA) in experimental animals. We measured 13 indexes of LMA and 3 indexes of stereotypic activity (STA) in adult male and female caged mice. In a randomized 4-week trial, 10 males and 10 females received 50 mg/kg body weight PO l-carnitine, and another 10 males and 10 females received placebo. Compared with placebo-treated females, placebo-treated males had a greater number of stereotypies (NSTs), stereotypy counts (STCs), stereotypy time (STT), and right front time (RFT), but smaller total distance traveled (TDT), margin distance (MD), number of vertical movements (NVMs), and left rear time (LRT). Compared with placebo-treated males, carnitine-treated males had greater horizontal activity (HA), movement time (MT), NVM, STT, TDT, STC, MD, LRT, and clockwise revolutions (CRs), but smaller left front time (LFT) and RFT. Compared with placebo-treated females, carnitine-treated females had greater NST, STC, STT, LFT, and RFT, but smaller NM, HA, NVM, VA, MT, anticlockwise revolutions (ACRs), CR, TDT, and MD; right rear time (RRT) remained statistically insignificant across all comparisons. In summary, l-carnitine caused gender differences to persist for STC, diminish for NST and STT, disappear for LRT and NVM, change in the opposite direction for TDT and MD, appear de novo for HA, VA, NM, MT, and LFT, and remain absent for RRT and ACR. Some indexes of LMA and STA are sexually dimorphic in adult mice, and l-carnitine differentially maintains, diminishes/cancels, inverts, or creates the sexual dimorphism of particular indexes. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  9. Ameliorative effects of l-carnitine on rats raised on a diet supplemented with lead acetate.

    Science.gov (United States)

    El-Sherbini, El-Said; El-Sayed, Gehad; El Shotory, Rehab; Gheith, Nervana; Abou-Alsoud, Mohamed; Harakeh, Steve Mustapha; Karrouf, Gamal I

    2017-09-01

    Lead intoxication has been a major health hazard in humans. It affects people at all ages. Its toxicity is associated with various organs of the body and affects different metabolic pathways. Based on histological data, l-carnitine reduced the severity of tissue damage produced as a result of exposure of rats to lead acetate. The main objective of this study was to evaluate the underlying mechanism of protection offered by l-carnitine against lead acetate intoxication using male Sprague-Dawley rats. Forty male Sprague-Dawley rats were randomly divided into four groups with ten rats in each. The first group (G1) served as the control group and animals received standard diet only. The second group (G2) received lead acetate in their diet. The third group (G3) was the l-carnitine treated group and received the normal standard diet supplemented with l-carnitine. While the fourth group (G4) had a diet supplemented with both lead acetate and l-carnitine. At the end of each experiment, blood (serum and whole blood) were collected from each animal and analyzed for the following parameters: serum testosterone levels, serum nitric oxide and serum malondialdehyde. This is in addition to looking at the enzymatic activities of two important enzymes (superoxide dismutase and catalase) and on (glutathione reductase) which are indicative of the antioxidant activities in the whole blood. The results indicated that l-carnitine will counteract the undesirable effects of lead intoxication. It exerted its antioxidant potential by reducing the production of ROS and scavenging free radicals by maintaining and protecting the level of the of antioxidant enzymes SOD, CAT and glutathione peroxidase. Conclusion: l-Carnitine may play an important role in reversing the undesirable effects of lead intoxication. Future studies should be conducted to see whether such an effect is applicable in humans exposed to lead poising.

  10. Effects of exercise on l-carnitine and lipid metabolism in African catfish (Clarias gariepinus) fed different dietary l-carnitine and lipid levels

    NARCIS (Netherlands)

    Ozorio, R.O.A.; Ginneken, van V.J.T.; Bessa, R.J.B.; Verstegen, M.W.A.; Verreth, J.A.J.; Huisman, E.A.

    2010-01-01

    African catfish (Clarias gariepinus) were fed four isonitrogenous diets (34 % crude protein), each containing one of two lipid (100 or 180 g/kg) and two l-carnitine (15 or 1000 mg/kg) levels. After 81 d of feeding, thirty-two fish (body weight 32 g) from each dietary group were randomly selected,

  11. Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA).

    Science.gov (United States)

    Genazzani, Alessandro D; Despini, Giulia; Czyzyk, Adam; Podfigurna, Agnieszka; Simoncini, Tommaso; Meczekalski, Blazej

    2017-12-01

    Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

  12. Molecular analysis of carnitine palmitoyltransferase II deficiency with hepatocardiomuscular expression

    Energy Technology Data Exchange (ETDEWEB)

    Bonnefont, J.P.; Cepanec, C.; Leroux, J.P. [Unite INSERM, Paris (France)] [and others

    1996-05-01

    Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical act phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibility of this mutation for the disease. Metabolic consequences of the Ser-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, without consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency. 32 refs., 5 figs.

  13. Effect of dietary lipid, carnitine and exercise on lipid profile in rat blood, liver and muscle.

    Science.gov (United States)

    Karanth, Jyothsna; Jeevaratnam, K

    2009-09-01

    Aim of this study was to investigate the influence of physical exercise on effects of the daily intake of vegetarian diet of either vegetable hydrogenated fat (HF) or peanut oil (PO) with or without carnitine on the lipid profile. Eight groups of male Wistar rats were fed HF-diet (4 groups) or PO-diet (4 groups), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. Plasma triglycerides (TG), total cholesterol (TC), HDL-cholesterol, free fatty acids (FFA), liver and thigh muscle glycogen, total fat (TF), TG, TC and FFA were analyzed. HF-fed rats showed significantly increased plasma TC, VLDL+LDL-cholesterol and TG compared to PO-fed rats, wherein a lowered plasma TC, TG levels in all the groups with significantly increased liver cholesterol and decreased muscle cholesterol was observed. Physical exercise of moderate intensity reduced plasma TC and TG accompanied by significantly reduced tissue TG and cholesterol while FFA and glycogen increased in all the groups. The influence of exercise was less pronounced in carnitine supplemented rats since carnitine could significantly reduce TG in plasma and tissues of sedentary rats. Results from the present study showed that the intake of HF diet significantly increased the plasma and tissue lipid profile and MUFA-rich diet or carnitine supplementation and/or exercise may ameliorate the deleterious effects of HF.

  14. Crystal Structures of Murine Carnitine Acetyltransferase in Ternary Complexes with Its Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Hsiao,Y.; Jogl, G.; Tong, L.

    2006-01-01

    Carnitine acyltransferases catalyze the reversible exchange of acyl groups between coenzyme A (CoA) and carnitine. They have important roles in many cellular processes, especially the oxidation of long-chain fatty acids in the mitochondria for energy production, and are attractive targets for drug discovery against diabetes and obesity. To help define in molecular detail the catalytic mechanism of these enzymes, we report here the high resolution crystal structure of wild-type murine carnitine acetyltransferase (CrAT) in a ternary complex with its substrates acetyl-CoA and carnitine, and the structure of the S554A/M564G double mutant in a ternary complex with the substrates CoA and hexanoylcarnitine. Detailed analyses suggest that these structures may be good mimics for the Michaelis complexes for the forward and reverse reactions of the enzyme, representing the first time that such complexes of CrAT have been studied in molecular detail. The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general.

  15. Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes

    NARCIS (Netherlands)

    I.M. Garrelds (Ingrid); G.R. Elliott (G.); F.J. Zijlstra (Freek); I.L. Bonta

    1994-01-01

    textabstractThe effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids front in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A

  16. Effect of short- and long-term feeding of L-carnitine and its congeners on the production of eicosanoids from rat peritoneal leukocytes

    NARCIS (Netherlands)

    Garrelds, I.M.; Elliott, G.R.; Zijlstra, F.; Bonta, I.

    1994-01-01

    The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number

  17. Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish.

    Science.gov (United States)

    Li, Jia-Min; Li, Ling-Yu; Qin, Xuan; Degrace, Pascal; Demizieux, Laurent; Limbu, Samwel M; Wang, Xin; Zhang, Mei-Ling; Li, Dong-Liang; Du, Zhen-Yu

    2018-01-01

    Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW)/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG) concentrations, fatty acid (FA) β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin ( mtor ), and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model could also be

  18. Sibutramine and L-carnitine compared to sibutramine alone on insulin resistance in diabetic patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

    2010-01-01

    To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight, glycemic control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) >8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). There was a decrease in body weight, BMI, HbA(1c), FPI, HOMA-IR, and RBP-4 in both groups, even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group. There was a faster decrease of FPG, PPG, TC, LDL-C, resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained. Furthermore, only sibutramine plus L-carnitine improved Tg, and visfatin. Sibutramine plus L-carnitine gave a faster improvement of lipid profile, insulin resistance parameters, glycemic control, and body weight compared to sibutramine.

  19. Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish

    Directory of Open Access Journals (Sweden)

    Jia-Min Li

    2018-05-01

    Full Text Available Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG concentrations, fatty acid (FA β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin (mtor, and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model

  20. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    International Nuclear Information System (INIS)

    Deusing, Dorothé Jenni; Beyrer, Melanie; Fitzenberger, Elena; Wenzel, Uwe

    2015-01-01

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation

  1. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    Energy Technology Data Exchange (ETDEWEB)

    Deusing, Dorothé Jenni, E-mail: Dorothe.J.Deusing@ernaehrung.uni-giessen.de; Beyrer, Melanie, E-mail: m.beyrer@web.de; Fitzenberger, Elena, E-mail: Elena.Fitzenberger@ernaehrung.uni-giessen.de; Wenzel, Uwe, E-mail: uwe.wenzel@ernaehrung.uni-giessen.de

    2015-05-08

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

  2. L-Carnitine Ameliorates Immunological-induced Hepatitis in rats

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2006-01-01

    Immunological mediated hepatitis can be initiated by bacterial product; Lipopolysaccharide (LPS). The later is increased during severe infection, bacterial overgrowth or translocation. LPS stimulates Kupffer cells. Activation of the kupffer cells contributes to the onset of liver injuries by producing and releasing cytotoxic agents, inflammatory cytokines and reactive oxygen species. In the present study, L-carnitine, a natural antioxidant and immunoprotective agent, is used to protect against LPS-induced hepatitis. Liver content of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and the DNA adduct 8-hydroxydeoxyguanosine (8-HDG) are estimated. Serum activity of liver enzymes ALT, AST, and Gamma-GT, in addition to IL2 level are also estimated. Moreover, liver histopathological changes are determined. Results revealed that LPS (5mg/kg once i.p) significantly increased 8-HDG, MDA, NO and depleted GSH in the liver of the treated rats. It also increased serum IL2 and activity of all the estimated liver enzyme markers indicating massive hepatic cellular damage as also shown as a necrotic damage in liver histological sections. LCR administered (500mg/kg) 3h before LPS protected against LPS-induced lethality by 100%. LCR also prevented the increase in liver content of 8-HDG, MDA and NO. It reduced the depleted GSH and prevented the necrotic damage in the liver tissue as shown by normalization of ALT, AST and Gamma-Gt as well as IL2 and a remarkable improvement in liver histology. These data suggest that LCr could be used as an adjuvant therapy in severely infected and specific patients to counteract LPS-induced liver hepatitis. (author)

  3. Interaction of propionate and carnitine metabolism in isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Brass, E.P.; Beyerinck, R.A.

    1987-01-01

    Propionate (P) and its metabolic products P-CoA and methylmalonyl-CoA can disrupt normal hepatic metabolism. Carnitine (Cn) has been shown to partially restore cellular function in the presence of P. This effect of Cn may result from removal of propionyl groups as propionylcarnitine (P-Cn). The present study examined the kinetics of P-Cn formation in rat hepatocytes, and the consequence of P-Cn formation on P and Cn metabolism. 14 C-P was converted to CO 2 , glucose and P-Cn in the hepatocyte system. Increasing concentrations of Cn up to 10.0 mM increased P-Cn formation from P without affecting CO 2 or glucose formation. Thus, 10.0 mM Cn increased total P metabolism by 40%. Metabolism of P was associated with a decrease in Cn concentration and an increase in short chain acylcarnitines (SCCn). In the absence of added Cn, 60 min incubation with P decreased Cn from 6.8 to 2.5 μM with a corresponding increase in SCCn. This effect of P to deplete free Cn was not seen to the same degree with butyrate in place of P. Similar increases in the formation of SCCn in the presence of P at the expense of free Cn were seen when the incubation Cn concentration was increased to 50 μM or 150 μM. HPLC methodologies to study specific acylcarnitines demonstrated the accumulation of large amounts of P-Cn in the incubations containing P, accounting for the depletion of free Cn

  4. Carnitine acetyltransferase: A new player in skeletal muscle insulin resistance?

    Directory of Open Access Journals (Sweden)

    Sofia Mikkelsen Berg

    2017-03-01

    Full Text Available Carnitine acetyltransferase (CRAT deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16 and octadecanoylcarnitine (C18 were slightly reduced in myotubes derived from T2DM patients (p<0.05 compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

  5. L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia.

    Science.gov (United States)

    Szefel, Jarosław; Kruszewski, Wiesław Janusz; Ciesielski, Maciej; Szajewski, Mariusz; Kawecki, Krzysztof; Aleksandrowicz-Wrona, Ewa; Jankun, Jerzy; Lysiak-Szydłowska, Wiesława

    2012-07-01

    Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

  6. Radioiodinated fatty acid carnitine ester: synthesis and biodistribution of 15-(p-iodo[131I]-phenyl)pentadecanoyl-D,L-carnitine chloride

    International Nuclear Information System (INIS)

    Eisenhut, M.; Liefhold, J.

    1986-01-01

    After the uptake into heart muscle cells long chain fatty acids enter predominantly into the triglyceride and phospholipid pool before they are degraded in the mitochondria by β-oxidation. Therefore the formation of fatty acid esters with glycerine obscures the functional ability of the heart namely to catabolize free fatty acids. The sum of the two reaction pathways are visualized by sequential heart scintigraphy with e.g. 131 I labeled 15-(p-iodo-phenyl)-pentadecanoic acid (IPPA). Before the fatty acids can be degraded by β-oxidation they are bound to carnitine for mitochondrial membrane transport. Thus IPPA would not participate in lipid formation, if it is offered as 15-(p-iodo[ 131 I]-phenyl)-pentadecanoyl-D,L-carnitine chloride (IPPA-CE) to the heart muscle cells. Additionally carnitine esters of fatty acids are known to be better substrates for β-oxidation than free fatty acids. We were therefore interested in the biochemical fate of radioiodinated IPPA-CE in rats. (author)

  7. Synthesis of [methyl-{sup 14}C]crotonobetaine from DL-[methyl-{sup 14}C]carnitine

    Energy Technology Data Exchange (ETDEWEB)

    Loester, H.; Seim, H. [Leipzig Univ. (Germany). Inst. of Clinical Chemistry and Pathobiochemistry

    1996-02-01

    The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to {gamma}-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring {gamma}-betaines - L-carnitine, crotonobetaine, {gamma}-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or {gamma}-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl-{sup 14}C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl-{sup 14}C]crotonobetaine (yield about 50 %), [methyl-{sup 14}C]glycine betaine and [methyl-{sup 14}C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author).

  8. Dietary L-Carnitine and energy and lipid metabolism in African catfish (Clarias gariepinus) juveniles

    NARCIS (Netherlands)

    A. Ozório, de R.O.

    2001-01-01

    As the lipid content of the diet increases so does the requirement for certain components involved in lipid metabolism. Carnitine is a normal constituent of animal tissues and plasma, which is required for the transport of long-chain fatty acids (LCFAs) to the site of

  9. Effects of vitamin C and L-carnitine supplementation on metabolic ...

    African Journals Online (AJOL)

    Background: Fasting as a means of protest or religious purposes have increased in the last two decades, individuals involved take only water and supplements. This study investigated the roles of vitamin C and L-carnitine on metabolic parameters during fasting and re-feeding. Methods: Sixty male Sprague-Dawley rats ...

  10. Proximate Composition, and -Carnitine and Betaine Contents in Meat from Korean Indigenous Chicken

    Directory of Open Access Journals (Sweden)

    Samooel Jung

    2015-12-01

    Full Text Available This study investigated the proximate composition and l-carnitine and betaine content of meats from 5 lines of Korean indigenous chicken (KIC for developing highly nutritious meat breeds with health benefits from the bioactive compounds such as l-carnitine and betaine in meat. In addition, the relevance of gender (male and female and meat type (breast and thigh meat was examined. A total of 595 F1 progeny (black [B], grey-brown [G], red-brown [R], white [W], and yellow-brown [Y] from 70 full-sib families were used. The moisture, protein, fat, and ash contents of the meats were significantly affected by line, gender, and meat type (p<0.05. The males in line G and females in line B showed the highest protein and the lowest fat content of the meats. l-carnitine and betaine content showed effects of meat type, line, and gender (p<0.05. The highest l-carnitine content was found in breast and thigh meats from line Y in both genders. The breast meat from line G and the thigh meat from line R had the highest betaine content in males. The female breast and thigh meats showed the highest betaine content in line R. These data could be valuable for establishing selection strategies for developing highly nutritious chicken meat breeds in Korea.

  11. Effects of L-carnitine supplementation into diets with two different fat ...

    African Journals Online (AJOL)

    sevilay

    or without supplemental L-carnitine (0 or 50 mg/kg diet) on growth ... The cold carcass yield of quails fed the diet containing .... Temperature was kept at ...... crude fat content in breast muscle of male broilers increased significantly upon the ...

  12. Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency

    DEFF Research Database (Denmark)

    Olpin, S E; Afifi, A; Clark, S

    2003-01-01

    Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients...

  13. Effects of ICRF-187 and L-Carnitine on bleomycin-induced lung toxicity in rats

    International Nuclear Information System (INIS)

    Shouman, Samia A.; Abdel-Hamid, M.A.; Hassan, Zeinab A.; Mansour, Heba H.

    2002-01-01

    The possible modulatory effects of ICRF-187 and L-carnitine against bleomycin-induced pulmonary toxicity in male rats were investigated. Repeated administration of bleomycin (10 mg/kg, twice weekly for 6 consecutive weeks) produced significant lung toxicity. The toxicity was manifested by significant increase in normal contents of lipid peroxide (LPO, 91.7%) reduced glutathione (GSH, 73.2%) and oxidized glutathione (GSSG, 135.4%) as well as the activity of superoxide dismutase (SOD, 222.7%). Thirty minutes prior to bleomycin treatment, other groups of rats received either ICRF-187 (95 mg/kg) or L-carnitine (500 mg/kg) adopting the same schedule of treatment as in bleomycin-treated group. L-carnitine decreased bleomycin-induced elevations in SOD activity, GSH and GSSG contents, however, it failed to suppress the increase in LPO level. On the other hand, treatment with ICRF-187 returned back all the elevated biochemical parameters induced by bleomycin to nearly normal levels. In conclusion, the results of this study showed a potential capability of ICRF-187 to mitigate the bleomycin-induced lung injury. Moreover, despite the inability of L-carnitine to change the elevated LPO content, it was able however, to decrease the elevated endogenous antioxidant parameters. (author)

  14. Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice

    NARCIS (Netherlands)

    Spiekerkoetter, Ute; Tokunaga, Chonan; Wendel, Udo; Mayatepek, Ertan; Ijlst, Lodewijk; Vaz, Frederic M.; van Vlies, Naomi; Overmars, Henk; Duran, Marinus; Wijburg, Frits A.; Wanders, Ronald J.; Strauss, Arnold W.

    2005-01-01

    Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is the most common long-chain fatty acid oxidation defect and presents with heterogeneous clinical manifestations. Accumulation of long-chain acylcarnitines and deficiency of free carnitine have often been proposed to play an important

  15. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

    Directory of Open Access Journals (Sweden)

    Kraft Matthias

    2012-07-01

    Full Text Available Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4% in controls (p  Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

  16. The effect of L-carnitine on carbonic anhydrase level in rats exposed ...

    African Journals Online (AJOL)

    It plays an important regulatory role in the mitochondria and is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids or fats for the generation of metabolic energy. The functions of L-carnitine in skeletal muscle are critical to sustaining normal bioenergetics during exercise ...

  17. L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

    Science.gov (United States)

    St-Onge, Maude; Ajmo, Ian; Poirier, Diane; Laliberté, Martin

    2013-09-01

    The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

  18. Effect of carnitine supplementation on fatigue level in the gastrocnemius muscle of trained and sedentary rats

    Directory of Open Access Journals (Sweden)

    Rossana Anelice Gomez

    2012-04-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2012v14n3p324 L-carnitine, considered to be of great value in metabolic processes, plays an important role in the mitochondrial β-oxidation process. It may be used to improve athletic performance and to maintain a higher workload during exercise. This study aimed to investigate the effect of L-carnitine supplementation on muscle fatigue in sciatic nerve-gastrocnemius muscle preparations in sedentary and trained rats. The animals were divided into 4 groups: non-supplemented sedentary (NSS, supplemented sedentary (SS, non-supplemented trained (NST, and supplemented trained (ST rats. The animals were trained in daily 1-h sessions (5 days/week and received chronic oral L-carnitine supplementation (1 mg/mL for 4 weeks. Muscle fatigue was determined by supramaximal tetanic stimulation of the sciatic nerve (50 Hz. Time values for strength reduction were significantly different (p<0.05 between NSS vs. SS and NST vs. ST rats. No significant differences were observed between SS vs. ST and NST vs. NSS rats. These findings demonstrate that L-carnitine lengthen the time required for induction of muscle fatigue.

  19. L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.

    Science.gov (United States)

    Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F

    2017-05-01

    Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

    Science.gov (United States)

    Stark, Romana; Reichenbach, Alex; Andrews, Zane B

    2015-12-15

    The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

  1. Protective Role of Carnitine against the Harmful Biological Effects of Paracetamol and Radiation Exposure in Male Albino Rats

    International Nuclear Information System (INIS)

    Abd El Rahman, N.A.

    2012-01-01

    L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain fatty acids to produce energy. Furthermore it has been shown to protect cells from per oxidative stress. The objective of the present study was to evaluate the efficacy of L-carnitine on hepatotoxicity and nephrotoxicity induced by paracetamol, γ-radiation, and paracetamol + γ-radiation. Male albino rats were divided into 8 groups. 1-Control group: rats not subject to any treatment, 2-Carnitine group: rats received L-carnitine (0.5 ml/Kg body weight) via intraperitoneal injection during 21 days, 3-Paracetamol group: rats received paracetamol (50 mg/kg body) via intraperi-toneal injection during 21 days, 4- Carnitine + Paracetamol group: rats received L-carnitine in parallel to paracetamol treatment, 5- Radiation groups: rats were whole body gamma irradiated with 7 Gy, 6- Carnitine + Radiation group: rats received L-carnitine for 21 days before whole body gamma irradiation with 7Gy, 7- Paracetamol + Radiation group: rats received paracetamol during 21 days before whole body gamma irradiation, 8- Carnitine + Paracetamol + Radiation group: rats received L-carnitine parallel to paracetamol during 21 days before whole body gamma irradiation.The results demonstrated that rats receiving paracetamol, as well as whole body gamma irradiated rats and rats receiving paracetamol and irradiated showed a significant increase of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) activities, and a significant decrease of gamma-glutamyl transpeptidase (GGT) activity indicating liver injury. A significant increase of urea, creatinine and uric acid levels was recorded also indicating kidney damage. Alteration in liver and kidney functions was accompanied by a significant increase in the content of thiobarbituric acid reactive substances (TBARS) associated with a significant decrease in glutathione (GSH) content and superoxide

  2. Acetyl L-Carnitine Modulating Irradiation Induced Cardio-Pulmonary Toxicity in Rats

    International Nuclear Information System (INIS)

    Gharib, O.A.

    2006-01-01

    In The Present study male adult Wister albino rats were irradiated at 4 Gy whole body gamma irradiation and Acetyl L-carnitine (ALC) was evaluated as a potential radio-protector under conditions that would model the oxidative stress syndrome. ALC protect the heart and lung from the depletion of SOD, GSHPx activities and GSH content followed radiation exposure. Protection from the increase of malonaldehyde (MDA) in heart and lung tissues as well as serum creatine phosphokinase (CPK), AST and LDH has been observed. These results imply that ALC can act as a radio-protector against many aspects of oxidative damage. ALC is an ester of the tri methylated amino acid L-carnitine, and is synthesized endogenously in the human brain, liver and kidney by the enzyme ALC transferase or obtained from dietary sources (Goa and Brogden, 1987). L carnitine and short chain derivatives are essential cofactors for mitochondrial transport and oxidation of long chain fatty acid and act also as scavengers of oxygen free radicals in mammalian tissue (Izgut-Uysal et al., 2001). The transport of ALC and PLC occurs more easily than L-carnitine through the lipid component of the intestinal barrier suggesting possible better oral bioavailability of the esters than L-carnitine (Marciniani et al., 1991). ALC has antioxidant activity towards oxidative stress via an inhibition of the increase in lipid hydro peroxidation (Yasui et al., 2002). ALC significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma (Marciniani et al., 1991) and has also shown neuro-protective effect in rats (Bigini et al., 2002)

  3. Serum levo-carnitine levels and skeletal muscle functions in type 2 diabetes mellitus in rodents

    International Nuclear Information System (INIS)

    Aleem, S.B.; Hussain, M.M.; Farooq, Y.

    2013-01-01

    Objective: To study serum levo-carnitine (l-carnitine) levels and isometric contraction, force frequency relationship and fatigue of rodent skeletal muscles in type 2 diabetes mellitus. Study Design: Randomized controlled trial. Place and Duration of Study: Physiology Department, Army Medical College, Rawalpindi, from January 2009 to January 2010. Methodology: Sixty Sprague-Dawley rats were randomly divided into two groups; group I (control), fed on normal diet ad libitum and Group II (diabetic), fed on high fat diet and administered streptozocin to induce type 2 diabetes mellitus (T2DM). At 21st day, plasma glucose and TG/HDL ratio were measured to confirm the development of T2DM in group II. At 28th day, blood was drawn by intracardiac puncture to estimate serum levo-carnitine levels. Contractile functions of skeletal muscles were assessed by using iWorx AHK/214 physiological data acquisition unit. Simple muscle twitches, maximum isometric twitch tension (MITT), time-to-peak twitch tension (TPTT) and time-to-relax to 50% of the peak twitch tension (1/2RT) of extensor digitorum muscles were recorded. Muscles were stimulated at higher frequencies to determine maximum fused tetanic tension (MFTT), maximum fused tetanic tension after fatigue protocol (TTFP) and recovery from fatigue (RF). Results: Serum levo-carnitine level decreased significantly in the diabetic group. Both groups had similar MITT, TPTT and 1/2RT but decline in MFTT, TTFP and RF was significant in the diabetic rats. Conclusion: T2DM adversely affected serum levo-carnitine levels and the contractile functions of rodent skeletal muscle at high frequency stimulation. (author)

  4. Radiolysis of D(+)-carnitine by 60Co-γ-radiation and formation of L(+)-β-methylcholine

    International Nuclear Information System (INIS)

    Loester, Heinz; Strack, Erich; Seim, Hermann

    1986-01-01

    The radiolysis of D(+)-carnitine by 60 Co-γ-radiation was examined to obtain optically active β-methylcholine. It was found that the radiolysis leads to a number of trimethylammonium bases but to no other betaines. (+)-β-Methylcholine and acetonyltrimethylammonium could be identified by means of common analytical methods. The amounts of methylamines formed by irradiation were very small. Racemization of the D(+)-carnitine did not occur during irradiation, L(-)-carnitine was not found when an enzymatical determination method was used. The fact that (+)-β-methylcholine was formed from D(+)-carnitine is pharmacologically important, because acetyl-L(+)-β-methylcholine has a strong interaction with muscarinic receptors. (author)

  5. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    OpenAIRE

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-01-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in...

  6. The effect of fermented buckwheat on producing l-carnitine- and γ-aminobutyric acid (GABA)-enriched designer eggs.

    Science.gov (United States)

    Park, Namhyeon; Lee, Tae-Kyung; Nguyen, Thi Thanh Hanh; An, Eun-Bae; Kim, Nahyun M; You, Young-Hyun; Park, Tae-Sub; Kim, Doman

    2017-07-01

    The potential of fermented buckwheat as a feed additive was studied to increase l-carnitine and γ-aminobutyric acid (GABA) in designer eggs. Buckwheat contains high levels of lysine, methionine and glutamate, which are precursors for the synthesis of l-carnitine and GABA. Rhizopus oligosporus was used for the fermentation of buckwheat to produce l-carnitine and GABA that exert positive effects such as enhanced metabolism, antioxidant activities, immunity and blood pressure control. A novel analytical method for simultaneously detecting l-carnitine and GABA was developed using liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS. The fermented buckwheat extract contained 4 and 34 times more l-carnitine and GABA respectively compared with normal buckwheat. Compared with the control, the fermented buckwheat extract-fed group showed enriched l-carnitine (13.6%) and GABA (8.4%) in the yolk, though only l-carnitine was significantly different (P < 0.05). Egg production (9.4%), albumen weight (2.1%) and shell weight (5.8%) were significantly increased (P < 0.05). There was no significant difference in yolk weight, and total cholesterol (1.9%) and triglyceride (4.9%) in the yolk were lowered (P < 0.05). Fermented buckwheat as a feed additive has the potential to produce l-carnitine- and GABA-enriched designer eggs with enhanced nutrition and homeostasis. These designer eggs pose significant potential to be utilized in superfood production and supplement industries. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  7. Mild synthesis of [N-methyl-{sup 11}C]-isovaleroyl-(L)-carnitine. The usefulness of a tritium approach

    Energy Technology Data Exchange (ETDEWEB)

    Angelini, G.; Carnevaletti, F.; Margonelli, A.; Corsi, G. [Istituto di Chimica Nucleare - C.N.R., C.P. 10, Rome (Italy); Ragni, P. [Istituto di Chimica Nucleare -- C.N.R., C.P. 10 -- 00016 Monterotondo Stazione, Roma, (Italy); Fazio, F.; Todde, S. [Istituto di Neuroscienze e Bioimmagini - C.N.R., H.S. Raffaele, Milan (Italy); Tinti, O. [Sigma-Tau, Industrie Farmaceutiche Riunite S.p.A., Pomezia, Rome (Italy)

    1999-02-01

    The title carnitine derivative was labelled both with [{sup 11}C]methyl iodide and [{sup 3}H]methyl iodide. The former was synthesized in order to improve the knowledge of the acyl carnitines fate in humans. The latter was synthesized, at approximately the same concentration level as that of the former, in order to optimize its radiosynthesis, taking advantage from the long half-life of the tritium.

  8. Mild synthesis of [N-methyl-11C]-isovaleroyl-(L)-carnitine. The usefulness of a tritium approach

    International Nuclear Information System (INIS)

    Angelini, G.; Carnevaletti, F.; Margonelli, A.; Corsi, G.; Ragni, P.; Fazio, F.; Todde, S.; Tinti, O.

    1999-01-01

    The title carnitine derivative was labelled both with [ 11 C]methyl iodide and [ 3 H]methyl iodide. The former was synthesized in order to improve the knowledge of the acyl carnitines fate in humans. The latter was synthesized, at approximately the same concentration level as that of the former, in order to optimize its radiosynthesis, taking advantage from the long half-life of the tritium

  9. L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

    Directory of Open Access Journals (Sweden)

    Hisashi Ishikawa

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC. Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid, an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1 high-fat diet (HFD (control group; 2 HFD mixed with 0.28% L-carnitine (L-carnitine group; and 3 HFD mixed with 0.01% α-tocopherol (α-tocopherol group. After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by

  10. Marked elevation in plasma trimethylamine-N-oxide (TMAO in patients with mitochondrial disorders treated with oral l-carnitine

    Directory of Open Access Journals (Sweden)

    H.D. Vallance

    2018-06-01

    Full Text Available Oral supplementation with l-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of l-carnitine, trimethylamine oxide (TMAO, is an independent and dose-dependent risk factor for cardiovascular disease (CVD. Given the limited data demonstrating efficacy with oral l-carnitine therapy and the newly raised questions of potential harm, we assessed plasma TMAO levels in patients with mitochondrial disease with and without oral l-carnitine supplementation. Nine subjects were recruited and completed the study. Eight out of 9 subjects at baseline had plasma TMAO concentrations <97.5th percentile (<15.5 μM. One subject with stage 3 renal disease, had marked elevation in plasma TMAO (pre 33.98 μm versus post 101.6 μm. Following at least 3 months of l-carnitine supplementation (1000 mg per day, plasma TMAO levels were markedly increased in 7out of 9 subjects; overall, plasma TMAO significantly increased 11.8-fold (p < 0.001 from a baseline median level of 3.54 μm (interquartile range (IQR 2.55–8.72 to 43.26 (IQR 23.99–56.04 post supplementation. The results of this study demonstrate that chronic oral l-carnitine supplementation markedly increases plasma TMAO levels in subjects with mitochondrial disorders. Further studies to evaluate both the efficacy and long term safety of oral l-carnitine supplementation for the treatment of mitochondrial disorders are warranted. Keywords: l-carnitine, Trimethylamine N-oxide, Mitochondrial disorders

  11. Propionyl-l-carnitine: Labelling in the N-methyl position with Carbon-11 and pharmacokinetic studies in rats

    International Nuclear Information System (INIS)

    Davenport, Raymond J.; Law, Marilyn P.; Pike, Victor W.; Osman, Safiye; Poole, Keith G.

    1995-01-01

    The prospective therapeutic, propionyl-l-carnitine, was labelled in the N-methyl position with the positron-emitter, carbon-11 (t (1(2)) = 20.4 min), with a view to studying its pharmacokinetics in humans using PET. Labelling was achieved by methylating nor-propionyl-l-carnitine hydrochloride with no-carrier-added [ 11 C]iodomethane (produced from cyclotron-produced [ 11 C]carbon dioxide) in ethanol in the presence of 1,2,2,6,6,-pentamethylpiperidine. HPLC of the reaction mixture on a strong cation exchange column provided high purity [N-methyl- 11 C]propionyl-l-carnitine in 62% radiochemical yield (decay-corrected from [ 11 C]iodomethane), ready for intravenous administration within 35 min from the end of radionuclide production. [N-methyl- 11 C]Propionyl-l-carnitine, given intravenously to rats, cleared rapidly from plasma. A slow uptake of radioactivity into myocardium and striated muscle was observed. In plasma, unchanged tracer represented 84% of the radioactivity at 2.5 min and 2.5% of the radioactivity at 60 min. In heart, unchanged tracer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity detected in plasma and heart was identified as [N-methyl- 11 C]l-carnitine and [N-methyl- 11 C]acetyl-l-carnitine

  12. Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats.

    Science.gov (United States)

    Amin, Kamal A; Nagy, Mohamed A

    2009-10-16

    Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments) for 4 weeks.Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR

  13. Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

    Directory of Open Access Journals (Sweden)

    Amin Kamal A

    2009-10-01

    Full Text Available Abstract Background Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. Aim To investigate the development of obesity in response to a high fat diet (HFD and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. Method White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr, 30 rats fed a high-fat diet (HFD for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD, the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments for 4 weeks. Body weight, lipid profile & renal function (urea, uric acid creatinine ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB the oxidative stress marker reduced glutathione (GSH, and Malondialdehyde (MDA catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Results Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG, total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile. Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia

  14. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats.

    Science.gov (United States)

    Ando, S; Tadenuma, T; Tanaka, Y; Fukui, F; Kobayashi, S; Ohashi, Y; Kawabata, T

    2001-10-15

    The effects of a carnitine derivative, acetyl-L-carnitine (ALCAR), on the cognitive and cholinergic activities of aging rats were examined. Rats were given ALCAR (100 mg/kg) per os for 3 months and were subjected to the Hebb-Williams tasks and a new maze task, AKON-1, to assess their learning capacity. The learning capacity of the ALCAR-treated group was superior to that of the control. Cholinergic activities were determined with synaptosomes isolated from the cortices. The high-affinity choline uptake by synaptosomes, acetylcholine synthesis in synaptosomes, and acetylcholine release from synaptosomes on membrane depolarization were all enhanced in the ALCAR group. This study indicates that chronic administration of ALCAR increases cholinergic synaptic transmission and consequently enhances learning capacity as a cognitive function in aging rats. Copyright 2001 Wiley-Liss, Inc.

  15. The effects of acute L-carnitine administration on ventilatory breakpoint and exercise performanceduring incremental exercise

    OpenAIRE

    Mojtaba Kaviani; Maryam Nourshahi; Farhad Shokoohi

    2009-01-01

    (Received 31 October, 2009 ; Accepted 10 March, 2010)AbstractBackground and purpose: Many athletes adopt nutritional manipulations to improve their performance. Among the substances generally consumed is carnitine (L-trimethyl-3-hydroxy-ammoniobutanoate) which has been used by athletes as an ergogenic aid, due to its role in the transport of long-chain fatty acids across mitochondrial membranes. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widel...

  16. Effect of telmisartan in combined with L-carnitine on peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Effect of telmisartan in combined with L-carnitine on peritoneal dialysis patients

    2016-07-01

    Full Text Available Objective: To observe the therapeutic effect of telmisartan in combined with L-carnitine on the peritoneal dialysis (PD patients in order to guide the clinical medication. Methods: A total of 80 patients with chronic renal failure (CRF who were admitted in our hospital from November, 2011 to January, 2014 for PD were included in the study and randomized into the treatment group and the control group. The patients in the two groups were routinely performed with PD. The patients in the treatment group were given L-carnitine oral liquid, 10mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were given L-carnitine oral liquid, 10mL/time, 3 times a day. The patients in the two groups were treated for 24 weeks continuously. The serum SCr and BUN levels before and after treatment in the two groups were observed. RRF was calculated. The changes of daily average urine volume and blood pressure before and after treatment in the two groups were observed. Results: After treatment, the reduced degree of SCr and BUN in the treatment group was significantly greater than that in the control group, while the reduced degree of RRF was significantly less than that in the control group (P<0.05. After treatment, the daily urine volume was reduced, but the reduced degree in the treatment group was significantly less than that in the control group (P<0.05. After treatment, SBP and DBP were reduced, but the reduced degree in the treatment group was significantly superior to that in the control group (P<0.05. Conclusions: Telmisartan in combined with L-carnitine applied in PD patients can effectively delay the loss of RRF and the reduction of urine volume, and regulate the blood pressure in order to alleviate the clinical symptoms and improve the patients’ living qualities.

  17. Carnitine pretreatment can partially change the excitability of the immature nervous tissue

    Czech Academy of Sciences Publication Activity Database

    Marešová, D.; Rauchová, Hana; Jandová, K.; Valkounová, I.; Koudelová, J.; Trojan, S.

    2001-01-01

    Roč. 50, č. 4 (2001), s. 439-442 ISSN 0862-8408 R&D Projects: GA ČR GA303/98/0473; GA ČR GA305/99/0976; GA MŠk LN00A069 Grant - others:GA UK(CZ) 241/1998 Institutional research plan: CEZ:AV0Z5011922 Keywords : carnitine treatment * epileptic seizures * hypobaric hypoxia Subject RIV: FH - Neurology Impact factor: 1.027, year: 2001

  18. Hypoxia-induced lipid peroxidation in rat brain and protective effect of carnitine and phosphocreatine

    Czech Academy of Sciences Publication Activity Database

    Rauchová, Hana; Koudelová, J.; Drahota, Zdeněk; Mourek, J.

    2002-01-01

    Roč. 27, č. 9 (2002), s. 899-904 ISSN 0364-3190 R&D Projects: GA MŠk LN00A069 Grant - others:GA UK(XC) 22/2001 Institutional research plan: CEZ:AV0Z5011922 Keywords : hypobaric hypoxia-lipid peroxidation * carnitine * lactate/pyruvate ratio Subject RIV: ED - Physiology Impact factor: 1.672, year: 2002

  19. Inhibition of Palmityl Carnitine Oxidation in Rat Liver Mitochondria by Tert-Butyl Hydroperoxide

    Czech Academy of Sciences Publication Activity Database

    Červinková, Z.; Rauchová, Hana; Křiváková, P.; Drahota, Zdeněk

    2008-01-01

    Roč. 57, č. 1 (2008), s. 133-136 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GD303/03/H065; GA ČR(CZ) GA305/04/0500; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50110509 Keywords : liver mitochondria * palmityl carnitine oxidation * tert-butylhydroperoxide Subject RIV: ED - Physiology Impact factor: 1.653, year: 2008

  20. effect of dl-carnitine on tissue content of ad eno ine triphospha te

    African Journals Online (AJOL)

    BSN

    values of 16.2 ± 5.2µ mols lg dry weight for ATP and I 1.7± 2.5 ~11nols/g dry weight for CP in normal (non ischaem1c) myocardial tissue. Continuous perfusion of the heans "ith perfusate contaming 4.9µmols/ml. DL-Carnitine appeared to prevent the lowermg of ATP and CP levels as a result of induction of ischaemia.

  1. Biosynthesis of the Essential Fatty Acid Oxidation Cofactor Carnitine Is Stimulated in Heart and Liver after a Single Bout of Exercise in Mice

    Directory of Open Access Journals (Sweden)

    Tom L. Broderick

    2018-01-01

    Full Text Available We determined whether one single bout of exercise stimulates carnitine biosynthesis and carnitine uptake in liver and heart. Free carnitine (FC in plasma was assayed using acetyltransferase and [14C]acetyl-CoA in Swiss Webster mice after 1 hour of moderate-intensity treadmill running or 4 hours and 8 hours into recovery. Liver and heart were removed under the same conditions for measurement of carnitine biosynthesis enzymes (liver butyrobetaine hydroxylase, γ-BBH; heart trimethyllysine dioxygenase, TMLD, organic cation transporter-2 (OCTN2, carnitine transporter, and liver peroxisome proliferator-activated receptor-alpha (PPARα, transcription factor for γ-BBH and OCTN2 synthesis. In exercised mice, FC levels in plasma decreased while heart and liver OCTN2 protein expressed increased, reflecting active uptake of FC. During recovery, the rise in FC to control levels was associated with increased liver γ-BBH expression. Protein expression of PPARα was stimulated in liver after exercise and during recovery. Interestingly, heart TMLD protein was also detected after exercise. Acute exercise stimulates carnitine uptake in liver and heart. The rapid return of FC levels in plasma after exercise indicates carnitine biosynthesis by liver is stimulated to establish carnitine homeostasis. Our results suggest that exercise may benefit patients with carnitine deficiency syndromes.

  2. Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report.

    Science.gov (United States)

    Isse, Naohi; Miura, Yoh; Obata, Toshiyuki; Takahara, Noriko

    2013-12-30

    L-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia. A 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient's ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily). This case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient's serum ammonium levels.

  3. In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    Background: A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography–tandem mass spectrometry. Results: Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased

  4. Role of carnitine in ameliorating the lead and / or irradiation induced toxicity in male albino rats

    International Nuclear Information System (INIS)

    El-Sayed, N.M.

    2005-01-01

    This work: aimed to investigate the protective effect of carnitine (3-hydroxy-4-N-trimethyl amino butyric acid) on the contents of total protein, albumin, glucose and lipid peroxides as malonaldehyde (MDA) in serum, in addition to liver glycogen and lipid peroxides content 1, 2, 4 weeks after exposure of rats to a collective dose of 4 Gy whole body gamma irradiation and / or lead treatment. Adult male rats received lead (50 mg/kg body weight) and / or exposed to fractionated dose (4 Gy) of gamma irradiation delivered as 0.5 Gy twice weekly for four weeks. Results of the present study revealed that fractionated whole body gamma irradiation and / or lead administration induced cellular damage manifested by a significant decrease in serum total protein and albumin, and a significant increase in serum glucose and MDA content as well as significant increase in liver glycogen and MDA. Administration of carnitine (200 mg/kg b.wt.) before lead and / or gamma irradiation, has significantly ameliorated the observed changes, indicating the prophylactic action of carnitine on lead and / or irradiation toxicity

  5. The effects of L-carnitin in Budd-Chiari syndrome in a domestic cat

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    Aliye Sağkan Öztürk

    2016-03-01

    Full Text Available This paper describes a thrombosis in the vena cava caudalis of a 15 year-old cat with ascites. Trauma and eventually feline enteric corona virus infection in the cat were not detected. In the intrahepatic region, a blockage of vena cava caudalis was brought to light by ultrasonographic imaging. An aspirate of abdominal fl uid revealed modified transudate. Liver enzyme levels were increased in the serum sample of the cat. The levels of total oxidant status (TOS and total antioxidant status (TAS were elevated in the peritoneal fluid. Liver protection diet with L-carnitine, diuretic therapy and antimicrobial drugs were administrated for treatment of the cat. During the continuous treatment, the amount of abdominal fluid decreased, but never completely absorbed. L-carnitine was administered to the cat during the time of treatment, and subsequently the levels of liver enzymes decreased. However, the cat died because of recurrent ascites and persistent thrombosis. In conclusion, ultrasonographic examination was very reliable, non-invasive and highly useful diagnostic method for BCS and L-carnitine has crucial effects on the quality of life, energy metabolism and liver enzyme levels. However, the blockage of the vena cava caudalis could not completely respond to medical treatment and thrombosis should be eliminated by surgical intervention.

  6. Orlistat interaction with sibutramine and carnitine. A physicochemical and theoretical study

    Science.gov (United States)

    Nicolás-Vázquez, Inés; Hinojosa Torres, Jaime; Cruz Borbolla, Julián; Miranda Ruvalcaba, René; Aceves-Hernández, Juan Manuel

    2014-03-01

    Chemical degradation of orlistat, (ORT) after melting and reaction of decomposition byproducts with sibutramine, SIB was studied. Interactions between the active pharmaceutical ingredients by using thermal analysis, TA, methods and other experimental techniques such as PXRD, IR and UV-vis spectroscopies were carried out to investigate chemical reactions between components. It was found that orlistat melts with decomposition and byproducts quickly affect sibutramine molecule and then reacting also with carnitine, CRN when the three active pharmaceutical ingredients (API's) are mixed. However ORT byproducts do not react when ORT is mixed only with carnitine. It was found that compounds containing chlorine atoms react easily with orlistat when the temperature increases up to its melting point. Some reaction mechanisms of orlistat decomposition are proposed, the fragments in the mechanisms were found in the corresponding mass spectra. Results obtained indicate that special studies should be carried out in the formulation stage before the final composition of a poly-pill could be established. Similar results are commonly found for compounds very prone to react in presence of water, light and/or temperature. In order to explain the reactivity of orlistat with sibutramine and carnitine, theoretical calculations were carried out and the results are in agreement with the experimental results.

  7. Where does N(ε-trimethyllysine for the carnitine biosynthesis in mammals come from?

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    Luigi Servillo

    Full Text Available N(ε-trimethyllysine (TML is a non-protein amino acid which takes part in the biosynthesis of carnitine. In mammals, the breakdown of endogenous proteins containing TML residues is recognized as starting point for the carnitine biosynthesis. Here, we document that one of the main sources of TML could be the vegetables which represent an important part of daily alimentation for most mammals. A HPLC-ESI-MS/MS method, which we previously developed for the analysis of N(G-methylarginines, was utilized to quantitate TML in numerous vegetables. We report that TML, believed to be rather rare in plants as free amino acid, is, instead, ubiquitous in them and at not negligible levels. The occurrence of TML has been also confirmed in some vegetables by a HPLC method with fluorescence detection. Our results establish that TML can be introduced as free amino acid in conspicuous amounts from vegetables. The current opinion is that mammals utilize the breakdown of their endogenous proteins containing TML residues as starting point for carnitine biosynthesis. However, our finding raises the question of whether a tortuous and energy expensive route as the one of TML formation from the breakdown of endogenous proteins is really preferred when the substance is so easily available in vegetable foods. On the basis of this result, it must be taken into account that in mammals TML might be mainly introduced by diet. However, when the alimentary intake becomes insufficient, as during starvation, it might be supplied by endogenous protein breakdown.

  8. Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle

    International Nuclear Information System (INIS)

    Cederblad, G.; Carlin, J.I.; Constantin-Teodosiu, D.; Harper, P.; Hultman, E.

    1990-01-01

    Radioisotopic assays for the determination of acetyl-CoA, CoASH, and acetylcarnitine have been modified for application to the amount of human muscle tissue that can be obtained by needle biopsy. In the last step common to all three methods, acetyl-CoA is condensed with [14C]oxaloacetate by citrate synthase to give [14C]-citrate. For determination of CoASH, CoASH is reacted with acetylphosphate in a reaction catalyzed by phosphotransacetylase to yield acetyl-CoA. In the assay for acetylcarnitine, acetylcarnitine is reacted with CoASH in a reaction catalyzed by carnitine acetyltransferase to form acetyl-CoA. Inclusion of new simple steps in the acetylcarnitine assay and conditions affecting the reliability of all three methods are also described. Acetylcarnitine and free carnitine levels in human rectus abdominis muscle were 3.0 +/- 1.5 (SD) and 13.5 +/- 4.0 mumol/g dry wt, respectively. Values for acetyl-CoA and CoASH were about 500-fold lower, 6.7 +/- 1.8 and 21 +/- 8.9 nmol/g dry wt, respectively. A strong correlation between acetylcarnitine (y) and short-chain acylcarnitine (x), determined as the difference between total and free carnitine, was found in biopsies from the vastus lateralis muscle obtained during intense muscular effort, y = 1.0x + 0.5; r = 0.976

  9. Musculus soleus of rats at physical activity and L-carnitine and creatine phosphate effect

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    Irina A. Khutorskaya

    2017-09-01

    Full Text Available Introduction: The study of the effect of metabolic drugs on the histochemical characteristics of soleus muscle is relevant for solving the problem of providing the training process in Russia with non-doping drugs for safe correction of the consequences of intense physical activity in athletes. Materials and Methods: Dynamic physical activity in rats (n = 24 was simulated by swimming “to the limit” with weighting of 10 % of body weight (20 days, 1 time per day. The experimental animals were divided into four groups (6 animals each: № 1 – control, № 2 – swimming + isotonic NaCl solution, № 3 and № 4 – swimming + L-carnitine or creatine phosphate 100.0 mg/kg daily intraperitoneally. The object of the study was musculus soleus. Differentiation of muscle fibers was carried out by the intensity of histochemical activity of succinate dehydrogenase (SDG and alkaline stable adenosine triphosphate (ATP of myosin. The percentage of muscle fibers was evaluated and their diameter was defined by the direct morphometry. The obtained data were treated statistically by Student’s T-test. Results: Swimming of the animals “to the limit” do not affect the ratio of fibers with different phenotypes in the soleus muscle. This indicator is genetically determined and was not modified by L-carnitine and creatine phosphate. Dynamic physical activity promotes the development of hypertrophy of muscle fibers of various types. The investigated medicaments of the metabolic type either do not influence on the formation of exerciseinduced hypertrophy (predominantly creatine phosphate or reduce the intensity of the hypertrophic process (predominantly L-carnitine under dynamic physical activity. Discussion and Conclusions: The obtained data indicate L-carnitine and creatine phosphate do not have an anabolic effect. Taking into account the relevant data on ability of L-carnitine and creatine phosphate to effectively correct a negative effects of intensive

  10. Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

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    Li Jin-Lian

    2012-03-01

    Full Text Available Abstract Background Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H2O2-induced cytotoxicity in a normal human hepatocyte cell line, HL7702. Methods We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS levels, activities and protein expressions of superoxide dismutase (SOD and catalase (CAT, and malondialdehyde (MDA formation. Expressions of peroxisome proliferator-activated receptor (PPAR-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test. Results The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1 and acyl-CoA oxidase (ACOX induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886. Conclusions Taken together, our findings suggest that L-carnitine could protect HL

  11. Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.

    Science.gov (United States)

    Videen, J S; Haseler, L J; Karpinski, N C; Terkeltaub, R A

    1999-08-01

    The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.

  12. Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture

    International Nuclear Information System (INIS)

    Pillich, Rudolf Tito; Scarsella, Gianfranco; Risuleo, Gianfranco

    2005-01-01

    It is shown in literature that stress, such as deprivation of trophic factors and hypoxia, induces apoptosis in cultured cells and in tissues. In light of these results, we explored the possibility of protecting cells from programmed death by improving the metabolism of the mitochondrion. To this end, acetyl-L-carnitine was administered at various concentrations under conditions of serum deprivation. The choice of this drug was based on the accepted notion that acetyl-L-carnitine is able to stabilize mitochondrial membranes and to increase the supply of energy to the organelle. The results presented here indicate that the drug protects cells from apoptotic death: this is demonstrated by a lower positivity to the TUNEL reaction and by a strong reduction of the apoptotic DNA ladder in serum-deprived cells. The involvement of the mitochondrial apoptotic pathway was assessed by cytochrome C release and immunoreactivity to caspase 3. Moreover, acetyl-L-carnitine stimulates cell proliferation

  13. Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

    2013-01-01

    Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

  14. Co-ordinate induction of hepatic mitochondrial and peroxisomal carnitine acyltransferase synthesis by diet and drugs.

    Science.gov (United States)

    Brady, P S; Marine, K A; Brady, L J; Ramsay, R R

    1989-01-01

    The present studies examined the effect of agents that induce peroxisomal and mitochondrial beta-oxidation on hepatic mitochondrial carnitine palmitoyltransferase (CPT) and peroxisomal carnitine acyltransferase [CPTs of Ramsay (1988) Biochem. J. 249, 239-245; COT of Farrell & Bieber (1983) Arch. Biochem. Biophys. 222, 123-132 and Miyazawa, Ozasa, Osumi & Hashimoto (1983) J. Biochem. 94, 529-542]. In the first studies, high fat diets containing corn oil or fish oil were used to induce peroxisomal and mitochondrial enzymes. Rats were fed one of three diets for 4 weeks: (1) low fat, with corn oil as 11% of energy (kJ); (2) high fat, with corn oil as 45% of kJ; (3) high fat, with fish oil as 45% of kJ. At the end of 4 weeks, both mitochondrial CPT and peroxisomal CPTs exhibited increases in activity, immunoreactive protein, mRNA levels and transcription rates in livers of rats fed either high-fat diet compared to the low fat diet. Riboflavin deficiency or starvation for 48 h also increased the peroxisomal CPTs mRNA. A second set of studies used the plasticizer 2-(diethylhexyl)phthalate (DEHP), 0.5% clofibrate or 1% acetylsalicylic acid (fed for 3 weeks) to alter peroxisomal and mitochondrial fatty acid oxidation. With DEHP, the mitochondrial CPT and peroxisomal CPTs activity, immunoreactive protein, mRNA levels and and transcription rate were all increased by 3-5-fold. The peroxisomal CPTs activity, immunoreactive protein, mRNA levels and transcription rate were increased 2-3-fold by clofibrate and acetylsalicylic acid, again similar to mitochondrial CPT. The results of the combined studies using both diet and drugs to cause enzyme induction suggest that the synthesis of the carnitine acyltransferases (mitochondrial CPT and peroxisomal CPTs) may be co-ordinated with each other; however, the co-ordinate regulatory factors have not yet been identified. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:2775196

  15. l-carnitine as a Potential Additive in Blood Storage Solutions: A Study on Erythrocytes

    OpenAIRE

    Soumya, R.; Carl, H.; Vani, R.

    2015-01-01

    Erythrocytes undergo various changes during storage (storage lesion) that in turn reduces their functioning and survival. Oxidative stress plays a major role in the storage lesion and antioxidants can be used to combat this stress. This study elucidates the effects of l-carnitine (LC) on erythrocytes of stored blood. Blood was obtained from male Wistar rats and stored (4 °C) for 20 days in CPDA-1 (citrate phosphate dextrose adenine) solution. Samples were divided into–(i) controls (ii) LC 10 ...

  16. ACETYL-L-CARNITINE AFFECTS THE ELECTRICAL ACTIVITY OF MECHANOSENSORY NEURONS IN HIRUDO MEDICINALIS GANGLIA

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    Giovanna Traina

    2017-04-01

    Full Text Available Was previously discovered that in the leech Hirudo medicinalis, acetyl-l-carnitine (ALC affects forms of non-associative learning, such as sensitization and dishabituation, due to nociceptive stimulation of the dorsal skin in the swim induction behavioural paradigm, likely through modulating the activity of the mechanosensory tactile (T neurons, which initiate swimming. Since was found that ALC impaired sensitization and dishabituation, both of which are mediated by the neurotransmitter serotonin, the present study analyzed how ALC may interfere with the sensitizing response. Was already found that ALC reduced the activity of nociceptive (N neurons, which modulate T cell activity through serotonergic mediation.

  17. [Micronutrients in oncology. Current data about vitamin D, selenium, L-carnitine and vitamin C].

    Science.gov (United States)

    Gröber, Uwe; Mücke, Ralph; Holzhauer, Peter; Kisters, Klaus

    2013-04-01

    Many patients receiving cancer treatment use micronutrient supplements, with the intention to complement their cancer treatment, or help them cope with the therapy- and disease-associated side-effects. Up to 90% of the cancer patients are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants and other micronutrients, such as selenium, L-carnitine and vitamin D are added to conventional cytotoxic therapies. It is imperative that physicians discuss the use ofantioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative, but also potentially beneficial effects.

  18. Influence of L-Carnitine Supplementation on Serum Lipid Profile in Hemodialysis Patients: A Systematic Review and Meta-Analysis

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    Haohai Huang

    2014-02-01

    Full Text Available Background/Aims: An increasing body of evidence demonstrates that L-carnitine plays a pivotal role in lipid metabolism of hemodialysis (HD patients. However, there are still some reservations about its benefits. Therefore, we performed a meta-analysis to assess the effects of L-carnitine supplementation on lipid profile in HD patients. Methods: Literature search was performed to identify the relevant randomized controlled trials that investigated the effects of L-carnitine on the lipid profile of subjects. Two independent authors used an Excel file to extract data and assess trials quality. The primary effect measure was the difference in means of the final lipid measurements between the intervention and control groups. The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. Results: Twelve studies with a total of 391 patients met the inclusion criteria. The use of L-carnitine was not associated with a reduction in the total cholesterol (SMD, -0.11; 95% CI, -0.31 to 0.09, HDL-cholesterol (SMD, 0.01; 95% CI, -0.36 to 0.39, VLDL-cholesterol (SMD, 0.54; 95% CI, -0.06 to 1.14, and the serum triglycerides (SMD, -0.12; 95% CI, -0.36 to 0.12. However, L-carnitine can significantly decrease the LDL-cholesterol (SMD, -0.29; 95% CI, -0.53 to -0.06 in HD patients. In a subgroup meta-analysis, a significant LDL-cholesterol-lowering effect of L-carnitine supplementation was observed in intravenous application group, and patients with longer interventional duration and renal diseases. Conclusion: The limited evidence suggests that there was no effect of L-carnitine on serum total cholesterol, HDL-cholesterol, VLDL-cholesterol and serum triglycerides. By contrast, this meta-analysis suggests a promising effect of L-carnitine on LDL-cholesterol. Further large-scale, well-designed randomized controlled trials are urgently needed

  19. cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase

    International Nuclear Information System (INIS)

    Finocchiaro, G.; Taroni, F.; Martin, A.L.; Colombo, I.; Tarelli, G.T.; DiDonato, S.; Rocchi, M.

    1991-01-01

    The authors have cloned and sequenced a cDNA encoding human liver carnitine palmitoyltransferase an inner mitochondrial membrane enzyme that plays a major role in the fatty acid oxidation pathway. Mixed oligonucleotide primers whose sequences were deduced from one tryptic peptide obtained from purified CPTase were used in a polymerase chain reaction, allowing the amplification of a 0.12-kilobase fragment of human genomic DNA encoding such a peptide. A 60-base-pair (bp) oligonucleotide synthesized on the basis of the sequence from this fragment was used for the screening of a cDNA library from human liver and hybridized to a cDNA insert of 2255 bp. This cDNA contains an open reading frame of 1974 bp that encodes a protein of 658 amino acid residues including 25 residues of an NH 2 -terminal leader peptide. The assignment of this open reading frame to human liver CPTase is confirmed by matches to seven different amino acid sequences of tryptic peptides derived from pure human CPTase and by the 82.2% homology with the amino acid sequence of rat CPTase. The NH 2 -terminal region of CPTase contains a leucine-proline motif that is shared by carnitine acetyl- and octanoyltransferases and by choline acetyltransferase. The gene encoding CPTase was assigned to human chromosome 1, region 1q12-1pter, by hybridization of CPTase cDNA with a DNA panel of 19 human-hanster somatic cell hybrids

  20. Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

    International Nuclear Information System (INIS)

    Ramadan, L.A.

    2003-01-01

    In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicity

  1. L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    An, Jee Hyun; Kim, Yoon Jung; Kim, Kyeong Jin; Kim, Sun Hwa; Kim, Nam Hoon; Kim, Hee Young; Kim, Nan Hee; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Kim, Sin Gon

    2016-10-29

    Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P treatment with L-carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

  2. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    Science.gov (United States)

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-06-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.

  3. Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids

    International Nuclear Information System (INIS)

    Angsten, Gertrud; Valind, Sven; Takalo, Reijo; Neu, Henrik; Meurling, Staffan; Langstroem, Bengt

    2005-01-01

    Methods: Anesthetized pigs were studied with [ 11 C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [ 11 C]-FAs from blood was measured together with the relative distribution of [ 11 C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [ 11 C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [ 11 C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs

  4. Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [{sup 11}C]-labeled fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Angsten, Gertrud [Department of Pediatric Surgery, University Children' s Hospital, S-751 85 Uppsala (Sweden)]. E-mail: gertrud.angsten@surgsci.uu.se; Valind, Sven [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Clinical Physiology, University Hospital, S-751 85 Uppsala (Sweden); Takalo, Reijo [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Clinical Physiology, University Hospital, S-751 85 Uppsala (Sweden); Neu, Henrik [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Organic Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Meurling, Staffan [Department of Pediatric Surgery, University Children' s Hospital, S-751 85 Uppsala (Sweden); Langstroem, Bengt [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Organic Chemistry, Uppsala University, S-751 24 Uppsala (Sweden)

    2005-07-01

    Methods: Anesthetized pigs were studied with [{sup 11}C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [{sup 11}C]-FAs from blood was measured together with the relative distribution of [{sup 11}C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [{sup 11}C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [{sup 11}C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs.

  5. Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening

    DEFF Research Database (Denmark)

    Pedersen, Christina B; Bischoff, Claus; Christensen, Ernst

    2006-01-01

    or compound heterozygous for variations in the IBD gene have been reported. We present IBD deficiency in an additional four newborns with elevated C(4)-carnitine identified by tandem mass spectrometry (MS/MS) screening in Denmark and the United States. Three showed urinary excretions of isobutyryl...

  6. L-carnitine pretreatment protects slow-twitch skeletal muscles in a rat model of ischemia-reperfusion injury.

    Science.gov (United States)

    Demirel, Mert; Kaya, Burak; Cerkez, Cem; Ertunc, Mert; Sara, Yildirim

    2013-10-01

    Ischemia-reperfusion (I/R) injury negatively affects the outcome of surgical interventions for amputated or severely traumatized extremities. This study aimed to evaluate the protective role of l-carnitine on the contractile properties of fast-twitch (extensor digitorum longus [EDL]) and slow-twitch (soleus [SOL]) skeletal muscles following I/R-induced injury in a rat model. Rats were divided into 4 groups (1) saline pretreatment, (2) l-carnitine pretreatment, (3) saline pretreatment and I/R, and (4) l-carnitine pretreatment and I/R. Twitch and tetanic contractions in the EDL and SOL muscles in each group were recorded. Additionally, a fatigue protocol was performed in these muscles. Twitch and tetanic contraction amplitudes were lower in the EDL and SOL muscles in which I/R was induced (P contraction amplitude in the SOL muscles following I/R (P muscles. l-Carnitine pretreatment did not alter the fatigue response in any of the muscles.

  7. Acyl/free carnitine ratio is a risk factor for hepatic steatosis after pancreatoduodenectomy and total pancreatectomy.

    Science.gov (United States)

    Nakamura, Masafumi; Nakata, Kohei; Matsumoto, Hideo; Ohtsuka, Takao; Yoshida, Koji; Tokunaga, Shoji; Hino, Keisuke

    Hepatic steatosis, one of the most frequent long-term complications of pancreatectomy, influences not only hepatic function but also survival rate. However, its risk factors and pathogenesis have not been established. The purpose of this study was to clarify the risk factors for hepatic steatosis after pancreatectomy. In this retrospective study of 21 patients who had undergone pancreatectomy (19 cases of pancreatoduodenectomy and 2 cases of total pancreatectomy), serum carnitine concentrations, fractions of carnitine, and hepatic attenuation on computed tomography images were analyzed with the aim of identifying risk factors for hepatic steatosis. Thirteen (61.9%) of the 21 patients were diagnosed as having hypocarnitinemia after pancreatectomy. Average hepatic attenuation was as low as 42.2HU (±21.3 SD). A high ratio of acyl/free carnitine was associated with less pronounced hepatic attenuation according to both univariate (P pancreatectomy in some patients. The statistical analyses suggest that a high ratio of acyl/free carnitine is an independent risk factor for hepatic steatosis after pancreatectomy. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient

    NARCIS (Netherlands)

    Huizing, M.; Iacobazzi, V.; IJlst, L.; Savelkoul, P.; Ruitenbeek, W.; van den Heuvel, L.; Indiveri, C.; Smeitink, J.; Trijbels, F.; Wanders, R.; Palmieri, F.

    1997-01-01

    The carnitine-acylcarnitine carrier (CAC) catalyzes the translocation of long-chain fatty acids across the inner mitochondrial membrane. We cloned and sequenced the human CAC cDNA, which has an open reading frame of 903 nucleotides. Northern blot studies revealed different expression levels of CAC

  9. Effects of carnitine and its congeners on eicosanoid discharge from rat cells: Implications for release of TNFα

    NARCIS (Netherlands)

    I.M. Garrelds (Ingrid); G.R. Elliott (G.); W.M. Pruimboom (Wanda); F.J. Zijlstra (Freek); I.L. Bonta

    1993-01-01

    textabstractTHE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the

  10. Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

    Science.gov (United States)

    Costa, Rute A P; Fernandes, Mariana P; de Souza-Pinto, Nadja C; Vercesi, Aníbal E

    2013-02-15

    Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury

    Directory of Open Access Journals (Sweden)

    Meryem Akpolat

    2011-03-01

    Full Text Available Objective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6: group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy.

  12. Dietary Carnitine maintains energy reserves and delays fatigue of exercised African catfish (Clarias Gariepinus) fed high fat diets

    NARCIS (Netherlands)

    Ozorio, R.; Ginneken, van V.J.T.; Thillart, van den G.; Verstegen, M.W.A.; Verreth, J.A.J.

    2005-01-01

    Lipids, together with proteins, are traditionally considered as primary fuels during aerobic swimming. The effects of dietary fat and carnitine supplements and exercise on the energy metabolism of juvenile fish were investigated. One hundred African catfish (Clarias gariepinus) were fed four

  13. Effects of acute L-carnitine intake on metabolic and blood lactate levels of elite badminton players.

    Science.gov (United States)

    Eroğlu, Hüseyin; Senel, Omer; Güzel, Nevin A

    2008-04-01

    Purpose of this study is to research the effects of acute L-Carnitine intake on badminton players' metabolic and blood lactate values. A total of 16 Turkish national badminton players (8 male, 8 female) were voluntarily participated into study. MaxVO2, MET, energy consumption, HR (heart rate), VE (minute ventilation), R (respiratory exchange ratio), AT (anaerobic threshold), oxygen pulse and blood lactate (LA) of subjects were measured by Sensormedics VmaxST and Accutrend Lactate Analyzer. The participants were subjected to the test protocol twice before and after 2g of L-Carnitine intake. The data were evaluated by the use of SPSS 13.0 for Windows. No significant differences were found between 1st. (without L-Carnitine intake) and 2nd. (with L-Carnitine intake) measurements of female participants as regards to all measured parameters. There was a significant difference in EMHR (exercise maximum heart rate) of males between two measurements (p0.05). Respiratory exchange ratio of males was significantly different at anaerobic threshold (pbadminton players.

  14. Effects of L-Carnitine Theraphy On Methabolic and Biochemical Changes Caused By Propofol Infusion in Rabbits Undergoing Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Savaş Yılbaş

    2011-08-01

    Full Text Available Objective: Increased lipid mass in the body secondary to long term and high doses of propofol infusion may cause carnitine deficiency. In this study; we aimed to investigate the effects of carnitine, given for treatment purposes and have not been analyzed before, during high doses of propofol infusion in rabbits. Materials and Methods: Following ethical committee approval; 2500-3500 grams weight, 3-4 months-old, healthy, male, white 20 New Zealand rabbits were included in the study. The rabbits were premedicated with xsilazine and atropine. After the preparation period including tracheostomy, monitorization, catheterization of the ear arteries and veins and urinary vesical; basal blood samples for biochemical and metabolic parameters included in the study were taken and rabbits were divided into 4 groups, 5 rabbits in each,randomly (Group P, Group PC, Group S, Group SC. For sedation 20 mg/kg/h propofol infusion was given to Group P, 20 mg/kg/h propofol and 100 mg/kg L-carnitine infusions were given simultaneously to Group PC, sevoflurane for sedation was given to Group S, sevoflurane and L-carnitine infusion were given simultaneously to Group SC. Their sedation levels were evaluated every 30 minutes and their vital signs were reported every 15 minutes. Every 2 hours arterial blood gases analysis and every 12 hours electrolytes and metabolic parameters were repeated. Euthanasia with high doses (60 mg/kg of ketamin is performed for rabbits that were alive at the end of 24 hours. Results: All groups were similar in weight, vital parameters, all parameters searched in arterial blood gases, life time, liver enzymes, lactate dehydrogenase, serum electrolytes, creatine kinase and renal function tests (p>0.05. However; amylase levels before death or euthanasia were lower in Group PC compared to other groups;myoglobin and CK-MB levels in Group P were higher compared to other groups; cholesterol levels at 12th hour, before death or euthanasia were higher

  15. The Effect of Creatin and Carnitine Supplementation on 5 kmClassic and 10 km Free Styles Race Performance of Cross Country Skiers

    OpenAIRE

    Ebru ÇETİN

    2004-01-01

    This İnvestigation examined the effect of creatin and carnitine supplementation on 5 km classic and 10 km free styles race performance of competitive cross country skiers.Eighteen highly trained (12 male and 6 female) cross country skiers aged 13-16 years seperated into 3 equal groups. All groups participated in the 5 km classic and 10 km free races styles in Erciyes at 2200m altitude ski center before the carnitine and creatine loading. After the race subjects were seperated into carnitine, ...

  16. Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

    2011-03-01

    The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight, glycemic control, insulin resistance, and inflammatory state in type 2 diabetes mellitus patients. Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >8.0%) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, tumor necrosis factor-α, adiponectin, vaspin, and high-sensitivity C-reactive protein. Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose, postprandial plasma glucose, lipid profile, leptin, tumor necrosis factor-α, and high-sensitivity C-reactive protein compared with sibutramine alone. Furthermore, there was a better improvement of body weight, HbA(1c), fasting plasma insulin, homeostasis model assessment of insulin resistance index, vaspin, and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone. Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Scioli

    Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

  18. [Can the treatment with L-carnitine improve the inflammation in chronic hemodialysis patients?].

    Science.gov (United States)

    Grazi, G; Meriggioli, M; Donati, G

    2004-01-01

    Inflammation in patients on chronic hemodialysis (HD) is related to malnutrition and atherosclerosis; anemia is also often present in these patients. It has been demonstrated that l-carnitina treatment, in addition to reducing the need for erythropoietin (EPO), improves nutritional parameters and cardiac performance. To evaluate the effect of l-carnitine on the inflammatory pathology in patients on chronic HD, we studied 11 patients with no sure signs of malnutrition, flogistic and infective pathologies and with C-reactive protein (CRP) <2 mg/dL. We evaluated at baseline, after 6 and 12 months CRP, serum albumin, hemoglobin (Hb),nPCR and EPO weekly requirement. We observed a reduction in CRP (from 0.88 +/- 0.65 to 0.42 +/- 0.17 mg/dL after 6 months and to 0.50 + 0.36 mg/dL after 12 months), an increase in serum albumin (from 10.9 +/- 1.23 to 2.08 +/- 1.88 and to 11.8 +/- 1.15 g/dL) and an increase in nPCR (from 0.96 +/- 0.09 to 1.15 +/- 0.2 and to 1.16 +/- 0.18 g/kg/die); EPO weekly requirement decreased (from 7363 +/- 2941 to 5909 +/- 3207 units after 6 months and to 5363 +/- 3139 units after 12 months). These results seem to underline a positive effect of l-carnitine on the inflammatory pathology of patients on chronic hemodialytic treatment.

  19. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Benvenga, S; Ruggeri, R M; Russo, A; Lapa, D; Campenni, A; Trimarchi, F

    2001-08-01

    Old studies in animals and unblinded studies in a few hyperthyroid patients suggested that L -carnitine is a periferal antagonist of thyroid hormone action at least in some tissues. This conclusion was substantiated by our recent observation that carnitine inhibits thyroid hormone entry into the nucleus of hepatocytes, neurons, and fibroblasts. In the randomized, double-blind, placebo-controlled 6-month trial reported here, we assessed whether 2 or 4 g/d oral L-carnitine were able to both reverse and prevent/minimize nine hyperthyroidism- related symptoms. We also evaluated changes on nine thyroid hormone-sensitive biochemical parameters and on vertebral and hip mineral density (bone mineral density). Fifty women under a fixed TSH-suppressive dose of L -T(4) for all 6 months were randomly allocated to five groups of 10 subjects each. Group 0 associated placebo for 6 months; groups A2 and A4 started associating placebo (first bimester), substituted placebo with 2 or 4 g/d carnitine (second bimester), and then returned to the association with placebo. Groups B2 and B4 started associating 2 and 4 g/d carnitine for the first two bimesters, and then substituted carnitine with placebo (third bimester). Symptoms and biochemical parameters worsened in group 0. In group A, symptoms and biochemical parameters worsened during the first bimester, returned to baseline or increased minimally during the second bimester (except osteocalcin and urinary OH-proline), and worsened again in the third bimester. In group B, symptoms and biochemical parameters (except osteocalcin and urinary OH-proline) did not worsen or even improved over the first 4 months; they tended to worsen in the third bimester. In both the A and B groups, the two doses of carnitine were similarly effective. At the end of the trial, bone mineral density tended to increase in groups B and A (B > A). In conclusion, L-carnitine is effective in both reversing and preventing symptoms of hyperthyroidism and has a

  20. L-CARNITINE-INDUCED MODULATION OF PLASMA FATTY ACIDS METABOLISM IN HYPERLIPIDEMIC RABBITS

    Directory of Open Access Journals (Sweden)

    Frank Hernández Rosales PhD

    2006-02-01

    mejoramiento del metabolismo de las lipoproteínas. ABSTRACTThe present study was designed to examine whether the hipocholesterolemic effect of L-carnitine supplementation is related with lipoprotein fatty acid metabolism. Fatty acid compositional and cholesterol content changes were measured in lipoproteins of six different groups of rabbits. Group 1, rabbits fed a standard diet; group 2, rabbits fed standard diet plus L-carnitine 80 mg/kg bw; group 3, rabbits fed a 0.5 % cholesterol diet; group 4, rabbits fed a 0.5 % cholesterol diet plus L-carnitine 80 mg/kg b.w. These four groups were fed their diets during 126 days. Group 5 and 6 were fed the same diet as group 4 in a previous period of 126 days, and after this time, group 5 was fed the same diet as group 1, and group 6 fed the same diet as group 2, during a second period of 65 days.However, the progression of hypercholesterolemia was reduced 50 % by L-carnitine administration in those animals fed cholesterol diet. Fatty acid compositional changes in lipoprotein-cholesteryl esters were found in all groups of animals supplemented with L-carnitine. During the standard-fed period the saturated and unsaturated fatty acid ratio was increased in VLDL and HDL particles whereas was decreased in LDL. In the hyperlipidemia progression period the saturated to unsaturated fatty acid ratio in HDL fraction was slightly enhanced and in the VLDL+LDL modified particle was diminished. In the hyperlipidemia regression period, plasma cholesterol level was additionally reduced in a 33 % in the group 6; and the saturated to unsaturated fatty ratio had the same behaviour from that observed in the progression period for HDL and VLDL+LDL particles. A remarkable reduction (75% of aorta atherosclerotic plaques in the group 6 was found. From these results we concluded that L-carnitine, in this experimental model, induces an improved lipoprotein metabolism.

  1. L-carnitine mitigates UVA-induced skin tissue injury in rats through downregulation of oxidative stress, p38/c-Fos signaling, and the proinflammatory cytokines.

    Science.gov (United States)

    Salama, Samir A; Arab, Hany H; Omar, Hany A; Gad, Hesham S; Abd-Allah, Gamil M; Maghrabi, Ibrahim A; Al Robaian, Majed M

    2018-04-01

    UVA comprises more than 90% of the solar UV radiation reaching the Earth. Artificial lightening lamps have also been reported to emit significant amounts of UVA. Exposure to UVA has been associated with dermatological disorders including skin cancer. At the molecular level, UVA damages different cellular biomolecules and triggers inflammatory responses. The current study was devoted to investigate the potential protective effect of L-carnitine against UVA-induced skin tissue injury using rats as a mammalian model. Rats were distributed into normal control group (NC), L-carnitine control group (LC), UVA-Exposed group (UVA), and UVA-Exposed and L-carnitine-treated group (UVA-LC). L-carnitine significantly attenuated UVA-induced elevation of the DNA damage markers 8-oxo-2'-deoxyguanosine (8-oxo-dG) and cyclobutane pyrimidine dimers (CPDs) as well as decreased DNA fragmentation and the activity of the apoptotic marker caspase-3. In addition, L-carnitine substantially reduced the levels of lipid peroxidation marker (TBARS) and protein oxidation marker (PCC) and significantly elevated the levels of the total antioxidant capacity (TAC) and the antioxidant reduced glutathione (GSH) in the skin tissues. Interestingly, L-carnitine upregulated the level of the DNA repair protein proliferating cell nuclear antigen (PCNA). Besides it mitigated the UVA-induced activation of the oxidative stress-sensitive signaling protein p38 and its downstream target c-Fos. Moreover, L-carnitine significantly downregulated the levels of the early response proinflammatory cytokines TNF-α, IL-6, and IL-1β. Collectively, our results highlight, for the first time, the potential attenuating effects of L-carnitine on UVA-induced skin tissue injury in rats that is potentially mediated through suppression of UVA-induced oxidative stress and inflammatory responses. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFα

    Directory of Open Access Journals (Sweden)

    Ingrid M. Garrelds

    1993-01-01

    Full Text Available THE acyl carrier coenzyme A (CoA is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect of 4 days feeding of 300 mg/kg/day of L-carnitine, acetyl Lcarnitine and propionyl L-carnitine on the basal and calcium ionophore (A23187 stimulated release of arachidonic acid metabolites from rat carrageenin elicited peritoneal cells was investigated. There were two series of experiments carried out. In the first, the harvested peritoneal cell population consisted of less than 90% macrophages and additional polymorphonuclear (PMN leucocytes. The basal release of prostaglandin E2 (PGE2, 6-ketoprostaglandin F1α (6-keto-PGF1α and leukotriene B4 (LTB4 was stimulated by all treatments. The A23187 stimulated release of 6-keto-PGF1α and LTB4 was increased by all three compounds. The 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were increased by carnitine treatment. These results suggested that carnitine could modify the macrophage component of an inflammatory site in vivo. In the second series of experiments the harvested cell population was highly purified (>95% macrophages and none of the compounds fed to the rats caused a change of either eicosanoid or TNFα formation. Moreover the 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were not enhanced by any of the compounds tested. It is conceivable that in the first series the increased ratios 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 reflected the effect of carnitine or its congeners on PMN leucocytes rather than on macrophages.

  3. The uptake of tritium-labelled carnitine by monolayer cultures of human fetal muscle and its potential as a label in cytotoxicity studies

    International Nuclear Information System (INIS)

    Cambridge, G.; Stern, C.M.M.

    1981-01-01

    As a novel approach to the investigation of immune responses directed against muscle antigens in inflammatory muscle disease, the use of tritium-labelled carnitine as a selective marker for myotubes in monolayer cultures was investigated. Tritium-labelled carnitine was incubated either with monolayer cultures of human fetal muscle or with syngeneic monolayer cultures of human fetal fibroblasts. The rate of uptake and loss of tritium-labelled carnitine by muscle cultures was compared with that shown by fibroblast cultures; values for the ratio Ksub(m)/Vsub(max) were 3.1 for muscle cultures and 0.46 for fibroblast cultures. Freeze-dried radioautographs of muscle monolayers, previously incubated with tritium-labelled carnitine confirmed the specific intra-tubular localization of the label. Fetal muscle monolayers, previously incubated with tritium-labelled carnitine, were used as targets in long-term cytotoxicity experiments into lymphocyte-mediated myotoxicity. Peripheral blood lymphocytes from patients with inflammatory muscle disease were shown to be myotoxic, but lymphocytes from normal individuals or those with non-inflammatory muscle disease were not. Carnitine-based measures of myotoxicity closely followed the clinical activity of the disease in one patient and the test shows considerable potential as a means of assessing myotube killing by lymphocytes on a per-cell basis. (author)

  4. Protective effects of vitamins E, B and C and L-carnitine in the prevention of cisplatin-induced ototoxicity in rats.

    Science.gov (United States)

    Tokgöz, S Alicura; Vuralkan, E; Sonbay, N D; Çalişkan, M; Saka, C; Beşalti, Ö; Akin, İ

    2012-05-01

    This experimental study aimed to investigate the effects of vitamins E, B and C and L-carnitine in preventing cisplatin-induced ototoxicity. Twenty-five adult, male, Wistar albino rats were randomly allocated to receive intraperitoneal cisplatin either alone or preceded by vitamins B, E or C or L-carnitine. Auditory brainstem response (i.e. hearing thresholds and wave I-IV intervals) and distortion product otoacoustic emissions (i.e. signal-to-noise ratios) were recorded before and 72 hours after cisplatin administration. The following statistically significant differences were seen: control group pre- vs post-treatment wave I-IV interval values (p vitamin E and B groups' I-IV interval values (p vitamin E vs vitamin B and C and L-carnitine groups' hearing thresholds (p vitamin B vs vitamin C and L-carnitine groups' hearing thresholds (p vitamin B and L-carnitine groups (2000 and 3000 Hz; p Vitamins B, E and C and L-carnitine appear to reduce cisplatin-induced ototoxicity in rats. The use of such additional treatments to decrease cisplatin-induced ototoxicity in humans is still under discussion.

  5. Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples From a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark

    DEFF Research Database (Denmark)

    Borch, Luise; Lund, Allan; Wibrand, Flemming

    2011-01-01

    of presymptomatic CPT1A deficiency detected through newborn screening in Denmark with diagnostic levels of carnitine and acylcarnitines in the initial dried blood spot. Levels of plasma-free carnitine and acylcarnitines in follow-up samples were normal, but reverted to diagnostic levels when the patient developed...... clinical symptoms at the age of 8 months. At that time, a diagnosis of CPT1A deficiency was confirmed by sequence analysis of the CPT1A gene revealing homozygosity for a novel c.167C>T variation in exon 3. Enzyme activity measurements showed a relatively mild enzyme defect with a decreased residual enzyme...... activity of 17–25%. We conclude that CPT1A gene testing and/or enzyme assay is mandatory to confirm an abnormal newborn screen suggesting CPT1A deficiency to avoid delayed diagnoses....

  6. Correlation between L-Carnitine and alpha-1, 4-glucosidase activity in the semen of normal, infertile and vasectomized men.

    Science.gov (United States)

    Tremblay, R R; Chapdelaine, P; Roy, R; Thabet, M

    1982-01-01

    The semen content of L-carnitine and of alpha 1, 4-glucosidase has been measured in subjects consulting for evaluation of their fertility. A close correlation (r=0.684) was found between both parameters over the range of azoospermia to normal zoospermia. A significant number of patients with oligo or azoospermia displayed normal values of L-carnitine and of alpha-1, 4-glucosidase while approximately 50% showed levels in the low spectrum of vasectomized men. On the basis of these findings, an obstructive pathology at epididymal or vas deferens level was established by vasography and/or bilateral scrotal exploration in 9 patients with azoospermia. These 2 epididymal markers might thus be useful in the hands of the practicing andrologist who has to determine precisely the site of a dysfunction in the reproductive system which leads to infertility.

  7. Protective Role of L- Carnitine and Zinc against γ-Radiation induced Cardiac and testicular Disorders in Albino Rats

    International Nuclear Information System (INIS)

    Ramadan, F. L.; Abdel-Monem, D.D.; Ismail, N.H.

    2013-01-01

    L-Carnitine is a dipeptide amino acid necessary for fat metabolism, it provides energy by transporting long-chain fatty acids to mitochondria to act as a fuel and it is considered a powerful antioxidant. In addition, zinc is an essential mineral which helps to increase the secretion of male sex hormones and raises the sperm count, so its combination with L-carnitine is useful for the fertility process. The present study aims to evaluate the potency of L-carnitine and zinc as radio- protective and curative agent pre and after exposure to γ-radiation through biochemical, histological, morphological abnormalities of sperms and DNA damage in the sperms induced by γ-irradiation by comet assay. Animals received L-carnitine (LC) and zinc (Zn) orally at the dose 9.45 mg/100 gm body wt./day for successive 20 days and then exposed to whole body gamma radiation at the dose 4 Gy (1 Gy for 4 days, day after day) on the 7th day from treatment with antioxidant. Histological examinations of heart and testis tissues showed that administration of LC and Zn have attenuated radiation induced damage and improved tissues architecture. Moreover, the observed amelioration in the tissues was accompanied by a remarkable decrease of their lipid peroxide levels (malondialdehyde (MDA)), together with an increase in glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities. Hormonal determinations of serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) which carried out for fertility assessment showed that whole body γ-irradiation of rats induced significant decrease in serum testosterone while FSH and LH were significantly increased as compared with control group. On the other hand, irradiation caused significant elevation in the total number of abnormal head, and / or tail of sperms in comparison to the control rats. The comet assay showed that exposure to γ-radiation induced DNA damage of sperms (tail moment values).

  8. Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-11C]propionyl L-carnitine for pharmacokinetic studies

    International Nuclear Information System (INIS)

    Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K.

    1997-01-01

    Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t 1/2 = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [ 11 C]propionyl chloride as labelling agent via 11 C-carboxylation of ethylmagnesium bromide with cyclotron-produced [ 11 C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [ 11 C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [ 11 C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [ 11 C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [ 11 C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [ 11 C]carbon dioxide and hydrolysis. NCA [ 11 C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [ 11 C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [ 11 C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [ 11 C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [ 11 C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [ 11 C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author)

  9. Dietary fat types differently modulate the activity and expression of mitochondrial carnitine/acylcarnitine translocase in rat liver.

    Science.gov (United States)

    Priore, Paola; Stanca, Eleonora; Gnoni, Gabriele Vincenzo; Siculella, Luisa

    2012-10-01

    The carnitine/acylcarnitine translocase (CACT), an integral protein of the mitochondrial inner membrane, belongs to the carnitine-dependent system of fatty acid transport into mitochondria, where beta-oxidation occurs. CACT exchanges cytosolic acylcarnitine or free carnitine for carnitine in the mitochondrial matrix. The object of this study was to investigate in rat liver the effect, if any, of diets enriched with saturated fatty acids (beef tallow, BT, the control), n-3 polyunsaturated fatty acids (PUFA) (fish oil, FO), n-6 PUFA (safflower oil, SO), and mono-unsaturated fatty acids (MUFA) (olive oil, OO) on the activity and expression of CACT. Translocase exchange rates increased, in parallel with CACT mRNA abundance, upon FO-feeding, whereas OO-dietary treatment induced a decrease in both CACT activity and expression. No changes were observed upon SO-feeding. Nuclear run-on assay revealed that FO-treatment increased the transcriptional rate of CACT mRNA. On the other hand, only in the nuclei of hepatocytes from OO-fed rats splicing of the last intron of CACT pre-mRNA and the rate of formation of the 3'-end were affected. Overall, these findings suggest that compared to the BT-enriched diet, the SO-enriched diet did not influence CACT activity and expression, whereas FO- and OO-feeding alters CACT activity in an opposite fashion, i.e. modulating its expression at transcriptional and post-transcriptional levels, respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Plasma fatty acyl-carnitines during 8 Weeks of overfeeding: relation to diet energy expenditure and body composition: the PROOF study.

    Science.gov (United States)

    Bray, George A; Redman, Leanne M; de Jonge, Lilian; Rood, Jennifer; Sutton, Elizabeth F; Smith, Steven R

    2018-01-24

    Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding. Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of overfeeding. Measurements included: body composition by DXA, energy expenditure by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat biopsies, and fat distribution by CT scan. Analysis was done on 5 groups of fatty acyl-carnitines identified by principal components analysis and 6 individual short-chain fatty acyl carnitines. Higher protein intake was associated with significantly lower 8 week levels of medium chain fatty acids and C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived from essential amino acids. In contrast energy and fat intake were only weakly related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week medium chain acyl-carnitines was associated with an increase in sleeping energy expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain fatty acyl-carnitines were related to changes in resting energy expenditure (P = 0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA (P = 0006). Protein intake was the major factor influencing changes in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty acids on the low protein diet. The association of dietary protein and fat intake may explain the changes in energy expenditure and metabolic variables resulting in the observed

  11. Effect of supplementation of lecithin and carnitine on growth performance and nutrient digestibility in pigs fed high-fat diet

    Directory of Open Access Journals (Sweden)

    Arathy Saseendran

    2017-02-01

    Full Text Available Aim: To study the effect of dietary supplementation of lecithin and carnitine on growth performance and nutrient digestibility in pigs fed high-fat diet. Materials and Methods: A total of 30 weaned female large white Yorkshire piglets of 2 months of age were selected and randomly divided into three groups allotted to three dietary treatments, T1 - Control ration as per the National Research Council nutrient requirement, T2 - Control ration plus 5% fat, and T3 - T2 plus 0.5% lecithin plus 150 mg/kg carnitine. The total dry matter (DM intake, fortnightly body weight of each individual animal was recorded. Digestibility trial was conducted toward the end of the experiment to determine the digestibility coefficient of various nutrients. Results: There was a significant improvement (p0.05 among the three treatments on average daily gain, feed conversion efficiency, and nutrient digestibility during the overall period. Conclusion: It was concluded that the dietary inclusion of animal fat at 5% level or animal fat along with lecithin (0.5% and carnitine (150 mg/kg improved the growth performance in pigs than non-supplemented group and from the economic point of view, dietary incorporation of animal fat at 5% would be beneficial for improving growth in pigs without dietary modifiers.

  12. Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine.

    Science.gov (United States)

    Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew; Xu, Alex; Duhart, Helen; Ali, Syed F

    2004-10-01

    The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.

  13. Effects of perfluorodecanoic(PFDA) and perfluorooctanoic (PFOA) acids on hepatic carnitine palmitoyltransferase (CPT) activity in rats

    International Nuclear Information System (INIS)

    Vanden Heuvel, J.P.; Kuslikis, B.I.; Peterson, R.E.

    1990-01-01

    PFDA has been hypothesized to cause a diversion of fatty acids from oxidation toward esterification in rat liver. Normal regulation of this partitioning is exerted by CPT, an enzyme inhibited by several peroxisome proliferators. Effects of the peroxisome proliferators PFDA and PFOA on hepatic mitochondrial fatty acid oxidation and CPT activity were examined. PFDA or PFOA added to isolated rat liver mitochondria in concentrations of 0.2, 2, 20 and 200 μg per mg mitochondrial protein had no effect on CPT activity nor on mitochondrial oxidation of [1- 14 C] palmitoyl-CoA or [1- 14 C] palmitoyl-carnitine (quantitated by 14 CO 2 plus acid soluble 14 C production). Three days after rats were treated with PFDA or PFOA (37.5 or 150 μmol/kg, ip) or vehicle, liver mitochondria were isolated. Mitochondrial oxidation of [1- 14 C] palmitoyl-CoA or [1- 14 C]palmitoyl-carnitine was unaffected by PFDA and PFOA. CPT activity and inhibition of CPT activity by malonyl-CoA was also unaffected by PFDA and PFOA. Therefore, PFDA and PFOA did not have a major inhibitory effect on hepatic mitochondrial oxidation of palmitoyl-CoA or palmitoyl-carnitine, nor did they interfere with hepatic CPT activity either in vitro or in vivo

  14. Development of a sensitive method for a structural elucidation of acyl carnitines by means of GC-MS techniques

    International Nuclear Information System (INIS)

    Altmann, E.

    1999-11-01

    The goal of the present work was to develop a sensitive and reliable method to characterize the urinary acyl carnitines, to further establish it as routine procedure in hospitals, especially in Pedriatic Departments. The determination of the excreted acyl carnitines allows drawing conclusions on errors or deviations in the cellular metabolism. Applying the volatile lactone derivatives of the acyl carnitines various methods of GC/MS technique are compared. With the examined lactones under concern EI mass spectra furnish just a first incomplete information. Frequently the molecular peaks are not sufficiently intense. Yet by means of the retention times, the signals m/z 84, 85 and 144 as ion traces, as well as the characteristic fragmentation helpful information is provided. Concerning the +CI/NH 3 - mass spectra the protonated molecular ions (M + H) + and the usually very intense (M + NH 4 ) + - ions unambiguously render structural assignments. In the case of the - CI/NH 3 - mass spectra the (M-1) and (M-85) ions allow definitive assignments due to their lesser fragmentation tendency. Each of the analytical outcoming can be regarded as leading contribution in helpfully establishing the current method in every clinical hospital. (author)

  15. Imaging mass spectrometry reveals fiber-specific distribution of acetylcarnitine and contraction-induced carnitine dynamics in rat skeletal muscles.

    Science.gov (United States)

    Furuichi, Yasuro; Goto-Inoue, Naoko; Manabe, Yasuko; Setou, Mitsutoshi; Masuda, Kazumi; Fujii, Nobuharu L

    2014-10-01

    Carnitine is well recognized as a key regulator of long-chain fatty acyl group translocation into the mitochondria. In addition, carnitine, as acetylcarnitine, acts as an acceptor of excess acetyl-CoA, a potent inhibitor of pyruvate dehydrogenase. Here, we provide a new methodology for accurate quantification of acetylcarnitine content and determination of its localization in skeletal muscles. We used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to visualize acetylcarnitine distribution in rat skeletal muscles. MALDI-IMS and immunohistochemistry of serial cross-sections showed that acetylcarnitine was enriched in the slow-type muscle fibers. The concentration of ATP was lower in muscle regions with abundant acetylcarnitine, suggesting a relationship between acetylcarnitine and metabolic activity. Using our novel method, we detected an increase in acetylcarnitine content after muscle contraction. Importantly, this increase was not detected using traditional biochemical assays of homogenized muscles. We also demonstrated that acetylation of carnitine during muscle contraction was concomitant with glycogen depletion. Our methodology would be useful for the quantification of acetylcarnitine and its contraction-induced kinetics in skeletal muscles. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine.

    Science.gov (United States)

    Ando, Susumu; Kobayashi, Satoru; Waki, Hatsue; Kon, Kazuo; Fukui, Fumiko; Tadenuma, Tomoko; Iwamoto, Machiko; Takeda, Yasuo; Izumiyama, Naotaka; Watanabe, Kazutada; Nakamura, Hiroaki

    2002-11-01

    A rat dementia model with cognitive deficits was generated by synapse-specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb-Williams maze, AKON-1 maze and a continuous alternation task in T-maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non-matching-to-sample tasks in T-maze. Adenovirus-mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre- and post-lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine-accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx-lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. Copyright 2002 Wiley-Liss, Inc.

  17. Role of L-carnitine in Ameliorating the Cadmium Chloride and/or Irradiation-Induced Testicular Toxicity

    International Nuclear Information System (INIS)

    Ramadan, L.A.

    2003-01-01

    The role of oxidative stress in chronic administration of CdCl2 and/or irradiation toxicity and its prevention by pretreatment with L-carnitine was investigated. Adult male rats were administered with CdCl2 (3 mg/kg S.C. three times a week for three weeks) and /or irradiated at (2 Gy) dose level of gamma radiation. CdCl2 administration and/or irradiation induced cellular damage was indicated by significant decrease in lactate dehydrogenase isoenzyme (LDH-X), glutathione level (GSH) and glutathione peroxidase enzyme activity (GSH-PX) as well as significant increase in malonaldehyde (MDA) in testicular tissues. Administration of L-carnitine (200 mg/kg I.P.) 1 hr before CdCl2 and/or irradiation, ameliorated the decrease in LDH-X, GSH and GSH-PX and the increase in MDA induced by CdCl2 and/or irradiation indicating the prophylactic action of L-carnitine on CdCl2 and /or irradiation toxicity. Various studies have indicated that cadmium is a potent heavy metal carcinogen in experimental animals (Poirier et al., 1983 and Waalkes et al..,1988) and is possibly carcinogenic in human populations exposed either occupationally or environmentally (Bako et al., 1982). Target sites for cadmium carcinogenesis in rodents have been shown to include testes after parenteral exposure (Poirier et al., 1983 and Waalkes et al., 1988) and lung after chronic inhalation (Takenaka et al., 1983)

  18. Protective effect of L-carnitine and L-arginine against busulfan-induced oligospermia in adult rat.

    Science.gov (United States)

    Abd-Elrazek, A M; Ahmed-Farid, O A H

    2018-02-01

    Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L-carnitine and L-arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and busulfan plus L-carnitine (Bus + L-car). After 28 days, the semen was collected from the epididymis and the testes were assessed. Sperm count, motility and velocity were measured by CASA, and smears were prepared for assessment of sperm morphology. Serum and testes supernatants were separated for DNA metabolites, oxidative stress and cell energy parameters. Testes tissues also subjected for caspase-3. The results showed significant improvement in sperm morphology, motility, velocity and count in the groups treated with L-arginine and L-carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in GSH, AMP, ADP, NO and 8-OHDG also recorded. These results are supported by caspase-3. Administration of L-arg and L-car attenuated the cytotoxic effects of busulfan by improving semen parameters, reducing oxidative stress and maintaining cell energy. © 2017 Blackwell Verlag GmbH.

  19. Modulation of synergistic cardiotoxicity of doxorubicin and radiation therapy by propionyl l-carnitine

    International Nuclear Information System (INIS)

    Mansour, H.H.

    2002-01-01

    Combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy. However, the combination of Doxorubicin (DOX) and irradiation (IRR) may be more cardiotoxic than either agent. Propionyl-L-carnitine (PLC) is a naturally occurring derivative of L-carnitine that has been considered in the treatment of many forms of cardiomyopathies. In this study, the possible mechanism (S) whereby PLC couls protect against DOX and/or IRR-induced cardiomyopathy were carried out. Administration of DOX as a single dose (5 mg/Kg) or cumulative dose (15 and 25 mg/kg divided into 3 and 5 equal doses 5 mg/kg each, every other day) resulted in significant and dose dependent increase in serum cardiac enzymes (CPK, GOT and LDH) in rat, MDA level and nitric oxide in heart tissue and dose dependent decrease in the antioxidant enzymes (SOD) and GSHPx). Whole body irradiation (2 Gy) induced similar effect to DOX. Combination of DOX and IRR resulted in marked elevation in cardiac enzymes and MDA level and remarkable decrease in the antioxidant enzymes . PLC (250 mg/kg, for 9 days) before DOX and /or IRR induced significant increase in the activity of SOD and GSHPx and significantly decreased the level of MDA and nitric oxide in rat cardiac tissue and the activity of cardiac enzymes in rat serum. Also, DOX-induced dose dependent increase in AC/FC ratio above the normal value (0.4) in serum and heart tissue. Combination of DOX and IRR increased the ratio. Administration of PLC to DOX and/or IRR resulted in partial reversal of DOX induced increase in the AC/FC ratio except for the highest cumulative dose (25 mg/kg) in serum. Dox induced dose-dependent increase in DOX concentration in serum and heart tissue. Administration of PLC decreased DOX concentration in heart with an increase in DOX concentration in serum. IRR did not alter DOX concentration. Worth mentioning os that PLC had no effect on the antitumor activity of DOX and/ or IRR in solid

  20. [ACTION OF L-CARNITINE, CORVITIN AND THEIR COMBINATION ON FUNCTIONAL STATE OF LIVER IN EXPERIMENTAL MODEL OF REYE SYNDROME IN RATS].

    Science.gov (United States)

    Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

    2017-02-01

    Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats. The study was performed on mature white male Wistar rates with body mass 150-180g. 50 rats were randomly divided into 5 groups (10 rats in each group). The model of Reye syndrome was induced in accordance with A.Vengersky's method. Intraperitoneal administration of 4-pentenoic acid was performed once daily during seven days, the used dosage was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent administration of these drugs. Monotherapy with Corvitin and L-Carnitin successfully improved liver function and equally decreased indicators of hepatocyte's cytolyses and increased levels of glucose and urea. The markers of cholestasis was slightly more improved during use of L-Carnitine. Simultaneous use of both drugs was effective in rats with Reye syndrome, indicators of liver damage normalized and herewith, no mortality outcome was observed. The most pronounced hepatoprotective effect of concurrent administration of L-Carnitine and Corvitin may be due to synergic action of these drugs and such regime can be recommended for correction of liver function during Reye syndrome.

  1. Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Taku Miyagawa

    Full Text Available UNLABELLED: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM sleep abnormalities. A genome-wide association study (GWAS identified a novel narcolepsy-related single nucleotide polymorphism (SNP, which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral L-carnitine for the treatment of narcolepsy, we performed a clinical trial administering L-carnitine (510 mg/day to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02. L-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. L-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 vitality and mental health subscales did not reach statistical significance between L-carnitine and placebo. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN UMIN000003760.

  2. Assessment of pharmacokinetic interaction between piracetam and l-carnitine in healthy subjects.

    Science.gov (United States)

    Mendes, Gustavo D; Zaffalon, Gabriela Traldi; Silveira, Antonio Sérgio; Ramacciato, Juliana Cama; Motta, Rogério Heládio Lopes; Gagliano-Jucá, Thiago; Lopes, Anibal Gil; de Almeida Magalhães, José Cássio; De Nucci, Gilberto

    2016-04-01

    A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

    Directory of Open Access Journals (Sweden)

    Giuseppe Federighi

    Full Text Available Acetyl-L-carnitine (ALC is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

  4. Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

    Science.gov (United States)

    Federighi, Giuseppe; Macchi, Monica; Bernardi, Rodolfo; Scuri, Rossana; Brunelli, Marcello; Durante, Mauro; Traina, Giovanna

    2013-01-01

    Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

  5. Effect of Different Levels of L-Carnitine on the Productive Performance, Egg Quality, Blood Parameters and Egg Yolk Cholesterol in Laying Hens

    Directory of Open Access Journals (Sweden)

    Kazemi-Fard M

    2015-12-01

    Full Text Available This experiment was conducted to investigate the effects of different levels of L-carnitine on productive performance, egg quality and blood parameters in laying hens. Forty-eight Hy-Line W-36 egg Layers were weighed at 90 weeks of age and randomly allocated into 16 cages (three hens per cage. Four dietary treatments were prepared by supplementing L-carnitine (0, 50, 100 and 150 mg/kg of diet to corn-soybean meal diet and offered ad libitum to hens. After two weeks of acclimatization, the eggs were weighed daily and feed intake as well as egg quality traits were measured biweekly. At the end of the experiment, two hens from each cage were selected to determine blood parameters and two eggs from each replicate were collected for cholesterol analysis. Results showed that L-carnitine supplementation at 100 and 150 mg/kg significantly increased egg production and egg mass, but decreased yolk cholesterol content. Laying hens receiving diet containing 50 mg/kg L-carnitine had significantly higher Hough unit, but lower progesterone than the hens fed control diet (P < 0.05. The results of this study showed that supplementing hens' diet with L-carnitine had beneficial effects on productive performance and decreased yolk cholesterol concentration; so it can be used as an effective supplement in the diet of laying hens.

  6. Phase II Randomized Study of Plitidepsin (Aplidin, Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma

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    Patrick Schöffski

    2009-03-01

    Full Text Available This randomized phase II study evaluated two schedules of the marine compound Plitidepsin with or without co-administration of L-carnitine in patients with renal cell carcinoma. Patients had adequate performance status and organ function.The primary endpoint was the rate of disease control (no progression at 12 weeks (RECIST.Other endpoints included the response rate and time dependent efficacy measures.The trial also assessed the efficacy of L-carnitine to prevent Plitidepsin-related toxicity. The two regimes given as 24 hour infusion every two weeks showed hints of antitumoral activity. Disease control at 12 weeks was 15.8% in Arm A (5mg/m2, no L-carnitine and 11,1% in Arm B (7mg/m2 with L-carnitine. Two partial responses were observed in Arm A (19 patients, none in Arm B (20 patients. Both schedules had the same progression-free interval (2.1 months.The median overall survival was 7.0 and 7.6 months.The safety profile was similar in both arms of the trial and adverse events were mainly mild to moderate (NCI CTC version 2.0. Increasing the dose to 7mg/m2 did not increase the treatment efficacy but the incidence of transaminase and CPK elevations and serious AEs. Coadministration of L-carnitine did not prevent muscular toxicity or CPK-elevation associated with Plitidepsin.

  7. Synthesis, purification, and time-dependent disposition studies of 9- or 10-mono-iodostearic acid and 9- and 10-mono-iodostearyl carnitine

    International Nuclear Information System (INIS)

    Reed, K.W.

    1985-01-01

    The purpose of this investigation was to evaluate the potential use of radiolabeled 9- or 10-mono-iodostearyl carnitine as a perfusion and metabolic imaging agent for the heart. Radiochemical purity was achieved and determined by the use of silica gel and/or anion exchange resin chromatography. Radiochemical yields of 45-63 and 4% were obtained for the fatty acid and carnitine ester, respectively. Male albino mice were sacrificed at 2, 5, 7, 10, 15, 20, 30, and 50 minutes post-injection with either 125 I 9- or 10-mono-iodostearic acid or 9- or 10-mono-iodostearyl (-) carnitine. The lungs, liver heart, kidney, spleen, pancreas, small intestine, stomach, thyroid, blood, fat, and skeletal muscle tissue were excised and assayed for levels of radioactivity in a NaI crystal well counter. The very low target-to-nontarget ratios obtained with 125 I 9- or 10-mono-iodostearyl carnitine in mice strongly suggest that radioiodinated 9- or 10-mono-iodostearyl carnitine is not suitable for use as a myocardial imaging agent. However, radioiodinated 9- or 10-mono-iodostearic acid showed promise as a myocardial imaging agent and may warrant further investigation

  8. Survey of Synergistic Effect of L-carnitine with Glutamine on Body Composition and Dietary Intake in Soccer Players: A Double-blind, Randomized Clinical Trial

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    Mohammad Hozoori

    2016-10-01

    Full Text Available Background: The present study was conducted to investigate the possible effects of L-carnitine and glutamine and their synergistic effects on male soccer athletes. Methods: 28 male soccer players (21.1 ± 0.7 y were enrolled in a randomized pre and post intervention, double-blind design. Before the intervention, their performances were assessed by Bruce protocol, and their body composition was measured with the body composition analyzer. Then, athletes were randomly allocated into four groups: 2 g L-glutamine, 2 g L-carnitine, 2 g L-carnitine + 2 g L-glutamine and placebo. Supplements were prescribed for 21 days and after three weeks, athletes' performances and body composition were re-evaluated. Results: The results showed that body weight, body fat percentage, lean muscle mass, and dietary intake made no significant changes in different groups of athletes. In between groups comparison, results did not significantly change in any performance indices. However, in L-carnitine supplement group, the results of pre and post intervention showed that the running distance and maximal oxygen uptake (VO2max increased significantly while the subjective sense of fatigue decreased significantly. Conclusions: Based on our findings, a three-week prescription of separateor combined glutamine and L-carnitine, had no effects on body composition or dietary intake in soccer players. But, the athletes' energy intake was more than the one reported in other studies. Although further studies are required to assess these effects on athletic performance.

  9. Effects of a therapeutic lifestyle change diet and supplementation with Q10 plus L-carnitine on quality of life in patients with myocardial infarction: A randomized clinical trial

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    Mohammad Hossein Sharifi

    2017-03-01

    Conclusion: Both TLC diet and supplementation with Q10 and L- carnitine had a positive effect on the physical and emotional subscales of MacNew questionnaire and may improve post-MI prognosis. Based on the results, combination of Q10 plus L-carnitine and TLC die can be a potential intervention for improving QoL and secondary prevention.

  10. Dynamic monitoring of plasma amino acids and carnitine during chemotherapy of patients with alimentary canal malignancies and its clinical value

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    Wang XY

    2015-08-01

    Full Text Available Xiaoyu Wang,1 Jiaqi Wang,2 Zhenghua Wang,1 Qingjun Wang,1 Hua Li1 1Second Ward of Oncology Department, 2Traditional Chinese Medicine Department, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, People’s Republic of ChinaObjective: The aim of this study was to observe the plasma amino acid and carnitine characteristics in patients with metastatic gastrointestinal malignancies during chemotherapy and to identify markers for the early diagnosis and evaluation of adverse reactions and prognosis of the digestive tract malignant tumor patients.Methods: Blood samples of 30 patients with metastatic gastrointestinal malignancies were collected at four time points: before chemotherapy, the first day after chemotherapy (+1 day, bone marrow depression period (+14 days, and hematopoietic recovery period (+21 days. The plasma amino acids and carnitine from those 30 patients were determined by high-performance liquid chromatography–tandem mass spectrometry method. Simultaneously, the levels of 21 amino acids were detected in 30 healthy individuals, who were considered as control. Biochemical indexes were also detected at four time points, adverse reactions were recorded during the chemotherapy process, and patients were followed up for 1 year to observe time to progression (TTP and progression-free survival (PFS.Results: Compared to healthy people in the control group, patients with malignancies showed significantly increased levels of plasma amino acids such as Arg, Asp, Cit, Gly, Orn, Tyr, Val, and carnitine (such as C2. The levels of compounds such as C3, Asn, Leu, Lys, Pip, Pro, C0, C5:1 decreased significantly before chemotherapy. The levels of Cit, Cys, Lys, Pro, Tyr, Val, C0, and C2 decreased significantly on the second day of chemotherapy (+1 day, whereas the level of C3 increased significantly. During myelosuppression (+14 days, the levels of Asp, Cit, Met, and Orn were observed to still decrease significantly, whereas the

  11. Effect of methylglyoxal bis(guanylhydrazone) on hepatic, heart and skeletal muscle mitochrondrial carnitine palmitoyltransferase and. beta. -oxidation of fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Brady, L.J.; Brady, P.S.; Gandour, R.D.

    1986-05-01

    Methylglyoxal bis(guanylhydrazone) (MGBG) is an antileukemic agent and polyamine analog which inhibits S-adenosyl methionine decarboxylase. However, MGBG also produces mitochondrial structural damage and inhibition of ..beta..-oxidation. The present experiments were designed to determine if MGBG acts via carnitine palmitoyltransferase-A (CPT-A) inhibition. Liver, heart and skeletal muscle mitochondria were isolated from rats following a 24 h fast. MGBG was competitive with 1-carnitine. The MGBG CPT-A Ki were (mM): liver, 5.0 +/- 0.6 (n = 15); heart, 3.2 +/- 1.2 (n = 3); skeletal muscle, 2.8 +/- 1.0 (n = 3). Lysis of hepatic mitochondria with Triton X-100 yielded a Ki of 4.0 +/- 2.0. Purified hepatic CPT was also sensitive to MGBG inhibition (Ki = 4.5 mM). Spermine and spermidine, which are structurally similar to MGBG, did not inhibit CPT or acid-soluble product formation from 1-(/sup 14/C)-palmitoyl-CoA. MGBG inhibited mitochondrial state 3 oxidation rates of palmitoyl-CoA and palmitoylcarnitine, as well as of glutamate. However, the fatty acid substrates were considerably more sensitive than glutamate to MGBG inhibition. MGBG also increased hepatic mitochondrial aggregation which was reversed by 1-carnitine. Fluorescence polarization, using diphenylhexatriene as a probe, indicated that MGBG increased membrane rigidity in a dose dependent manner. This effect was not reversed by 1-carnitine. The authors conclude that MGBG exhibits competitive competition with 1-carnitine for CPT. However, MGBG also exhibits a number of effects which may be mediated through membrane interaction and which are not necessarily reversed by carnitine.

  12. Effect of methylglyoxal bis(guanylhydrazone) on hepatic, heart and skeletal muscle mitochrondrial carnitine palmitoyltransferase and β-oxidation of fatty acids

    International Nuclear Information System (INIS)

    Brady, L.J.; Brady, P.S.; Gandour, R.D.

    1986-01-01

    Methylglyoxal bis(guanylhydrazone) (MGBG) is an antileukemic agent and polyamine analog which inhibits S-adenosyl methionine decarboxylase. However, MGBG also produces mitochondrial structural damage and inhibition of β-oxidation. The present experiments were designed to determine if MGBG acts via carnitine palmitoyltransferase-A (CPT-A) inhibition. Liver, heart and skeletal muscle mitochondria were isolated from rats following a 24 h fast. MGBG was competitive with 1-carnitine. The MGBG CPT-A Ki were (mM): liver, 5.0 +/- 0.6 (n = 15); heart, 3.2 +/- 1.2 (n = 3); skeletal muscle, 2.8 +/- 1.0 (n = 3). Lysis of hepatic mitochondria with Triton X-100 yielded a Ki of 4.0 +/- 2.0. Purified hepatic CPT was also sensitive to MGBG inhibition (Ki = 4.5 mM). Spermine and spermidine, which are structurally similar to MGBG, did not inhibit CPT or acid-soluble product formation from 1-[ 14 C]-palmitoyl-CoA. MGBG inhibited mitochondrial state 3 oxidation rates of palmitoyl-CoA and palmitoylcarnitine, as well as of glutamate. However, the fatty acid substrates were considerably more sensitive than glutamate to MGBG inhibition. MGBG also increased hepatic mitochondrial aggregation which was reversed by 1-carnitine. Fluorescence polarization, using diphenylhexatriene as a probe, indicated that MGBG increased membrane rigidity in a dose dependent manner. This effect was not reversed by 1-carnitine. The authors conclude that MGBG exhibits competitive competition with 1-carnitine for CPT. However, MGBG also exhibits a number of effects which may be mediated through membrane interaction and which are not necessarily reversed by carnitine

  13. The Protective Effect of Proponyl-L-Carnitine Against Ultrastructural Alterations in Cardiac Muscle of Irradiated and / or diabetic Rats

    International Nuclear Information System (INIS)

    Abu Nour, S.M.; Abdel-Azeem, M.G.; El-Nashar, D.E.M.

    2011-01-01

    Heart dysfunction in chronic diabetes has been observed to be associated with depressed myofibrillar adenosine triphosphatase activities. Oxidative stress a factor implicated in the heart injury may contribute towards some of these alterations. The present study was designed to evaluate the efficacy of L-carnitine on gamma radiation and diabetes induced oxidative damage in the heart by investigating alterations in the ultrastructural level. Streptozotocin was intraperitoneally injected (i.p) to rats at a dose of 28 mg/Kg b.wt / day for 2 weeks pre-irradiation. In irradiated groups, animals were exposed to 6.5 Gy whole body gamma radiation. L-carnitine was intraperitoneally injected (i.p) to rats at a dose of 250 mg/Kg b.wt/day for 2 weeks pre-irradiation. Animals were sacrificed on the 7th day after irradiation. The results demonstrated that the whole body exposure of rats to ionizing radiation induce oxidative stress which showed alterations on the ultrastructural level included dis organization with mayofibrillolysis relatively intact z-band (Z), fibrosis, swollen mitochondria, apoptotic nuclei and thickened walls of capillaries. In diabetic rats cardio muscle focal loss of myofilaments, also swelling of mitochondria and rupture of sacroplasmic reticulum, apoptotic nuclei with dilation of capillaries were evident. Administration of L-carnitine pre-irradiation has improved the ultrastructural alterations of the heart tissue. It is proposed that the oxidative stress is associated with a deficit in the status of the antioxidant defense system which may play a critical role in subcellular remodeling, calcium-handling abnormalities and subsequent diabetic cardiomyopathy

  14. Retinal Pigment Epithelial Cell Culture and Cooperation of L-carnitine in Reducing Stress Induced Cellular Damage

    International Nuclear Information System (INIS)

    Shamsi, Farrukh A.; Al-Rajhi, Ali A.; Athmanathan, S.; Boulton, M.; Chaudhry, Imtiaz A.

    2006-01-01

    Purpose was to show that L-carnitine (LC) is capable of reducing non-oxidative stress in the retinal pigment epithelial cells (RPE) of the human eye. The RPE cells were cultured from donor eyes, obtained immediately after post-mortem. The interaction between bovine serum albumin (BSA) and non-oxidative (sodium hydroxide and methyl methane sulphonate) stress-inducers was observed by recording the change in the absorption profiles of the interacting molecules after incubation in light for 5 hours and after treatment with LC. The isolated and cultured RPE cells from the human eyes were treated with sodium hydroxide or methyl methane sulphonate and/or LC for 5 hours under light, and the qualitative effect on cell morphology after treatment was analyzed by staining cells with Giemsa and visualization by light microscopy. The cell morphology was also qualitatively analyzed by scanning electron microscopy (SEM). L-carnitine and stress-inducers interact with BSA and bring about changes in the spectral profile of the interacted molecules. Light microscopy as well as SEM show that the changes in the cellular morphology, induced by 100 uM concentrations of non-oxidative stress-inducers, are considerably reduced in the presence of 100 uM LC. However, L-carnitine alone does not cause any qualitative damage to the cell morphology during incubation under similar conditions. The results give a preliminary indication that LC has ability to reduce the changes brought about by the non-oxidative stress-inducers in the RPF cells in culture. (author)

  15. Distinct effects of ketamine and acetyl l-carnitine on the dopamine system in zebrafish

    Science.gov (United States)

    Robinson, Bonnie L.; Dumas, Melanie; Cuevas, Elvis; Gu, Qiang; Paule, Merle G.; Ali, Syed F.; Kanungo, Jyotshna

    2016-01-01

    Ketamine, a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1–0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reversed 2 mM ketamine-induced reduction in HVA levels. With ALCAR alone, the expression of genes encoding the DA metabolizing enzymes, MAO (monoamine oxidase) and catechol-O-methyltransferase (COMT), was not affected. However, ketamine altered MAO mRNA expression, except at the 0.1 mM dose. COMT transcripts were reduced in the 2 mM ketamine-treated group. These distinct effects of ketamine and ALCAR on the DA system may shed some light on the mechanism on how ketamine can work as an anti-depressant, especially at sub-anesthetic doses that do not affect DA metabolism and suppress MAO gene expression. PMID:26898327

  16. PGC-1{beta} regulates mouse carnitine-acylcarnitine translocase through estrogen-related receptor {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Gacias, Mar; Perez-Marti, Albert; Pujol-Vidal, Magdalena; Marrero, Pedro F. [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain); Haro, Diego, E-mail: dharo@ub.edu [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain); Relat, Joana [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer The Cact gene is induced in mouse skeletal muscle after 24 h of fasting. Black-Right-Pointing-Pointer The Cact gene contains a functional consensus sequence for ERR. Black-Right-Pointing-Pointer This sequence binds ERR{alpha} both in vivo and in vitro. Black-Right-Pointing-Pointer This ERRE is required for the activation of Cact expression by the PGC-1/ERR axis. Black-Right-Pointing-Pointer Our results add Cact as a genuine gene target of these transcriptional regulators. -- Abstract: Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficiency causes a variety of pathological conditions, such as hypoketotic hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and it can be fatal in newborns and infants. Here we report that expression of the Cact gene is induced in mouse skeletal muscle after 24 h of fasting. To gain insight into the control of Cact gene expression, we examine the transcriptional regulation of the mouse Cact gene. We show that the 5 Prime -flanking region of this gene is transcriptionally active and contains a consensus sequence for the estrogen-related receptor (ERR), a member of the nuclear receptor family of transcription factors. This sequence binds ERR{alpha}in vivo and in vitro and is required for the activation of Cact expression by the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1/ERR axis. We also demonstrate that XTC790, the inverse agonist of ERR{alpha}, specifically blocks Cact activation by PGC-1{beta} in C2C12 cells.

  17. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

    2017-03-01

    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

  18. Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

    Science.gov (United States)

    De Marchi, S; Zecchetto, S; Rigoni, A; Prior, M; Fondrieschi, L; Scuro, A; Rulfo, F; Arosio, E

    2012-10-01

    Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p < 0.05). Post-ischemic peak flow with laser-Doppler flow increased after PLC. TcPO2 increased, while TcPCO2 decreased after PLC; CO2 production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

  19. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    International Nuclear Information System (INIS)

    Bevilacqua, M.; Vago, T.; Norbiato, G.

    1991-01-01

    Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine [ 3 H]-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca 2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca 2+ -containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37 degree C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37 degree C decreased the affinity of the binding; this effect was counteracted by the addition of Ca 2+ to the medium. This result was consistent with a competition between Ca 2+ and PC. The effect of PC incubation at 4 degree C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca 2+

  20. Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

    Science.gov (United States)

    Lapi, Dominga; Sabatino, Lina; Altobelli, Giovanna Giuseppina; Mondola, Paolo; Cimini, Vincenzo; Colantuoni, Antonio

    2010-01-01

    Propionyl-l-carnitine (pLc) exerts protective effects in different experimental models of ischemia-reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster cheek pouch preparation. The hamster cheek pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length, and capillary red blood cell velocity (V(RBC)) were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS) formation were determined by thiobarbituric acid-reactive substances (TBARS) and 2'-7'-dichlorofluorescein (DCF), respectively. In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and V(RBC) decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion, and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF) abolished pLc effects. Topical application of pLc on cheek pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase.

  1. Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

    Directory of Open Access Journals (Sweden)

    Dominga Lapi

    2010-10-01

    Full Text Available Background and Purpose Propionyl-L-carnitine (pLc exerts protective effects in different experimental models of ischemia-reperfusion (I/R. The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster check pouch preparation. Methods The hamster check pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length and capillary red blood cell velocity (VRBC were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS formation were determined by thiobarbituric acid-reactive substances (TBARS and 2’-7’-dichlorofluorescein (DCF, respectively. Results In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and VRBC decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF abolished pLc effects. Topical application of pLc on check pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. Conclusions pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase.

  2. Effect of L-carnitine on fatty acid oxidation of the muscle in hemodialysis patients

    International Nuclear Information System (INIS)

    Siami, G.; Clinton, M.; Borum, P.

    1986-01-01

    Muscle weakness is a major cause of morbidity in end stage renal disease (ESRD) patients on long term hemodialysis (HD). Carnitine (C) is important for transport of fatty acids into mitochondria. The kidney is a major site of C biosynthesis which may be compromised in ESRD. C is lost during dialysis and is reduced in plasma and muscle. Although the cause of muscle weakness is multifactorial, the effect of supplemental C was tested on a group of ESRD patients on HD. C (1 gm I.V. 3 x/wk) or placebo was given to HD patients for 6 months. Muscle biopsies were obtained before and after C supplementation and from control subjects. Muscle pathology was examined by histochemical light microscopy. Fatty acid oxidation (FAO) by homogenate of the biopsied muscle was measured using [ 14 C] palmitate. Plasma aluminum (AL) and parthyroid hormone (PTH) were also measured and patients were evaluated for the degree of muscle weakness. All Pts had abnormal muscle pathology and C supplementation did not improve it. FAO by 3 HD Pts who had received placebo was 639 +/- 285 (S.D.) dpm/mg protein while control subjects were 1487 +/- 267 and was statistically different (p < .003). FAO by 8 HD Pts receiving C was not different from placebo. Addition of C in vitro stimulated FAO 70 to 80%, but there was not difference between groups. The degree of FAO was inversely correlated with the severity of the muscle pathology, and was directly correlated with the concentration of C in muscle. Pts with high plasma AL had lower FAO, but there was no correlation between FAO and PTH

  3. Effects of Supplementation Time of L-Carnitine and Garlic Powder on Performance and Carcass Characteristics of Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Ali Khatibjoo

    2016-08-01

    Full Text Available Introduction Carnitine has several roles in lipid oxidation, immunomodulation function and enhancing antibody responses. L-carnitine has been found to exhibit immunomodulatory effects. It enhances serum primary antibody response to sheep red blood cells (SRBC and subsequent humoral immunity using 100 mg L-carnitine/ kg diet compared with control group in Leghorn chickens (Deng et al., 2006. It was reported that only the immediate effects of dietary carnitine on immunocompetence is known while comparing long and short-term effects on early life on the immune system of broiler chickens is unknown. The organic allyl sulfur components in garlic (mainly allicin were implicated to mediate its biological activity. The biological activities of these compounds may be related to their SH modification and antioxidant properties (Prasad et al., 1996. AGE treatment prevented the reduction of the antibody production response in thymectomized mice and improved the thymectomy-induced deterioration of learning behaviors in passive avoidance performance and in a spatial memory task (Zhang et al., 1998. Materials and Methods Four hundred Arian one-day-old broiler chicks were used. This experiment was conducted in order to consider the effects of L-Carnitine and garlic powder on broiler chicken performance, blood metabolites and carcass characteristics in a 2×5 factorial arrangement in randomized complete design with 5 dietary treatments, 4 replicates and 12 birds in each and two periods: short (first 3 weeks and long time (total production period. Dietary treatments were 1 Basal diet (BD: no supplementation, 2 ration having 0.02% flavomycin (positive control, 3 ration having 1.5% garlic powder, 4 ration having 0.025% L-Carnitine and 5 ration having 0.025% L-Carnitine plus 1.5% garlic powder. The birds were kept under conventional conditions for vaccination, temperature, ventilation, and lighting based on Ross catalogue recommendations. Standard management

  4. Patients with medium-chain acyl-coenzyme a dehydrogenase deficiency have impaired oxidation of fat during exercise but no effect of L-carnitine supplementation

    DEFF Research Database (Denmark)

    Madsen, K L; Preisler, N; Orngreen, M C

    2013-01-01

    It is not clear to what extent skeletal muscle is affected in patients with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). l-Carnitine is commonly used as a supplement in patients with MCADD, although its beneficial effect has not been verified.......It is not clear to what extent skeletal muscle is affected in patients with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). l-Carnitine is commonly used as a supplement in patients with MCADD, although its beneficial effect has not been verified....

  5. The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins

    Directory of Open Access Journals (Sweden)

    Michael N. Davies

    2016-01-01

    Full Text Available Lysine acetylation (AcK, a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT, an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK.

  6. Characteristics of separation of carnitine and metal ions in cheese whey model solution by loose reverse osmosis membrane

    Energy Technology Data Exchange (ETDEWEB)

    Xu, J.; Echizen, H.; Xing, X.; Yamamoto, S.; Unno, H. [Tokyo Institute of Technology, Tokyo (Japan)

    1996-04-20

    Aiming at recovering carnitine from cheese whey by using loose reverse osmosis membranes, rejection characteristics of several components in the whey were examined by using model solutions. An electroneutral membrane was found to be most effective for the separation. The rejection of carnitine was above 0.95 independent of the pH of solutions, while monovalent metal ions showed low rejections of 0.1-0.3. On the other hand, the rejections of divalent metal ions deceased with increase of the pH, and reached a minimum of about 0.5. As a result, mono-and divalent metal ions could be removed simultaneously by adjusting the pH of the feed solutions. To clarify the effect of pH on the rejection the permeate of MgCl2 aqueous solution was examined. The rejections of MgCl2 were greatly affected by the pH and showed the same tendency as the mixed station. The effect of the pH on permeation of electrolyte was considered to be caused mainly by the adsorption of ions on the membrane. 16 refs., 6 figs., 2 tabs.

  7. Inhibition by etomoxir of rat liver carnitine octanoyltransferase is produced through the co-ordinate interaction with two histidine residues.

    Science.gov (United States)

    Morillas, M; Clotet, J; Rubí, B; Serra, D; Ariño, J; Hegardt, F G; Asins, G

    2000-10-15

    Rat peroxisomal carnitine octanoyltransferase (COT), which facilitates the transport of medium-chain fatty acids through the peroxisomal membrane, is irreversibly inhibited by the hypoglycaemia-inducing drug etomoxir. To identify the molecular basis of this inhibition, cDNAs encoding full-length wild-type COT, two different variant point mutants and one variant double mutant from rat peroxisomal COT were expressed in Saccharomyces cerevisiae, an organism devoid of endogenous COT activity. The recombinant mutated enzymes showed activity towards both carnitine and decanoyl-CoA in the same range as the wild type. Whereas the wild-type version expressed in yeast was inhibited by etomoxir in an identical manner to COT from rat liver peroxisomes, the activity of the enzyme containing the double mutation H131A/H340A was completely insensitive to etomoxir. Individual point mutations H131A and H340A also drastically reduced sensitivity to etomoxir. Taken together, these results indicate that the two histidine residues, H131 and H340, are the sites responsible for inhibition by etomoxir and that the full inhibitory properties of the drug will be shown only if both histidines are intact at the same time. Our data demonstrate that both etomoxir and malonyl-CoA inhibit COT by interacting with the same sites.

  8. Analysis of amino acids and acyl carnitine profiles in low birth weight, preterm, and small for gestational age neonates.

    Science.gov (United States)

    Liu, Qian; Wu, Jing; Shen, Wen; Wei, Ran; Jiang, Jianhui; Liang, Jinqun; Chen, Min; Zhong, Mei; Yin, Aihua

    2017-11-01

    To analyze the amino acids (AA) and acyl carnitine (AC) profiles in dry blood spot (DBS) specimens of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA), and to compare the concentration difference of AA and AC with those without above. This is a retrospectively study. Eight thousand nine hundred and seventy-nine uncomplicated pregnant newborns were enrolled into the study. DBS were collected on the third day of life, and concentrations of 11 types of AA, free carnitine and 30 types of AC were detected by using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS). Shapiro-Wilk test and Kruskal-Wallis rank test were applied in statistical analysis. Concentrations of most AA and AC in infants born in SGA were significantly higher than those in non-SGA group, while lower in LBW and PTB groups than those in non-LBW and non-PTB groups (p < 0.05). The difference of concentration of AA and AC in the subgroups suggested there may be a dysutilization of AA and AC in SGA, but an inborn insufficient of AA and AC in LBW and PTB neonates.

  9. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Badrasawi, M; Shahar, Suzana; Zahara, A M; Nor Fadilah, R; Singh, Devinder Kaur Ajit

    2016-01-01

    Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine ( P <0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.

  10. Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases.

    Science.gov (United States)

    Merra, Giuseppe; Gasbarrini, Giovanni; Laterza, Lucrezia; Pizzoferrato, Marco; Poscia, Andrea; Scaldaferri, Franco; Arena, Vincenzo; Fiore, Francesca; Cittadini, Achille; Sgambato, Alessandro; Franceschi, Francesco; Gasbarrini, Antonio

    2012-09-28

    To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant

  11. Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

    DEFF Research Database (Denmark)

    Rajakumar, Chandheeb; Ban, Matthew R; Cao, Henian

    2009-01-01

    Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty acid metabolism. Previously, a loss of function mutation, namely c.1436 CT (p.P479L), was reported in CPT1A in the homozygous state in Canadian aboriginal male with presumed CPT1A deficiency. In order to determine...

  12. Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo

    NARCIS (Netherlands)

    Wessels, B.; van den Broek, N.M.A.; Ciapaite, J.; Houten, S.M.; Wanders, R.J.A.; Nicolay, K.; Prompers, J.J.

    2015-01-01

    Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid

  13. Comparative effects of dietary corn oil, safflower oil, fish oil and palm oil on metabolism of ethanol and carnitine in the rat.

    Science.gov (United States)

    Sachan, Dileep S; Yatim, Ayub M; Daily, James W

    2002-06-01

    This study was launched to determine comparative effects of corn oil (CO), safflower oil (SO), fish oil (FO) and palm oil (PO) on carnitine status and ethanol metabolism in rats. Twenty-four male Sprague-Dawley rats (300 g bw) were randomly divided into four groups (n = 6) and fed a semisynthetic diets containing fat as oils listed above. Blood and 24 hour urine samples were collected before and after dietary treatment and acute ethanol administration. Samples were analyzed for blood-ethanol concentration (BEC) and carnitine species. The diets containing FO and PO retarded ethanol metabolism compared to the diets containing CO and SO. The effect of these dietary fats on carnitine species in plasma and urine was varied before and after dietary treatment and following a single oral ethanol dose. The liver carnitine content was higher in the PO group after dietary and ethanol treatment. It is concluded that attenuation of ethanol clearance was related to unique fatty acid makeup of the oils that in part may be attributed to the composite ratio of saturated to unsaturated fatty acids in the oils.

  14. Changes in fatty acid concentrations in tissues of African catfish, Clarias gariepinus, as a consequence of dietary carnitine, lysine and lipid supplements

    NARCIS (Netherlands)

    Ozorio, E.O.A.; Uktolseja, J.L.A.; Huisman, E.A.; Verreth, J.A.J.

    2001-01-01

    A study was undertaken to examine the effect of different dietary carnitine (200 and 1000 mg/kg diet) and fat (90 and 190 g/kg diet) supplementation on growth and fatty acid concentrations of fish fed either with a low- (13 g/kg) or a high-lysine (21 g/kg) diet. African catfish (22?7 g/fish),

  15. Acetyl-L-Carnitine as an Adjunctive Therapy in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Placebo-Controlled Trial

    Science.gov (United States)

    Abbasi, Seyed-Hesameddin; Heidari, Shahram; Mohammadi, Mohammad-Reza; Tabrizi, Mina; Ghaleiha, Ali; Akhondzadeh, Shahin

    2011-01-01

    The objective of this study was to test whether a previous observed Acetyl-L-carnitine (ALC) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This was a six-week, randomized clinical trial undertaken in an outpatient child and adolescent…

  16. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome

    NARCIS (Netherlands)

    Smits, L.P.; Kootte, R.S.; Levin, E.; Prodan, A.; Fuentes, S.; Zoetendal, E.G.; Wang, Z; Levison, B.S.; Cleophas, M.C.P.; Kemper, E.M.; Dallinga-Thie, G.M.; Groen, A.K.; Joosten, L.A.B.; Netea, M.G.; Stroes, E.S.; Vos, W.M. de; Hazen, S.L.; Nieuwdorp, M.

    2018-01-01

    BACKGROUND: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly

  17. Effect of vegan fecal microbiota transplantation on carnitine- and choline-derived trimethylamine-N-oxide production and vascular inflammation in patients with metabolic syndrome

    NARCIS (Netherlands)

    Smits, Loek P.; Kootte, Ruud S.; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G.; Wang, Zeneng; Levison, Bruce S.; Cleophas, Maartje C.P.; Kemper, E.M.; Dallinga-Thie, Geesje M.; Groen, Albert K.; Joosten, Leo A.B.; Netea, Mihai G.; Stroes, Erik S.G.; Vos, de Willem M.; Hazen, Stanley L.; Nieuwdorp, Max

    2018-01-01

    Background--Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly

  18. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Samimi, Mansooreh; Jamilian, Mehri; Ebrahimi, Faraneh Afshar; Rahimi, Maryam; Tajbakhsh, Banafsheh; Asemi, Zatollah

    2016-06-01

    Limited data are available for evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS. In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the beginning and the end of the study to quantify parameters of glucose homoeostasis and lipid concentrations. At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2·7 ± 1·5 vs +0·1 ± 1·8 kg, P weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone. © 2015 John Wiley & Sons Ltd.

  19. The effect of acute L-Carnitine supplementation on the blood lactate, glucose, VO2max and power in trained men: a brief report

    Directory of Open Access Journals (Sweden)

    Arazi H

    2013-04-01

    Full Text Available Background: Probably L-Carnitine can induce increasing of Pyruvate dehydrogenase activity, decreasing of lactic acid production and performance improvements due to the reinforcement of long chain fatty acid oxidation and stabilize of Coenzyme A (CoASH to free Coenzyme A (COA. Based on this, the aim of this study was to investigate the effect of acute L-Carnitine supplementation on blood lactate, glucose, VO2max and anaerobic power in trained men.Methods: Sixteen trained men (aged 19-23 volunteers from University of Guilan, facul-ty of Physical Education and Sport Sciences participated as subjects in this investiga-tion. Subjects divided to aerobic (A and anaerobic (An group randomly. In a double blind design, subjects participated in two separated tests by one week. Subjects ingested 3 grams of L-Carnitine supplementation or placebo (maltodextrin 90 minute before aerobic and anaerobic exercise. For aerobic activity used shuttle run 20 meter and for anaerobic activity used RAST test. Blood samples were collected 5 minute prior at rest and 4 minute post tests. Participants were asked in the morning to obtain fasting blood samples and perform tests. A t-test was used to detect differences between supplementa-tion and placebo groups in each exercise.Results: L-Carnitine group ((A 141.25±20.62 and (An 145.38±55.47 significantly had lower lactate concentration than placebo ((A 151.00±20.85 and (An 152.50±28.59 after tests (P≤0.05. L-Carnitine group ((A 136.00±19.74 and (An 115.50±13.64 had significa-ntly higher blood glucose compared to placebo ((A 121.62±15.65 and (An 110.12±12.63 too (P≤0.05. Also, VO2max, mean and maximum anaerobic power in L-Carnitine group were significantly more than ones in placebo (P<0.05.Conclusion: These findings indicate that acute oral supplementation of L-Carnitine can induce fatigue decreasing and improvement of aerobic and anaerobic performance.

  20. Over-expression in Escherichia coli, purification and reconstitution in liposomes of the third member of the OCTN sub-family: The mouse carnitine transporter OCTN3

    Energy Technology Data Exchange (ETDEWEB)

    Scalise, Mariafrancesca; Galluccio, Michele; Pochini, Lorena [Department of Cell Biology, University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (Italy); Indiveri, Cesare, E-mail: indiveri@unical.it [Department of Cell Biology, University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (Italy)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer mOCTN3 transport protein has been cloned in pET-21a(+) and over-expressed in Escherichia coli. Black-Right-Pointing-Pointer The expressed mOCTN3 has been purified to homogeneity by Ni-chelating chromatography. Black-Right-Pointing-Pointer The protein solubilised in Triton X-100 has been reconstituted in liposomes. Black-Right-Pointing-Pointer Recombinant mOCTN3 catalyses transport of carnitine by a uniport mode. -- Abstract: pET-21a(+)-mOCTN3-6His was constructed and used for over-expression in Escherichia coli Rosetta(DE3)pLysS. After IPTG induction a protein with apparent molecular mass of 53 kDa was collected in the insoluble fraction of the cell lysate and purified by Ni{sup 2+}-chelating chromatography with a yield of 2 mg/l of cell culture. The over-expressed protein was identified with mOCTN3 by anti-His antibody and reconstitution in liposomes. mOCTN3 required peculiar conditions for optimal expression and reconstitution in liposomes. The protein catalyzed a time dependent [{sup 3}H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The K{sub m} for carnitine was 36 {mu}M. [{sup 3}H]carnitine transport was inhibited by carnitine analogues and some Cys and NH{sub 2} reagents. This paper represents the first outcome in over-expressing, in active form, the third member of the OCTN sub-family, mOCTN3, in E. coli.

  1. Over-expression in Escherichia coli, purification and reconstitution in liposomes of the third member of the OCTN sub-family: The mouse carnitine transporter OCTN3

    International Nuclear Information System (INIS)

    Scalise, Mariafrancesca; Galluccio, Michele; Pochini, Lorena; Indiveri, Cesare

    2012-01-01

    Highlights: ► mOCTN3 transport protein has been cloned in pET-21a(+) and over-expressed in Escherichia coli. ► The expressed mOCTN3 has been purified to homogeneity by Ni-chelating chromatography. ► The protein solubilised in Triton X-100 has been reconstituted in liposomes. ► Recombinant mOCTN3 catalyses transport of carnitine by a uniport mode. -- Abstract: pET-21a(+)-mOCTN3-6His was constructed and used for over-expression in Escherichia coli Rosetta(DE3)pLysS. After IPTG induction a protein with apparent molecular mass of 53 kDa was collected in the insoluble fraction of the cell lysate and purified by Ni 2+ -chelating chromatography with a yield of 2 mg/l of cell culture. The over-expressed protein was identified with mOCTN3 by anti-His antibody and reconstitution in liposomes. mOCTN3 required peculiar conditions for optimal expression and reconstitution in liposomes. The protein catalyzed a time dependent [ 3 H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The K m for carnitine was 36 μM. [ 3 H]carnitine transport was inhibited by carnitine analogues and some Cys and NH 2 reagents. This paper represents the first outcome in over-expressing, in active form, the third member of the OCTN sub-family, mOCTN3, in E. coli.

  2. Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Topcu-Tarladacalisir, Yeter; Kanter, Mehmet [Trakya University, Department of Histology and Embryology, Faculty of Medicine, Edirne (Turkey); Uzal, Mustafa Cem [Trakya University, Department of Radiation Oncology, Faculty of Medicine, Edirne (Turkey)

    2009-08-15

    The present study, we hypothesized that l-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma ({gamma})-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal {gamma}-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + l-carnitine group received scrotal {gamma}-irradiation plus 200 mg/kg i.p. l-carnitine. l-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of {gamma}-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, l-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy. (orig.)

  3. Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

    International Nuclear Information System (INIS)

    Topcu-Tarladacalisir, Yeter; Kanter, Mehmet; Uzal, Mustafa Cem

    2009-01-01

    The present study, we hypothesized that l-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (γ)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal γ-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + l-carnitine group received scrotal γ-irradiation plus 200 mg/kg i.p. l-carnitine. l-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of γ-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, l-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy. (orig.)

  4. Myocardial Protective Effects of L-Carnitine on Ischemia-Reperfusion Injury in Patients With Rheumatic Valvular Heart Disease Undergoing Cardiac Surgery.

    Science.gov (United States)

    Li, Ming; Xue, Li; Sun, Haifeng; Xu, Suochun

    2016-12-01

    The authors used L-carnitine as an ingredient in cardioplegic solution during valve replacement surgery to investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury (MIRI) and its possible mechanism. Prospective, randomized study. A tertiary-care hospital. The study comprised 90 patients undergoing valve replacement under cardiopulmonary bypass. Patients were divided randomly into 3 groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (3 g/L) and experimental group 2 (6 g/L), whereas no L-carnitine was used in the control group. The remainder of the treatment was identical for all 3 groups. Serum was collected from each patient 1 hour before the surgery and at 2, 6, 24, and 72 hours after unclamping the aorta, and tissue samples were obtained before cardiac arrest and after unclamping the aorta. The postoperative levels of serum aspartate aminotransferase, creatine kinase, creatine kinase-MB isozyme, and lactic acid dehydrogenase and the apoptotic index were all lower in the 2 experimental groups than those in the control group. In addition, each of the aforementioned serum enzyme levels and the apoptotic index in all 3 groups significantly increased after unclamping the aorta compared with baseline levels taken before surgery. Bcl-2 expression was higher and Bax was lower in the 2 experimental groups compared with those of the control group after unclamping the aorta. However, there was no significant difference in all the postoperative indices between the 2 experimental groups. L-carnitine may reduce cardiopulmonary bypass-induced myocardial apoptosis through modulating the expressions of Bcl-2 and Bax, resulting in a protective effect from MIRI. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Creatine, L-carnitine, and ω3 polyunsaturated fatty acid supplementation from healthy to diseased skeletal muscle.

    Science.gov (United States)

    D'Antona, Giuseppe; Nabavi, Seyed Mohammad; Micheletti, Piero; Di Lorenzo, Arianna; Aquilani, Roberto; Nisoli, Enzo; Rondanelli, Mariangela; Daglia, Maria

    2014-01-01

    Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases.

  6. An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency.

    Science.gov (United States)

    Melek, Engin; Bulut, Fatma Derya; Atmış, Bahriye; Yılmaz, Berna Şeker; Bayazıt, Aysun Karabay; Mungan, Neslihan Önenli

    2017-02-01

    Carnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

  7. Creatine, L-Carnitine, and ω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle

    Science.gov (United States)

    D'Antona, Giuseppe; Nabavi, Seyed Mohammad; Micheletti, Piero; Aquilani, Roberto; Nisoli, Enzo; Rondanelli, Mariangela; Daglia, Maria

    2014-01-01

    Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases. PMID:25243159

  8. L-carnitine is an endogenous HDAC inhibitor selectively inhibiting cancer cell growth in vivo and in vitro.

    Science.gov (United States)

    Huang, Hongbiao; Liu, Ningning; Guo, Haiping; Liao, Siyan; Li, Xiaofen; Yang, Changshan; Liu, Shouting; Song, Wenbin; Liu, Chunjiao; Guan, Lixia; Li, Bing; Xu, Li; Zhang, Change; Wang, Xuejun; Dou, Q Ping; Liu, Jinbao

    2012-01-01

    L-carnitine (LC) is generally believed to transport long-chain acyl groups from fatty acids into the mitochondrial matrix for ATP generation via the citric acid cycle. Based on Warburg's theory that most cancer cells mainly depend on glycolysis for ATP generation, we hypothesize that, LC treatment would lead to disturbance of cellular metabolism and cytotoxicity in cancer cells. In this study, Human hepatoma HepG2, SMMC-7721 cell lines, primary cultured thymocytes and mice bearing HepG2 tumor were used. ATP content was detected by HPLC assay. Cell cycle, cell death and cell viability were assayed by flow cytometry and MTS respectively. Gene, mRNA expression and protein level were detected by gene microarray, Real-time PCR and Western blot respectively. HDAC activities and histone acetylation were detected both in test tube and in cultured cells. A molecular docking study was carried out with CDOCKER protocol of Discovery Studio 2.0 to predict the molecular interaction between L-carnitine and HDAC. Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro; (2) LC treatment selectively induces the expression of p21(cip1) gene, mRNA and protein in cancer cells but not p27(kip1); (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells; (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro; (6) LC treatment induces accumulation of acetylated histones in chromatin associated with the p21(cip1) gene but not p27(kip1) detected by ChIP assay. These data support that LC, besides transporting acyl group, works as an endogenous HDAC inhibitor in the cell, which would be of physiological and pathological importance.

  9. Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid.

    Science.gov (United States)

    Ando, Masazumi; Amayasu, Hideaki; Itai, Takahiro; Yoshida, Hisahiro

    2017-01-01

    Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. The blood ammonia level was positively correlated with the serum glutamate concentration ( r  = 0.44, p  < 0.01) but negatively correlated with glutamine ( r  = -0.41, p  = 0.01), citrulline ( r  = -0.42, p  = 0.01), and glycine concentrations ( r  = -0.54, p  < 0.01). It was also revealed that the concomitant administration of the mood stabilizers ( p  = 0.04) risperidone ( p  = 0.03) and blonanserin ( p  < 0.01) was positively associated with the elevation of the blood ammonia level. We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.

  10. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

    Directory of Open Access Journals (Sweden)

    Murat Caloglu

    2012-01-01

    Full Text Available Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6, Group 2: irradiation alone (RT, n = 8, Group 3: amifostine plus irradiation (AMI+RT, n = 8, and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8. The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg or amifostine (200 mg/kg was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. Results: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009 compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003 and LC+RT group (P = 0.029 compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009. There was not any significant difference between the LC+RT and RT group. Conclusions: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

  11. Effect of L-carnitine and pyruvate on equine sperm maintained at 5 ºC and 15 ºC during 24 h: preliminary results

    Directory of Open Access Journals (Sweden)

    Avila G

    2016-12-01

    Full Text Available The aim of this study was to evaluate if the addition of L-carnitine and pyruvate to two semen transport extenders (Kenney and Kenney modified by Tyrodes is able to maintain sperm parameters for 24 h at 5 ºC and 15 ºC. Semen was obtained from 3 stallions (n=3; r=2 and at time 0 and after 24 h of cooling, the following parameters evaluated: total and progressive motility (CASA, viability and acrosome status (FITC-PNA-PI, membrane function (HOS, and DNA with Toluidine Blue stain (TB and the Sperm Chromatin Dispersion assay (SCD. Each temperature was individually analyzed using a factorial design with a 5% significance level. No interactions were observed. For the moment, the Kenney extender with the addition of L-carnitine and pyruvate showed the best results for maintaining most sperm parameters for 24 h at both 5 ºC and 15 ºC.

  12. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    John T Kissel

    Full Text Available BACKGROUND: Multiple lines of evidence have suggested that valproic acid (VPA might benefit patients with spinal muscular atrophy (SMA. The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. METHODS: This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend, timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP, handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. RESULTS: Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. CONCLUSIONS: This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.

  13. Simple determination of betaine, l-carnitine and choline in human urine using self-packed column and column-switching ion chromatography with nonsuppressed conductivity detection.

    Science.gov (United States)

    Wei, Dan; Zhu, Yan; Guo, Ming

    2018-02-01

    A sequential online extraction, clean-up and separation system for the determination of betaine, l-carnitine and choline in human urine using column-switching ion chromatography with nonsuppressed conductivity detection was developed in this work. A self-packed pretreatment column (50 × 4.6 mm, i.d.) was used for the extraction and clean-up of betaine, l-carnitine and choline. The separation was achieved using self-packed cationic exchange column (150 × 4.6 mm, i.d.), followed by nonsuppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in the range of 0.60-100 μg mL -1 for betaine, 0.75-100 μg mL -1 for l-carnitine and 0.50-100 μg mL -1 for choline, with all correlation coefficients (R 2 ) >0.99 in urine. The limits of detection were 0.15 μg mL -1 for betaine, 0.20 μg mL -1 for l-carnitine and 0.09 μg mL -1 for choline. The intra- and inter-day accuracy and precision for all quality controls were within ±10.32 and ±9.05%, respectively. Satisfactory recovery was observed between 92.8 and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method showed good agreement with the measurement reported previously. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Determination of betaine, l-carnitine, and choline in human urine using a self-packed column and column-switching ion chromatography with nonsuppressed conductivity detection.

    Science.gov (United States)

    Wei, Dan; Liu, Junwei; Guo, Ming; Zhu, Yan

    2017-11-01

    A simple method for the determination of betaine, l-carnitine, and choline in human urine was developed based on column-switching ion chromatography coupled with nonsuppressed conductivity detection by using a self-packed column. A pretreatment column (50 mm × 4.6 mm, id) packed with poly(glycidyl methacrylate-divinylbenzene) microspheres was used for the extraction and cleanup of analytes. Chromatographic separation was achieved within 10 min on a cationic exchange column (150 mm × 4.6 mm, id) using maleic anhydride modified poly(glycidyl methacrylate-divinylbenzene) as the particles for packing. The detection was performed by ion chromatography with nonsuppressed conductivity detection. Parameters including column-switching time, eluent type, flow rates of eluent, and interfering effects were optimized. Linearity (r 2 ≥ 0.99) was obtained for the concentration range of 0.50-100, 0.75-100, and 0.25-100 μg/mL for betaine, l-carnitine, and choline, respectively. Detection limits were 0.12, 0.20, and 0.05 μg/mL for betaine, l-carnitine, and choline, respectively. The intra- and interday accuracy and precision for all quality controls were within ±10.11%. Satisfactory recovery was observed between 92.5 and 105.0%. The validated method was successfully applied for the determination of betaine, l-carnitine, and choline in urine samples from healthy people. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-{sup 11}C]propionyl L-carnitine for pharmacokinetic studies

    Energy Technology Data Exchange (ETDEWEB)

    Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K. [Hammersmith Hospital, London (United Kingdom). MRC Cyclotron Unit

    1997-07-30

    Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t{sub 1/2} = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [{sup 11}C]propionyl chloride as labelling agent via {sup 11}C-carboxylation of ethylmagnesium bromide with cyclotron-produced [{sup 11}C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [{sup 11}C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [{sup 11}C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [{sup 11}C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [{sup 11}C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [{sup 11}C]carbon dioxide and hydrolysis. NCA [{sup 11}C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [{sup 11}C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [{sup 11}C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [{sup 11}C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [{sup 11}C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [{sup 11}C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author).

  16. Effects of telmisartan in combined with L-carnitine on the oxidative stress and micro-inflammation status in peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Jin-Xiu Cheng

    2016-06-01

    Full Text Available Objective: To explore the effects of telmisartan in combined with L-carnitine on the oxidative stress and micro-inflammation status in peritoneal dialysis (PD patients. Methods: A total of 80 patients with chronic renal failure (CRF who were admitted in our hospital from November, 2011 to January, 2014 for PD were included in the study and randomized into the treatment group and the control group. The patients in the two groups were routinely performed with PD. The patients in the treatment group were given L-carnitine oral liquid, 10 mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were given L-carnitine oral liquid, 10 mL/time, 3 times a day. The patients in the two groups were treated for 24 weeks continuously. A volume of 5 mL morning fasting venous blood before and after treatment was extracted, and centrifuged for serum. The levels of hs-CRP, IL-6, IL-8, TNF-α, MDA, and GSH-Px were determined. Results: After treatment, the levels of hs-CRP, IL-6, IL-8, and TNF-α were reduced, and the reduced degree in the treatment group was significantly superior to that in the control group. After treatment, MDA was reduced, GSH-Px was elevated, and the reduced degree and elevated degree in the treatment group were significantly superior to those in the control group. Conclusions: Telmisartan in combined with L-carnitine can probably become an ideal therapeutic measure for inhibiting the micro-inflammation state and oxidative stress reaction in PD patients, thus reducing the risk of cardiovascular events, which can provide an evidence for the clinical application in the future.

  17. A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

    Science.gov (United States)

    Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

    2013-10-07

    There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

  18. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

    Science.gov (United States)

    Blancquaert, Laura; Baguet, Audrey; Bex, Tine; Volkaert, Anneke; Everaert, Inge; Delanghe, Joris; Petrovic, Mirko; Vervaet, Chris; De Henauw, Stefaan; Constantin-Teodosiu, Dumitru; Greenhaff, Paul; Derave, Wim

    2018-04-01

    Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (Pvegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

  19. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  20. Effect of Magnetic Field Exposure on Testicular function and Prophylactic Role of Coenzyme Q10 and L-Carnitine in Mice

    International Nuclear Information System (INIS)

    Ramadan, L.A.; Abd-Allah, A.R.A.; Aly, H.A.A.

    2004-01-01

    The protective effect of L-carnitine or Co enzyme Q 10 (Co Q 10) against high magnetic field (20 mt) induced testicular toxicity in mice was evaluated. Animals were injected with L-carnitine (200 mg/kg i.p.) or Co Q 10(200 mg/kg per o.s.) 1 hr before exposure to fractionated doses (1/2 h/day, 3 times per week for 2 weeks) or acute dose (3 hr) of magnetic field. Total sperm count motility, daily sperm production and testicular LDH-X activity as well as histopathological examination were investigated. Exposure of mice to fractionated doses of magnetic field caused a significant decrease in sperm count, motility, daily sperm production and LDH-X activity,which were more pronounced than those of acute dose. Moreover,marked testicular histopathological changes were observed after exposure to fractionated doses of magnetic field. Pretreatment of mice with L-carnitine or Co Q 10 1 hr before exposure to the magnetic field caused a significant recovery of testicular damage induced by high magnetic field (20 mT)

  1. Flux control analysis of mitochondrial oxidative phosphorylation in rat skeletal muscle: pyruvate and palmitoyl-carnitine as substrates give different control patterns

    DEFF Research Database (Denmark)

    Fritzen, Anette J; Grunnet, Niels; Quistorff, Bjørn

    2007-01-01

    was associated with the ADP-generating system, i.e., 0.58 +/- 0.05 with pyruvate, but significantly lower, 0.40 +/- 0.05, with palmitoyl-carnitine as substrate. The flux control coefficients of complex I, III and IV, the ATP synthase, the ATP/ADP carrier and the P(i) carrier were 0.070 +/- 0.03, 0.083 +/- 0.......04, 0.054 +/- 0.01, 0.11 +/- 0.03, 0.090 +/- 0.03 and 0.026 +/- 0.01, respectively, with pyruvate as substrate. With palmitoyl-carnitine all control coefficients were significantly different, except for the P(i) carrier (i.e., 0.024 +/- 0.001, 0.036 +/- 0.01, 0.052 +/- 0.02, 0.020 +/- 0.002, 0.034 +/- 0.......02 and 0.012 +/- 0.002, respectively), probably caused by the shift from NADH to FADH(2) oxidation. The sum of flux control coefficients was not significantly different from unity with pyruvate, while only 0.58 with palmitoyl-carnitine, indicating significant control contributions from the enzymes involved...

  2. Immunomodulatory effects of L-carnitine and q10 in mouse spleen exposed to low-frequency high-intensity magnetic field

    International Nuclear Information System (INIS)

    Arafa, Hossam M.M.; Abd-Allah, Adel R.A.; El-Mahdy, Mohamad A.; Ramadan, Laila A.; Hamada, Farid M.A.

    2003-01-01

    In the current study, we have investigated the bioeffects of repeated exposure to low-frequency (50 Hz) high-intensity (20 mT; 200 G) electromagnetic field (EMF) on some immune parameters in mice. The animals were exposed to EMF daily for 30 min three times per week for 2 weeks. We also studied the possible immunomodulatory effects of two anti-radical substances known to have non-specific immunostimulant effects namely, L-carnitine (200 mg/kg body weight i.p.) and Q10 (200 mg/kg body weight, p.o.). Both drugs were given 1 h prior to each EMF exposure. Immune endpoints included total body weight, spleen/body weight ratio, splenocytes viability, total and differential white blood cell (WBCs; lymphocytes, monocytes, neutrophils) counts, as well as the lymphocyte proliferation induced by the mitogens; phytohaemagglutinin (PHA), concanavalin-A (Con-A) and lipoploysaccharide (LPS). Magnetic field decreased splenocyte viability, WBCs count, as well as mitogens-induced lymphocyte proliferation. L-carnitine, but not Q10 could ameliorate the adverse effects of EMF on the vast majority of the immune parameters tested, suggesting a possible immunoprotective role of L-carnitine under the current experimental conditions

  3. Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

    Science.gov (United States)

    Ji, L L; Miller, R H; Nagle, F J; Lardy, H A; Stratman, F W

    1987-08-01

    The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

  4. L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/β-catenin and PKA pathway.

    Science.gov (United States)

    Fathi, Ezzatollah; Farahzadi, Raheleh; Charoudeh, Hojjatollah Nozad

    2017-03-01

    The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/β-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR. ELISA was conducted to assess the expression of cyclic adenosine monophosphate (cAMP) and PKA. The expression of β-catenin, reduced dickkopf1 (DKK1), low-density lipoprotein receptor-related protein 5 (LRP5), Wnt1, and Wnt3a genes as Wnt/β-catenin signaling members were used to detect the Wnt/β-catenin pathway. It was observed that LC could promote neurogenesis in ADSCs as well as expression of some neurogenic markers. Moreover, LC causes to increase the cAMP levels and PKA activity. Treatment of ADSCs with H-89 (dihydrochloride hydrate) as PKA inhibitor significantly inhibited the promotion of neurogenic markers, indicating that the PKA signaling pathway could be involved in neurogenesis induction. Analyses of real-time PCR data showed that the mRNA expressions of β-catenin, DKK1, LRP5c-myc, Wnt1, and Wnt3a were increased in the presence of LC. Therefore, the present study showed that LC promotes ADSCs neurogenesis and the LC-induced neurogenic markers could be due to both the PKA and Wnt/β-catenin signaling pathway. Impact statement Neural tissue has long been believed as incapable of regeneration and the identification of cell types and factors capable of neuronal differentiation has generated intense interest. Mesenchymal stem cells (MSCs) are considered as potential targets for stem cell-based therapy. L-carnitin (LC) as an antioxidant may have neuroprotective effects in

  5. NR4A nuclear receptors mediate carnitine palmitoyltransferase 1A gene expression by the rexinoid HX600

    Energy Technology Data Exchange (ETDEWEB)

    Ishizawa, Michiyasu [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan); Kagechika, Hiroyuki [Graduate School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Makishima, Makoto, E-mail: makishima.makoto@nihon-u.ac.jp [Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610 (Japan)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer The function of RXR heterodimers with NR4 receptors remains unknown. Black-Right-Pointing-Pointer The RXR ligand HX600 induces expression of carnitine palmitoyltransferase 1A (CPT1A). Black-Right-Pointing-Pointer HX600-induced CPT1A expression is mediated by the NR4 receptors, Nur77 and NURR1. Black-Right-Pointing-Pointer CPT1A induction by HX600 is not mediated by de novo protein synthesis. Black-Right-Pointing-Pointer CPT1A could be a target of the Nur77-RXR and NURR1-RXR heterodimers. -- Abstract: Retinoid X receptors (RXRs) are members of the nuclear receptor superfamily and can be activated by 9-cis retinoic acid (9CRA). RXRs form homodimers and heterodimers with other nuclear receptors such as the retinoic acid receptor and NR4 subfamily nuclear receptors, Nur77 and NURR1. Potential physiological roles of the Nur77-RXR and NURR1-RXR heterodimers have not been elucidated. In this study, we identified a gene regulated by these heterodimers utilizing HX600, a selective RXR agonist for Nur77-RXR and NURR1-RXR. While 9CRA induced many genes, including RAR-target genes, HX600 effectively induced only carnitine palmitoyltransferase 1A (CPT1A) in human teratocarcinoma NT2/D1 cells, which express RXR{alpha}, Nur77 and NURR1. HX600 also increased CPT1A expression in human embryonic kidney (HEK) 293 cells and hepatocyte-derived HepG2 cells. Although HX600 induced CPT1A less effectively than 9CRA, overexpression of Nur77 or NURR1 increased the HX600 response to levels similar to 9CRA in NT2/D1 and HEK293 cells. A dominant-negative form of Nur77 or NURR1 repressed the induction of CPT1A by HX600. A protein synthesis inhibitor did not alter HX600-dependent CPT1A induction. Thus, the rexinoid HX600 directly induces expression of CPT1A through a Nur77 or NURR1-mediated mechanism. CPT1A, a gene involved in fatty acid {beta}-oxidation, could be a target of RXR-NR4 receptor heterodimers.

  6. Short communication: the pharmacological peroxisome proliferator-activated receptor α agonist WY-14,643 increases expression of novel organic cation transporter 2 and carnitine uptake in bovine kidney cells.

    Science.gov (United States)

    Zhou, X; Wen, G; Ringseis, R; Eder, K

    2014-01-01

    Recent studies in rodents demonstrated that peroxisome proliferator-activated receptor α (PPARα), a central regulator of energy homeostasis, is an important transcriptional regulator of the gene encoding the carnitine transporter novel organic cation transporter 2 (OCTN2). Less is known with regard to the regulation of OCTN2 by PPARα and its role for carnitine transport in cattle, even though PPARα activation physiologically occurs in the liver of high-producing cows during early lactation. To explore the role of PPARα for OCTN2 expression and carnitine transport in cattle, we studied the effect of the PPARα activator WY-14,643 on the expression of OCTN2 in the presence and absence of PPARα antagonists and on OCTN2-mediated carnitine transport in the Madin-Darby bovine kidney (MDBK) cell line. The results show that WY-14,643 increases mRNA and protein levels of OCTN2, whereas co-treatment of MDBK cells with WY-14,643 and the PPARα antagonist GW6471 blocks the WY-14,643-induced increase in mRNA and protein levels of OCTN2 in bovine cells. In addition, treatment of MDBK cells with WY-14,643 stimulates specifically Na(+)-dependent carnitine uptake in MDBK cells, which is likely the consequence of the increased carnitine transport capacity of cells due to the elevated expression of OCTN2. In conclusion, our results indicate that OCTN2 expression and carnitine transport in cattle, as in rodents, are regulated by PPARα. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial

    Science.gov (United States)

    Badrasawi, M; Shahar, Suzana; Zahara, AM; Nor Fadilah, R; Singh, Devinder Kaur Ajit

    2016-01-01

    Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. Methodology This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. Results The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults. PMID:27895474

  8. Effect of different levels of vitamin C and L-carnitine on performance and some blood and immune parameters of broilers under heat stress.

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    Saeed Mirzapor Sarab

    2016-08-01

    Full Text Available Introduction: High Environmental temperature during summer months which leading to heat stress, is of great concern in all types of poultry production. Feed consumption, growth rate, hatchability, mortality, and other important traits governing the prosperity of the industry are adversely affected by severe heat stress. Literature suggests that the advantages of dietary L-carnitine and ascorbic acid have been particularly apparent under heat stress (8. L- carnitine is a zwitterionic compound synthesized in vivo from lysine and methonine, and is essential for the transport of long – chain fatty acid across the inner mitochondria membrane for β – oxidation and remove toxic accumulations of fatty acids from mitochondria (18. Vitamin C is an effective antioxidant, which is essential for collagen synthesis, helps to maintain various enzymes in their required reduced form, and participates in the biosynthesis of carnitine, norepinephrine and certain neuroendocrine peptides (11. Invertebrates, insects, most fishes, some birds, guinea-pigs, bats and primates are not able to synthesize ascorbic acid. Thus, these animals must depend upon a dietary supply of this vitamin C. In poultry, ascorbic acid has been demonstrated to be essential for growth (25. Materials and Methods: In this study, 396 of Ross 308 broiler chicks in a completely randomized design with 3 × 3 factorial arrangement with 4 replicates of 11 chicks in each replicate were used for 42 days. Treatments were 3 levels of vitamin C (0, 250 and 500 mg/ kg and 3 levels of L-carnitine (0, 50 and 100 mg kg. In the first 3 weeks of breeding, broilers were under normal temperature and heat stress was done from the beginning of forth week. Feed and water were provided ad-libitum. Performance parameters were recorded weekly. The 0.5 mL suspension of 5% SRBC was injected at 28 and 35 days of age in one bird of each pen. To determine the antibody titer, blood was collected 1 week after each

  9. Aplicações clínicas da suplementação de L-carnitina Clinical uses of L-carnitine supplementation

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    Christianne de Faria Coelho

    2005-10-01

    Full Text Available A carnitina, uma amina quaternária (3-hidroxi-4-N-trimetilamino-butirato, é sintetizada no organismo (fígado, rins e cérebro a partir de dois aminoácidos essenciais: lisina e metionina, exigindo para sua síntese a presença de ferro, ácido ascórbico, niacina e vitamina B6. Tem função fundamental na geração de energia pela célula, pois age nas reações transferidoras de ácidos graxos livres do citosol para mitocôndrias, facilitando sua oxidação e geração de adenosina Trifosfato. A concentração orgânica de carnitina é resultado de processos metabólicos - como ingestão, biossíntese, transporte dentro e fora dos tecidos e excreção - que, quando alterados em função de diversas doenças, levam a um estado carencial de carnitina com prejuízos relacionados ao metabolismo de lipídeos. A suplementação de L-carnitina pode aumentar o fluxo sangüíneo aos músculos devido também ao seu efeito vasodilatador e antioxidante, reduzindo algumas complicações de doenças isquêmicas, como a doença arterial coronariana, e as conseqüências da neuropatia diabética. Por esse motivo, o objetivo do presente trabalho foi descrever possíveis benefícios da suplementação de carnitina nos indivíduos com necessidades especiais e susceptíveis a carências de carnitina, como os portadores de doenças renais, neuropatia diabética, síndrome da imunodefeciência adquirida e doenças cardiovasculares.Carnitine, a quaternary amine (3-hidroxy-4-n-trimethylaminobutyrate is synthesized in the body (liver, kidney and brain from lysine and methionine, two essential amino acids, in the presence of iron, ascorbate, niacin and vitamin B6. Carnitine plays a central role in the cellular energy metabolism because it transports long-chain fatty acids from the cytosol to the mitochondria for oxidation and adenosine 5'-triphosphate generation. The organic concentration of carnitine is a result of several metabolic pathways such as ingestion

  10. Effect of L-Carnitine on Skeletal Muscle Lipids and Oxidative Stress in Rats Fed High-Fructose Diet

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    Panchamoorthy Rajasekar

    2007-01-01

    Full Text Available There is evidence that high-fructose diet induces insulin resistance, alterations in lipid metabolism, and oxidative stress in rat tissues. The purpose of this study was to evaluate the effect of L-carnitine (CAR on lipid accumulation and peroxidative damage in skeletal muscle of rats fed high-fructose diet. Fructose-fed animals (60 g/100 g diet displayed decreased glucose/insulin (G/I ratio and insulin sensitivity index (ISI0,120 indicating the development of insulin resistance. Rats showed alterations in the levels of triglycerides, free fatty acids, cholesterol, and phospholipids in skeletal muscle. The condition was associated with oxidative stress as evidenced by the accumulation of lipid peroxidation products, protein carbonyls, and aldehydes along with depletion of both enzymic and nonenzymic antioxidants. Simultaneous intraperitoneal administration of CAR (300 mg/kg/day to fructose-fed rats alleviated the effects of fructose. These rats showed near-normal levels of the parameters studied. The effects of CAR in this model suggest that CAR supplementation may have some benefits in patients suffering from insulin resistance.

  11. BIOCHEMICAL PARAMETERS OF LIPID METABOLISM IN ANIMALS AFFECTED BY HEAVY METAL SALTS AND TREATED WITH CARNITINE CHLORIDE AND SODIUM ALGINATE

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    I. R. Bekus

    2017-02-01

    Full Text Available Background. Lipid metabolism disorders in the organism affected by environmental pollutants, including poisoning with cadmium and lead salts are of topical matter nowadays. Objective. The study was aimed to examine biochemical features of lipid metabolism in rats subjected to toxic damage by lead and cadmium salts and treated with carnitine chloride and Algigel. Methods. Experiments were carried out on white mature outbred male rats weighing 180-200 g. To cause the toxic damage the animals were administered with aqueous solution of cadmium chloride and lead acetate daily for the period of 30 days using intra-gastric lavage. The indices of lipid metabolism were detected by biochemical methods. Results. In animals treated with cadmium chloride and lead acetate the following changes were observed: HDL-cholesterol concentrations significantly decreased, resulting in 87% of the levels in the intact animals on the third day, 84% on the fifth and 80% on the seventh day. Conversely, concentrations of HDL-cholesterol and VLDL-cholesterol significantly increased during the experiment. Respectively, the ratios for HDL-cholesterol are 240%, 352%, and 388%; and for VLDL-cholesterol 108%, 116%, and 132%. Conclusions. Lipids profile of the rats displayed changes in the levels of cholesterol, triglycerides and lipoproteins of low, high and very low density.

  12. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic Acid and saw palmetto extract.

    Science.gov (United States)

    Chittur, Sridar; Parr, Brian; Marcovici, Geno

    2011-01-01

    Chronic inflammation of the hair follicle (HF) is considered a contributing factor in the pathogenesis of androgenetic alopecia (AGA). Previously, we clinically tested liposterolic extract of Serenoa repens (LSESr) and its glycoside, β-sitosterol, in subjects with AGA and showed a highly positive response to treatment. In this study, we sought to determine whether blockade of inflammation using a composition containing LSESr as well as two anti-inflammatory agents (carnitine and thioctic acid) could alter the expression of molecular markers of inflammation in a well-established in vitro system. Using a well-validated assay representative of HF keratinocytes, specifically, stimulation of cultured human keratinocyte cells in vitro, we measured changes in gene expression of a spectrum of well-known inflammatory markers. Lipopolysaccharide (LPS) provided an inflammatory stimulus. In particular, we found that the composition effectively suppressed LPS-activated gene expression of chemokines, including CCL17, CXCL6 and LTB(4) associated with pathways involved in inflammation and apoptosis. Our data support the hypothesis that the test compound exhibits anti-inflammatory characteristics in a well-established in vitro assay representing HF keratinocyte gene expression. These findings suggest that 5-alpha reductase inhibitors combined with blockade of inflammatory processes could represent a novel two-pronged approach in the treatment of AGA with improved efficacy over current modalities.

  13. Inhibition of Inflammatory Gene Expression in Keratinocytes Using a Composition Containing Carnitine, Thioctic Acid and Saw Palmetto Extract

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    Sridar Chittur

    2011-01-01

    Full Text Available Chronic inflammation of the hair follicle (HF is considered a contributing factor in the pathogenesis of androgenetic alopecia (AGA. Previously, we clinically tested liposterolic extract of Serenoa repens (LSESr and its glycoside, β-sitosterol, in subjects with AGA and showed a highly positive response to treatment. In this study, we sought to determine whether blockade of inflammation using a composition containing LSESr as well as two anti-inflammatory agents (carnitine and thioctic acid could alter the expression of molecular markers of inflammation in a well-established in vitro system. Using a well-validated assay representative of HF keratinocytes, specifically, stimulation of cultured human keratinocyte cells in vitro, we measured changes in gene expression of a spectrum of well-known inflammatory markers. Lipopolysaccharide (LPS provided an inflammatory stimulus. In particular, we found that the composition effectively suppressed LPS-activated gene expression of chemokines, including CCL17, CXCL6 and LTB(4 associated with pathways involved in inflammation and apoptosis. Our data support the hypothesis that the test compound exhibits anti-inflammatory characteristics in a well-established in vitro assay representing HF keratinocyte gene expression. These findings suggest that 5-alpha reductase inhibitors combined with blockade of inflammatory processes could represent a novel two-pronged approach in the treatment of AGA with improved efficacy over current modalities.

  14. Children at risk of diabetes type 1. Treatment with acetyl-L-carnitine plus nicotinamide - case reports.

    Science.gov (United States)

    Fernandez, Ivana Cristina; Del Carmen Camberos, María; Passicot, Gisel Anabel; Martucci, Lucía Camila; Cresto, Juan Carlos

    2013-01-01

    Abstract Objectives: The aim was to evaluate the treatment with acetyl-L-carnitine (50 mg/kg/day) and nicotinamide (25 mg/kg/day) in children at risk of type 1 diabetes. This treatment was effective and harmless in experimental type 1 diabetes in mice. Nine out of seventy healthy participants of the type 1 diabetes risk study were treated. They were typified for diabetes with HLA-DQB1 and positive autoantibodies. Children with a first peak of insulin response ≤48 µU were randomly distributed in control and treated patients. Children evolution was followed with an intravenous glucose tolerance test. Control children were treated when was another risk parameter was added. During their evolution all children were treated. Treatment periods differ (range: 120-16 months) because children began treatment at different times. During the treatment 4 patients recovered their parameters and the medication was suspended; 2 patients continued the treatment with favorable evolution. Two children evolved slowly with normal growth and development. One girl became diabetic because she was treated late. In children at risk, this treatment delays the development or remits the evolution of type 1 diabetes.

  15. HDAC inhibitor L-carnitine and proteasome inhibitor bortezomib synergistically exert anti-tumor activity in vitro and in vivo.

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    Hongbiao Huang

    Full Text Available Combinations of proteasome inhibitors and histone deacetylases (HDAC inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21(cip1 gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like activity assay. Here we report that (i the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii the combination also synergistically inhibits tumor growth in vivo; (iii two major pathways are involved in the synergistical effects of the combinational treatment: increased p21(cip1 expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials.

  16. Solving manufacturing problems for L-carnitine-L-tartrate to improve the likelihood of successful product scale-up

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    Badawi Aliaa A.

    2017-12-01

    Full Text Available L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a problem in tablet production due to pronounced adhesion of tablets to punches. A 33 full factorial design was adopted to suggest a tablet formulation. Three adsorbents were suggested (Aerosil 200, Aerosil R972, talc to reduce stickiness at three concentrations (1, 3 and 5 %, and three fillers (mannitol, Avicel PH 101, Dibasic calcium phosphate were chosen to prepare 27 formulations. Micromeritic properties of formulations were studied, and tablets were prepared by wet granulation. Absence of picking, sticking or capping, recording of sufficient hardness, acceptable friability and tablet ejection force indicated formulation success. The resulting formulation prepared using Avicel PH 101 and 1 % Aerosil 200 was submitted to further investigation in order to choose the most suitable compression conditions using a 33 full factorial design. Variables included compression force, tableting rate and magnesium stearate (lubricant concentration. The formulation prepared at compression force of 25 kN, using 2 % magnesium stearate, at a production rate of 30 tablets/ minute, was found to be the most appropriate scale up candidate.

  17. L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells

    International Nuclear Information System (INIS)

    He Mindi; Xu Shangcheng; Lu Yonghui; Li Li; Zhong Min; Zhang Yanwen; Wang Yuan; Li Min; Yang Ju; Zhang Guangbin; Yu Zhengping; Zhou Zhou

    2011-01-01

    Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl 2 ) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl 2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ m ), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.

  18. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

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    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  19. Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

    Science.gov (United States)

    Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

    2014-12-15

    The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. The Effect of L-Carnitine, Hypotaurine, and Taurine Supplementation on the Quality of Cryopreserved Chicken Semen.

    Science.gov (United States)

    Partyka, Agnieszka; Rodak, Olga; Bajzert, Joanna; Kochan, Joanna; Niżański, Wojciech

    2017-01-01

    The objective of this study was to investigate the effect of L-carnitine (LC), hypotaurine (HT), and taurine (T) on the quality of frozen-thawed chicken semen. Pooled semen samples were divided into seven aliquots (control, 1 mM LC, 5 mM LC, 1 mM HT, 10 mM HT, 1 mM T, and 10 mM T) and subjected to cryopreservation. Postthaw sperm motility was determined by IVOS system and sperm characteristics were assessed with fluorochromes and flow cytometry. The highest sperm motility and the highest percentage of viable sperm were in the HT1 group ( P < 0.01 and P < 0.05) following cryopreservation. After thawing, we observed a higher percentage of sperm without apoptosis and membrane reorganization changes in the LC1 and T1 group when compared to the control ( P < 0.05). There was a higher percentage of live sperm without lipid peroxidation (LPO) in all treatments ( P < 0.01; P < 0.05), when compared to the control group. The percentage of sperm with high mitochondrial potential significantly increased with LC1, T1, and T10 ( P < 0.05). Supplementation of the diluent with LC1, LC5, and T1 significantly ( P < 0.05) reduced DNA susceptibility to fragmentation, compared to the control and HT1 groups. These results indicate that the addition of examined antioxidants improves the quality of cryopreserved chicken semen.

  1. Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males

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    Orem Ihsan

    2009-04-01

    Full Text Available Abstract Background Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects. Methods In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 ± 3.6 years participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL, in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP and mean values (MP of sprint power output and percent decrement of power (DEC were determined per bout and standardized relative to body masss. Heart rate (HR and blood lactate (LAC were measured prior to, during and following the five sprint bouts. Results Significant main effects (p Conclusion These findings indicate that short-term oral supplementation of GPLC can enhance peak power production in resistance trained males with significantly less LAC accumulation.

  2. Oxidative stress in response to aerobic and anaerobic power testing: influence of exercise training and carnitine supplementation.

    Science.gov (United States)

    Bloomer, Richard J; Smith, Webb A

    2009-01-01

    The purpose of this study is to compare the oxidative stress response to aerobic and anaerobic power testing, and to determine the impact of exercise training with or without glycine propionyl-L-carnitine (GPLC) in attenuating the oxidative stress response. Thirty-two subjects were assigned (double blind) to placebo, GPLC-1 (1g PLC/d), GPLC-3 (3g PLC/d) for 8 weeks, plus aerobic exercise. Aerobic (graded exercise test: GXT) and anaerobic (Wingate cycle) power tests were performed before and following the intervention. Blood was taken before and immediately following exercise tests and analyzed for malondialdehyde (MDA), hydrogen peroxide (H2O2), and xanthine oxidase activity (XO). No interaction effects were noted. MDA was minimally effected by exercise but lower at rest for both GPLC groups following the intervention (p = 0.044). A time main effect was noted for H2O2 (p = 0.05) and XO (p = 0.003), with values increasing from pre- to postexercise. Both aerobic and anaerobic power testing increase oxidative stress to a similar extent. Exercise training plus GPLC can decrease resting MDA, but it has little impact on exercise-induced oxidative stress biomarkers.

  3. Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.

    Science.gov (United States)

    Smits, Loek P; Kootte, Ruud S; Levin, Evgeni; Prodan, Andrei; Fuentes, Susana; Zoetendal, Erwin G; Wang, Zeneng; Levison, Bruce S; Cleophas, Maartje C P; Kemper, E Marleen; Dallinga-Thie, Geesje M; Groen, Albert K; Joosten, Leo A B; Netea, Mihai G; Stroes, Erik S G; de Vos, Willem M; Hazen, Stanley L; Nieuwdorp, Max

    2018-03-26

    Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d 6 -choline and d 3 -carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18 F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. URL: http://www.trialregister.nl. Unique identifier: NTR 4338. © 2018 The Authors. Published on

  4. L-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC).

    Science.gov (United States)

    Abd-Allah, Adel R A; Al-Majed, Abdulhakeem A; Al-Yahya, Abdulaziz A; Fouda, Soliman I; Al-Shabana, Othman A

    2005-07-01

    Carboplatin (CP), a second generation platinum compound, is effective against various types of cancers, producing less nephrotoxicity and ototoxicity but more myelotoxicity than cisplatinum. CP-myelosuppression is the rate-limiting step of its clinical use. Prevention of CP-myelosuppression is a major target in the field of chemotherapy. Therefore, the present study investigates the use of L-carnitine (LCR)-an antioxidant, cardioprotective, neuroprotective, and immunostimulant nontoxic natural compound-to protect against CP-induced myelosuppression. The viability of BMC was studied using a trypan blue exclusion technique following incubation with CP and/or LCR as a function of time and concentration. Apoptosis was tested for by detecting the amount of DNA fragmentation and the visualization of DNA ladders upon gel electrophoresis. Bone marrow progenitor cell function was examined by colony forming unit assay. Cellular contents of glutathione (GSH) and malondialdehyde (MDA) were also estimated. Results revealed that LC50 of CP is 4.7 mM and the highest safe concentration of LCR is 5 mM. Co-exposure of LCR+CP rescued BMC viability by 37% compared to the CP-treated cultures. The LCR halts CP-induced apoptosis and it significantly improves the function of the bone marrow progenitors by increasing the number of colony-forming units as a response to granulocyte/macrophage colony stimulating factors. Finally, LCR restores CP-induced GSH depletion and prevents MDA elevation in BMC. In summary, the results suggest that LCR is able to protect against CP-induced myelosuppression, which suggests its use as an adjuvant therapy. This finding merits further investigation into the mechanism(s) of such protection as well as its interaction with CP antitumor activity.

  5. L-Carnitine in rooster semen cryopreservation: Flow cytometric, biochemical and motion findings for frozen-thawed sperm.

    Science.gov (United States)

    Fattah, A; Sharafi, M; Masoudi, R; Shahverdi, A; Esmaeili, V; Najafi, A

    2017-02-01

    Rooster semen cryopreservation is not efficient for artificial insemination in breeder flocks. L-Carnitine (LC) has been evaluated for effectiveness in cryopreservation media on the characteristics of rooster sperm after freeze-thawing. Motility characteristics, membrane functionality, abnormal morphology, apoptotic like changes, mitochondria activity and lipid peroxidation of rooster sperms were assessed after freeze-thawing with different concentrations of LC in Beltsville medium. Semen samples were collected from 12 roosters, twice a week, and diluted in the extenders that contained different concentrations of LC. Supplementation of Beltsevile with 1 and 2 mM LC was found to result in higher total motility (68.2± 1.7% and 69.1± 1.7%, respectively), progressive motility (28.4± 1.6%, 29.8± 1.6%), membrane functionality (76.2± 1.9% and 75.9± 1.9%), viability (58.2 ± 1.1%, 59.1 ± 1.1%) and lower significant of lipid peroxidation (2.53 ± 0.08 nmol/ml, 2.49 ± 0.08 nmol/ml) compared to control group containing no LC. Lower motility, progressive motility, and viability were observed in frozen-thawed sperm in extender containing 8 mM LC (35.8± 1.7%, 9.6± 1.2% and 27.1 ± 1.2%, respectively) compared to control. Morphology and mitochondrial activity were not affected by different concentrations of LC. Our results showed that supplementation of Beltsville extender with 1 and 2 mM LC significantly improved the quality of rooster sperm quality after freeze-thawing. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    Science.gov (United States)

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Effect of Acetyl-L-Carnitine on Antioxidant Status, Lipid Peroxidation, and Oxidative Damage of Arsenic in Rat.

    Science.gov (United States)

    Sepand, Mohammad Reza; Razavi-Azarkhiavi, Kamal; Omidi, Ameneh; Zirak, Mohammad Reza; Sabzevari, Samin; Kazemi, Ali Reza; Sabzevari, Omid

    2016-05-01

    Arsenic (As) is a widespread environmental contaminant present around the world in both organic and inorganic forms. Oxidative stress is postulated as the main mechanism for As-induced toxicity. This study was planned to examine the protective effect of acetyl-L-carnitine (ALC) on As-induced oxidative damage in male rats. Animals were randomly divided into four groups of control (saline), sodium arsenite (NaAsO2, 20 mg/kg), ALC (300 mg/kg), and NaAsO2 plus ALC. Animals were dosed orally for 28 successive days. Blood and tissue samples including kidney, brain, liver, heart, and lung were collected on the 28th day and evaluated for oxidative damage and histological changes. NaAsO2 exposure caused a significant lipid peroxidation as evidenced by elevation in thiobarbituric acid-reactive substances (TBARS). The activity of antioxidant enzymes such as glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), as well as sulfhydryl group content (SH group) was significantly suppressed in various organs following NaAsO2 treatment (P < 0.05). Furthermore, NaAsO2 administration increased serum values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and bilirubin. Our findings revealed that co-administration of ALC and NaAsO2 significantly suppressed the oxidative damage induced by NaAsO2. Tissue histological studies have confirmed the biochemical findings and provided evidence for the beneficial role of ALC. The results concluded that ALC attenuated NaAsO2-induced toxicity, and this protective effect may result from the ability of ALC in maintaining oxidant-antioxidant balance.

  8. Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

    Science.gov (United States)

    Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

    2018-06-01

    This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    Directory of Open Access Journals (Sweden)

    L.C. Carnevali Jr

    2012-08-01

    Full Text Available We examined the capacity of high-intensity intermittent training (HI-IT to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g were randomly distributed into 3 groups: sedentary (Sed, N = 5, HI-IT (N = 10, and moderate-intensity continuous training (MI-CT, N = 10. The trained groups were exercised for 8 weeks with a 10% (HI-IT and a 5% (MI-CT overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01, as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01 and lipoprotein lipase (LPL; P < 0.05. Lactate dehydrogenase also presented a higher maximal activity (nmol·min-1·mg protein-1 in HI-IT (around 83%. We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a "time-efficient" strategy inducing metabolic adaptation.

  10. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    Energy Technology Data Exchange (ETDEWEB)

    Carnevali, L.C. Jr. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Centro Universitário Ítalo-Brasileiro (Unítalo), São Paulo SP (Brazil); Eder, R.; Lira, F.S. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Lima, W.P. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Instituto Federal de Educação,Ciência e Tecnologia de São Paulo, São Paulo SP (Brazil); Gonçalves, D.C. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Zanchi, N.E. [Laboratorio de Nutrição e Metabolismo Aplicado à Atividade Motora, Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo SP (Brazil); Centro de Pesquisa do Genoma Humano, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Nicastro, H. [Laboratorio de Nutrição e Metabolismo Aplicado à Atividade Motora, Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo SP (Brazil); Lavoie, J.M. [Department of Kinesiology, University of Montreal, Montreal (Canada); Seelaender, M.C.L. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-06-29

    We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min{sup −1}·mg protein{sup −1}) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a “time-efficient” strategy inducing metabolic adaptation.

  11. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    International Nuclear Information System (INIS)

    Carnevali, L.C. Jr.; Eder, R.; Lira, F.S.; Lima, W.P.; Gonçalves, D.C.; Zanchi, N.E.; Nicastro, H.; Lavoie, J.M.; Seelaender, M.C.L.

    2012-01-01

    We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min −1 ·mg protein −1 ) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a “time-efficient” strategy inducing metabolic adaptation

  12. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, A D; Lanzoni, C; Ricchieri, F; Santagni, S; Rattighieri, E; Chierchia, E; Monteleone, P; Jasonni, V M

    2011-04-01

    Hypothalamic amenorrhea (HA) is characterized by neuroendocrine impairment that, in turn, negatively modulates endocrine function, mainly within the reproductive axis. HA presents with hypo-LH, hypoestrogenism and, until now, a definite therapeutic strategy has not yet been found. The aim of the following study was to test the efficacy of acetyl-L-carnitine (ALC) administration in HA-affected subjects. Twenty-four patients affected by stress-induced HA were divided into two groups according to LH plasma levels: group A, hypo-LH (LH≤3 mIU/ml; no.=16), and group B, normo-LH (LH>3 mIU/ml; no.=8), were treated with ALC (1 g/day, per os) for 16 weeks. Patients underwent baseline hormonal assessment, pulsatility test (for LH and FSH), naloxone test (for LH, FSH and cortisol) both before and after 16 weeks of treatment. Under ALC administration hypo-LH patients showed a significant increase in LH plasma levels (from 1.4±0.3 to 3.1±0.5 mIU/ml, p<0.01) and in LH pulse amplitude (p<0.001). No changes were observed in the normo-LH group. LH response to naloxone was restored under ALC therapy. Maximal LH response and area under the curve under naloxone were significantly increased (p<0.05 and p<0.01, respectively). No changes were observed in the normo-LH patients. Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea.

  13. The Effect of L-Carnitine, Hypotaurine, and Taurine Supplementation on the Quality of Cryopreserved Chicken Semen

    Directory of Open Access Journals (Sweden)

    Agnieszka Partyka

    2017-01-01

    Full Text Available The objective of this study was to investigate the effect of L-carnitine (LC, hypotaurine (HT, and taurine (T on the quality of frozen-thawed chicken semen. Pooled semen samples were divided into seven aliquots (control, 1 mM LC, 5 mM LC, 1 mM HT, 10 mM HT, 1 mM T, and 10 mM T and subjected to cryopreservation. Postthaw sperm motility was determined by IVOS system and sperm characteristics were assessed with fluorochromes and flow cytometry. The highest sperm motility and the highest percentage of viable sperm were in the HT1 group (P<0.01 and P<0.05 following cryopreservation. After thawing, we observed a higher percentage of sperm without apoptosis and membrane reorganization changes in the LC1 and T1 group when compared to the control (P<0.05. There was a higher percentage of live sperm without lipid peroxidation (LPO in all treatments (P<0.01; P<0.05, when compared to the control group. The percentage of sperm with high mitochondrial potential significantly increased with LC1, T1, and T10 (P<0.05. Supplementation of the diluent with LC1, LC5, and T1 significantly (P<0.05 reduced DNA susceptibility to fragmentation, compared to the control and HT1 groups. These results indicate that the addition of examined antioxidants improves the quality of cryopreserved chicken semen.

  14. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    Directory of Open Access Journals (Sweden)

    Vuslat Yurut-Caloglu

    2015-01-01

    Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

  15. Activation of liver carnitine palmitoyltransferase-1 and mitochondrial acetoacetyl-CoA thiolase is associated with elevated ketone body levels in the elasmobranch Squalus acanthias.

    Science.gov (United States)

    Treberg, Jason R; Crockett, Elizabeth L; Driedzic, William R

    2006-01-01

    Elasmobranch fishes are an ancient group of vertebrates that have unusual lipid metabolism whereby storage lipids are mobilized from the liver for peripheral oxidation largely as ketone bodies rather than as nonesterified fatty acids under normal conditions. This reliance on ketones, even when feeding, implies that elasmobranchs are chronically ketogenic. Compared to specimens sampled within 2 d of capture (recently captured), spiny dogfish Squalus acanthias that were held for 16-33 d without apparent feeding displayed a 4.5-fold increase in plasma concentration of d- beta -hydroxybutyrate (from 0.71 to 3.2 mM) and were considered ketotic. Overt activity of carnitine palmitoyltransferase-1 in liver mitochondria from ketotic dogfish was characterized by an increased apparent maximal activity, a trend of increasing affinity (reduced apparent K(m); P=0.09) for l-carnitine, and desensitization to the inhibitor malonyl-CoA relative to recently captured animals. Acetoacetyl-CoA thiolase (ACoAT) activity in isolated liver mitochondria was also markedly increased in the ketotic dogfish compared to recently captured fish, whereas no difference in 3-hydroxy-3-methylglutaryl-CoA synthase activity was found between these groups, suggesting that ACoAT plays a more important role in the activation of ketogenesis in spiny dogfish than in mammals and birds.

  16. Technetium-99m sestamibi leg scintigraphy for non-invasive assessment of propionyl-l-carnitine induced changes in skeletal muscle metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Cittanti, C. [Department of Nuclear Medicine, University of Ferrara (Italy); Colamussi, P. [Department of Nuclear Medicine, University of Ferrara (Italy); Giganti, M. [Department of Nuclear Medicine, University of Ferrara (Italy); Orlandi, C. [MEDCO Research, Inc., North Carolina (United States); Uccelli, L. [Department of Nuclear Medicine, University of Ferrara (Italy); Manfrini, S. [Surgical Pathology Institute, University of Ferrara (Italy); Azzena, G. [Surgical Pathology Institute, University of Ferrara (Italy); Piffanelli, A. [Department of Nuclear Medicine, University of Ferrara (Italy)

    1997-07-01

    Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest {sup 99m}Tc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf {sup 99m}Tc-sestamibi uptake, in comparison with baseline values (P<0.001); (b) the absence of statistically significant modifications of Doppler blood flow indices of the lower limbs. In conclusion, after chronic administration of PLC, a significant increment in skeletal muscle uptake of {sup 99m}Tc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics. (orig.). With 4 figs., 4 tabs.

  17. Technetium-99m sestamibi leg scintigraphy for non-invasive assessment of propionyl-l-carnitine induced changes in skeletal muscle metabolism

    International Nuclear Information System (INIS)

    Cittanti, C.; Colamussi, P.; Giganti, M.; Orlandi, C.; Uccelli, L.; Manfrini, S.; Azzena, G.; Piffanelli, A.

    1997-01-01

    Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest 99m Tc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf 99m Tc-sestamibi uptake, in comparison with baseline values (P 99m Tc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics. (orig.). With 4 figs., 4 tabs

  18. CHANGES IN MAXIMAL STRENGTH AND BODY COMPOSITION AFTER DIFFERENT METHODS OF DEVELOPING MUSCLE STRENGTH AND SUPPLEMENTATION WITH CREATINE, L-CARNITINE AND HMB

    Directory of Open Access Journals (Sweden)

    M Kruszewski

    2011-06-01

    Full Text Available The aim of the present study was to assess the effects of bodybuilding training combined with administration of L-carnitine, weightlifting training combined with administration of creatine, and isometric training combined with administration of β-hydroxy-β-methylbutyrate (HMB on maximal strength and body composition of athletes. The studies were conducted on groups of beginners practising bodybuilding training (n=63 and isometric training (n=69 as well as on a group of advanced powerlifters (n=50 practising weightlifting training. The obtained results indicate that the most desirable and beneficial supportive effect in strength sports was exhibited by HMB. No significant differences in body composition of subjects practising bodybuilding training were detected between those who were given L-carnitine and those who received placebo, an observation confirming controversies over the capacity of the former to reduce fat content. However, significant differences in maximal strength were demonstrated between the examined groups of athletes. Significant differences in the examined parameters were also detected within the group of advanced powerlifters practising weightlifting between those who were supplemented with creatine and those who were given placebo. Thus, the use of creatine in the development of physical capacity in advanced athletes may be advisable.

  19. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.

    Science.gov (United States)

    Hussein, Abdelaziz M; Adel, Mohamed; El-Mesery, Mohamed; Abbas, Khaled M; Ali, Amr N; Abulseoud, Osama A

    2018-03-14

    l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score ( p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure ( p l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) ( p l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 ( p l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

  20. Abundance of specific mRNA transcripts impacts hatching success in European eel, Anguilla anguilla L

    DEFF Research Database (Denmark)

    Rozenfeld, Christoffer; Butts, Ian A.E.; Tomkiewicz, Jonna

    2016-01-01

    -tubulin, insulin-like growth factor 2 (igf2), nucleoplasmin (npm2), prohibitin 2 (phb2), phosphatidylinositol glycan biosynthesis class F protein 5 (pigf5), and carnitine O-palmitoyltransferase liver isoform-like 1 (cpt1) are associated with embryonic developmental competence in other teleosts. Here, the relations...... and no hatching groups for any of the selected genes at 0, 2.5, and 5 HPF. However, at 30 HPF the hatch group showed significantly higher abundance of cpt1a, cpt1b, β-tubulin, phb2, and pigf5 transcripts than the no hatch group. Therefore, these results indicate that up-regulation of the transcription...

  1. L-carnitine is a survival factor for chilled storage of rooster semen for a long time.

    Science.gov (United States)

    Fattah, A; Sharafi, M; Masoudi, R; Shahverdi, A; Esmaeili, V

    2017-02-01

    Rooster sperm is sensitive to cooling, which restricts procedures to store sperms for extended periods of time for artificial insemination of commercial flocks. This study was conducted to evaluate the suitability of adding L-carnitine (LC) to chilled-storage of rooster sperm and its effects on sperm quality parameters and its fertility potential during storage at 5 °C. Pooled semen from roosters were divided into six equal aliquots and diluted with media supplemented with different concentrations of LC (0, 0.5, 1, 2, 4 and 8 mM LC). Diluted semen samples were cooled to 5 °C and stored over 48 h. Motility, viability, membrane functionality, lipid peroxidation and mitochondria activity of the sperm were assessed at 0, 24 and 48 h of storage. Moreover, fertility potential of chilled stored sperm was considered at 24 h of storage. While sperm quality was not affected by LC at the beginning of storage (0 h), supplementation of extender with 1 and 2 mM of LC significantly improved the percentage of sperm motility, viability, membrane integrity and mitochondria activity at 24 h and 48 h compared to other groups. Lipid peroxidation was significantly reduced in sperm samples diluted with 1 and 2 mM LC at 24 h (2.15 ± 0.52 nmol/ml and 2.21 ± 0.52 nmol/ml) and 48 h (3.42 ± 0.49 nmol/ml and 3.38 ± 0.49 nmol/ml) compared to other groups. Furthermore, fertility rates during artificial insemination using sperms cooled for 24 h in the presence of 1 and 2 mM LC were significantly higher (78%) than in the control group (64%). These findings suggest that optimum doses of LC could protect rooster sperm against cool storage-induced functional and structural damages. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics

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    Tucker Patrick S

    2009-06-01

    Full Text Available Abstract Background Resting and postprandial oxidative stress is elevated in those with metabolic disorders such as diabetes. Antioxidant supplementation may attenuate the rise in oxidative stress following feeding. Therefore we sought to determine the effects of acetyl L-carnitine arginate (ALCA on resting and postprandial biomarkers of glucose and lipid metabolism, as well as oxidative stress. Methods Twenty-nine pre-diabetic men and women were randomly assigned to either 3 g·day-1 of ALCA (n = 14; 31 ± 3 yrs or placebo (n = 15; 35 ± 3 yrs in a double-blind design, to consume for eight weeks. Fasting blood samples were taken from subjects both pre and post intervention. After each fasting sample was obtained, subjects consumed a high fat, high carbohydrate meal and additional blood samples were taken at 1, 2, 4, and 6 hours post meal. Samples were analyzed for a variety of metabolic variables (e.g., glucose, HbA1c, lipid panel, C-reactive protein, nitrate/nitrite, and several markers of oxidative stress. Area under the curve (AUC was calculated for each variable measured post meal, both pre and post intervention. Results ALCA, but not placebo, resulted in an increase in nitrate/nitrite (25.4 ± 1.9 to 30.1 ± 2.8 μmol·L-1 from pre to post intervention, with post intervention values greater compared to placebo (p = 0.01. No other changes of statistical significance were noted (p > 0.05, although ALCA resulted in slight improvements in glucose (109 ± 5 to 103 ± 5 mg·dL-1, HbA1c (6.6 ± 1.1 to 6.2 ± 1.2%, and HOMA-IR (3.3 ± 1.3 to 2.9 ± 1.2. AUC postprandial data were not statistically different between ALCA and placebo for any variable (p > 0.05. However, nitrate/nitrite demonstrated a moderate effect size (r = 0.35 for increase from pre (139.50 ± 18.35 μmol·L-1·6 hr-1 to post (172.40 ± 21.75 μmol·L-1·6 hr-1 intervention with ALCA, and the magnitude of decrease following feeding was not as pronounced as with placebo

  3. Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Lefort, Natalie; Glancy, Brian; Bowen, Benjamin

    2010-01-01

    the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine...

  4. Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine.

    Science.gov (United States)

    Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew

    2005-08-01

    A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound

  5. Modelling and analysis of central metabolism operating regulatory interactions in salt stress conditions in a L-carnitine overproducing E. coli strain.

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    Guido Santos

    Full Text Available Based on experimental data from E. coli cultures, we have devised a mathematical model in the GMA-power law formalism that describes the central and L-carnitine metabolism in and between two steady states, non-osmotic and hyperosmotic (0.3 M NaCl. A key feature of this model is the introduction of type of kinetic order, the osmotic stress kinetic orders (g(OSn, derived from the power law general formalism, which represent the effect of osmotic stress in each metabolic process of the model.By considering the values of the g(OSn linked to each metabolic process we found that osmotic stress has a positive and determinant influence on the increase in flux in energetic metabolism (glycolysis; L-carnitine biosynthesis production; the transformation/excretion of Acetyl-CoA into acetate and ethanol; the input flux of peptone into the cell; the anabolic use of pyruvate and biomass decomposition. In contrast, we found that although the osmotic stress has an inhibitory effect on the transformation flux from the glycolytic end products (pyruvate to Acetyl-CoA, this inhibition is counteracted by other effects (the increase in pyruvate concentration to the extent that the whole flux increases. In the same vein, the down regulation exerted by osmotic stress on fumarate uptake and its oxidation and the production and export of lactate and pyruvate are reversed by other factors up to the point that the first increased and the second remained unchanged.The model analysis shows that in osmotic conditions the energy and fermentation pathways undergo substantial rearrangement. This is illustrated by the observation that the increase in the fermentation fluxes is not connected with fluxes towards the tricaboxylic acid intermediates and the synthesis of biomass. The osmotic stress associated with these fluxes reflects these changes. All these observations support that the responses to salt stress observed in E. coli might be conserved in halophiles.Flux evolution

  6. Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study.

    Science.gov (United States)

    Evans, Malkanthi; Guthrie, Najla; Pezzullo, John; Sanli, Toran; Fielding, Roger A; Bellamine, Aouatef

    2017-01-01

    Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary objective, we sought to assess the effect of a novel combination of L-Carnitine, creatine and leucine on muscle mass and performance in older subjects. Forty-two healthy older adults aged 55-70 years were randomized to receive either a novel L-Carnitine (1500 mg), L-leucine (2000 mg), creatine (3000 mg), Vitamin D3 (10 μg) (L-Carnitine-combination) product ( n  = 14), L-Carnitine (1500 mg) ( n  = 14), or a placebo ( n  = 14) for eight weeks. We evaluated body mass by DXA, upper and lower strength by dynamometry, and walking distance by a 6-min walk test at baseline and after eight weeks of intervention. These measures, reflecting muscle mass, functional strength and mobility have been combined to generate a primary composite score. Quality of life, blood safety markers, and muscle biopsies for protein biomarker analysis were also conducted at baseline and the end of the study. The primary composite outcome improved by 63.5 percentage points in the L-Carnitine-combination group vs. placebo ( P  = 0.013). However, this composite score did not change significantly in the L-Carnitine group ( P =  0.232), and decreased slightly in the placebo group ( P =  0.534). Participants supplemented with the L-Carnitine-combination showed a 1.0 kg increase in total lean muscle mass ( P  = 0.013), leg lean muscle mass (0.35 kg, P =  0.005), and a 1.0 kg increase in lower leg strength ( P  = 0.029) at week 8. In addition, these increases were significant when compared to the placebo group (P =  0.034, P =  0.026, and P =  0.002, respectively). Total mTOR protein expression was increased in participants in the L-Carnitine-combination group at the end of

  7. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70

    Directory of Open Access Journals (Sweden)

    Abdelaziz M. Hussein

    2018-03-01

    Full Text Available l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal (negative control or pentylenetetrazole (PTZ 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car (100 mg/kg/day × 4 weeks (PTZ + l-Car, while the second group received saline (PTZ + Sal. Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score (p = 0.0002 that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure (p < 0.0001 and shortened seizure duration (p = 0.028. In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA (p < 0.0001 and reduced the activity of catalase enzyme (p = 0.0006 and increased antioxidant GSH activity (p < 0.0001. Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 (p < 0.0001 and β-catenin (p < 0.0001. Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

  8. Enthalpic pairwise self-association of L-carnitine in aqueous solutions of some alkali halides at T = 298.15 K

    International Nuclear Information System (INIS)

    Wang, Hua-Qin; Cheng, Wei-Na; Zhu, Li-Yuan; Hu, Xin-Gen

    2016-01-01

    Highlights: • Dilution enthalpies of L-carnitine in aqueous alkali halide solutions by ITC. • The second virial coefficients of enthalpy (h_2) have been calculated. • The values of h_2 increase with increasing molalities of aqueous salt solutions. • The signs of h_2 turn from negative in pure water to positive in salt solutions. • The trends is ascribed to the salt effects on pairwise self-associations. - Abstract: Knowledge of the influence of ions of various nature on intermolecular hydrophilic and hydrophobic interactions in solutions is required in many research fields. In this paper, dilution enthalpies of zwitterion L-carnitine in aqueous NaCl, KCl and NaBr solutions of various molalities (b = 0 to 3.0 mol · kg"−"1) have been determined respectively at T = (298.15 ± 0.01) K and p = (0.100 ± 0.005) MPa by isothermal titration calorimetry (ITC). In light of the MacMillan–Mayer theory, the 2nd virial enthalpic coefficients (h_2) have been calculated. The h_2 coefficients increase gradually with increasing molality (b) of the three aqueous alkali halides solutions, from small negative values in pure water to relatively larger positive values in solution. The trends of h_2 coefficients are ascribed to the salt effects on the balance between hydrophilic and hydrophobic interactions in pairwise self-associations. It is considered that the size of cations and anions exert influences on h_2 coefficients through their surface charge densities and hydration (or dehydration) abilities.

  9. Effect of Caffeine Co-Ingested with Carnitine on Weight, Body-Fat Percent, Serum Leptin and Lipid Profile Changes in Male Teen Soccer Players: a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Saeed Shirali

    2016-10-01

    Full Text Available Background: Weight loss and decreasing the Body fat percentage (BF% is motivated to optimize performance. In order to achieve these, many supplements are used by athletes, however the possible negative or synergic effects have not been fully described in the literature, specifically in humans. The present study was conducted to investigate the co-administration effects of two common used supplements in body weight and BF% management to recommend athletes for safe weight and BF% reduction. Materials and Methods: In the present double-blind, randomized, parallel, placebo-controlled study, the effect of six-week co-administration of caffeine and carnitine was determined on changes in body weight (BW, BF%, serum leptin concentration and lipid profile (triglyceride, HDL Cholesterol, LDL Cholesterol and Total Cholesterol, fasting blood glucose (FBG, and free fatty acid (FFA changes. Twenty eight male teen soccer players  from Ahvaz-Iran, were divided in three groups (group CafPlc, caffeine (6 mg/kg/day + dextrose; group CafCar, caffeine (6 mg/kg/day + carnitine (2g; and group Plc, dextrose. Results: Caffeine-carnitine had a lowering effect on BW (P=0.02 and BF% (P=0.03, compared to caffeine alone and placebo in male teen soccer players (mean age of 16.92 ± 0.76 years. TG was significantly decreased in CafCar (P=0.04. FFA levels were increased in CafCar (P=0.04 and there was significant differences between CafCar and Plc groups (P=0.01. FBG was increased in both CafPlc and CafCar (P=0.01 and P=0.02, respectively, with no significant differences between groups. Conclusion: The synergistic effect of caffeine-carnitine might be suggested to decrease the BF% and BW, besides it may prevent the increment of FFA levels; however it should be prescribed cautiously since it increased FBG levels.

  10. Cotransporting Ion is a Trigger for Cellular Endocytosis of Transporter-Targeting Nanoparticles: A Case Study of High-Efficiency SLC22A5 (OCTN2)-Mediated Carnitine-Conjugated Nanoparticles for Oral Delivery of Therapeutic Drugs.

    Science.gov (United States)

    Kou, Longfa; Yao, Qing; Sun, Mengchi; Wu, Chunnuan; Wang, Jia; Luo, Qiuhua; Wang, Gang; Du, Yuqian; Fu, Qiang; Wang, Jian; He, Zhonggui; Ganapathy, Vadivel; Sun, Jin

    2017-09-01

    OCTN2 (SLC22A5) is a Na + -coupled absorption transporter for l-carnitine in small intestine. This study tests the potential of this transporter for oral delivery of therapeutic drugs encapsulated in l-carnitine-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (LC-PLGA NPs) and discloses the molecular mechanism for cellular endocytosis of transporter-targeting nanoparticles. Conjugation of l-carnitine to a surface of PLGA-NPs enhances the cellular uptake and intestinal absorption of encapsulated drug. In both cases, the uptake process is dependent on cotransporting ion Na + . Computational OCTN2 docking analysis shows that the presence of Na + is important for the formation of the energetically stable intermediate complex of transporter-Na + -LC-PLGA NPs, which is also the first step in cellular endocytosis of nanoparticles. The transporter-mediated intestinal absorption of LC-PLGA NPs occurs via endocytosis/transcytosis rather than via the traditional transmembrane transport. The portal blood versus the lymphatic route is evaluated by the plasma appearance of the drug in the control and lymph duct-ligated rats. Absorption via the lymphatic system is the predominant route in the oral delivery of the NPs. In summary, LC-PLGA NPs can effectively target OCTN2 on the enterocytes for enhancing oral delivery of drugs and the critical role of cotransporting ions should be noticed in designing transporter-targeting nanoparticles. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. [Effects of fatigue and restraint stress on the expression of carnitine palmitoyltransferase-I and 5-hydroxytryptamine receptors in aorta of rats].

    Science.gov (United States)

    Wei, Cong; Han, Jian-ke; Wang, Hong-tao; Jia, Zhen-hua; Chang, Li-Ping; Wu, Yi-ling

    2011-04-05

    To investigate the effect of fatigue and restraint stress on the expressions of CPT (carnitine palmitoyltransferase)-I, PPAR (peroxisome proliferator-activated receptor) δ, 5-HT (hydroxytryptamine) 1D and 5-HT2A receptors in aorta of rats. A total of 45 healthy male Wistar rats were randomly divided into control group, excessive fatigue group and restraint stress group (n = 15 each). The general condition, morphological changes of aortic endothelium cell and the blood levels of ET-1 (endothelin) and NO (nitric oxide) were observed. The real-time reverse transcription PCR (polymerase chain reaction) and Western blot were used to detect the gene and protein expressions of CPT-I, PPAR δ, 5-HT1D and 5-HT2A receptors in aorta. Compared with control group, the structural damages of endothelial cell were induced by excessive fatigue and restraint stress. The plasma levels of ET-1 increased [(124 ± 18) ng/L vs (161 ± 18) ng/L, (154 ± 17) ng/L] (P fatigue rats, [(1.23 ± 0.21) vs (0.42 ± 0.05)], [(1.09 ± 0.10) vs (0.25 ± 0.07)] (P fatigue rats, [(1.32 ± 0.07) vs (0.83 ± 0.04)], [(1.41 ± 0.05) vs. (0.75 ± 0.06)]; the mRNA and protein expressions of 5-HT1D receptor decreased in excessive fatigue rats and restraint stress rats, [(1.10 ± 0.15) vs (0.46 ± 0.13), (0.45 ± 0.02)], [(1.19 ± 0.05) vs (0.71 ± 0.06), (0.70 ± 0.05)] (P fatigue rats and restraint stress rats, [(0.99 ± 0.08) vs (6.73 ± 0.46), (7.01 ± 1.56)], [(0.64 ± 0.03) vs (0.79 ± 0.05), (0.82 ± 0.03)] (P fatigue and restraint stress can injure the structure and function of endothelial cell. The changes in energy of abnormal carnitine metabolism and 5-HT receptors may play important roles.

  12. [Effects of L-carnitine on the apoptosis of spermatogenic cells and epididymal sperm count and motility in rats with diabetes mellitus].

    Science.gov (United States)

    Kang, Ning; Ma, Jie-hua; Zhou, Xin; Fan, Xiao-bo; Shang, Xue-jun; Huang, Yu-feng

    2011-05-01

    To explore the effects of L-carnitine (LC) on the apoptosis of spermatogenic cells and on the count and motility of epididymal sperm in rats with diabetes mellitus (DM). Twenty-four SD rats (200-230 g) were randomly divided into a control group, a DM model group and an LC group. After the establishment of DM models in the latter two groups by injection of streptozotocin (STZ) at 65 mg/kg, the controls and DM models were treated intragastrically with physiological saline, while the rats in the LC group with LC at 300 mg/kg, all for 6 consecutive weeks. Twenty-four hours after the last administration, all the rats were killed for the detection of the count and motility of epididymal sperm and the apoptosis of spermatogenic cells. The motilities of caput and cauda epididymal sperm were (53.7 +/- 1.8)% and (60.3 +/- 1.6)% in the LC group, significantly higher than in the DM model group ([32.2 +/- 2.0]% and [40.5 +/- 1.4]%, P count of cauda epididymal sperm was (25.5 +/- 1.1) x 10(6)/100 mg in the DM models, and was increased to (32.0 +/- 1.5) x 10(6)/100 mg after LC treatment (P sperm count, improved sperm motility, and reduced the apoptosis of spermatogenic cells in rats with DM.

  13. Treatment with acetyl-L-carnitine exerts a neuroprotective effect in the sciatic nerve following loose ligation: a functional and microanatomical study

    Directory of Open Access Journals (Sweden)

    Daniele Tomassoni

    2018-01-01

    Full Text Available Peripheral neuropathies are chronic painful syndromes characterized by allodynia, hyperalgesia and altered nerve functionality. Nerve tissue degeneration represents the microanatomical correlate of peripheral neuropathies. Aimed to improve the therapeutic possibilities, this study investigated the hypersensitivity and the neuromorphological alterations related to the loose ligation of the sciatic nerve in rats. Effects elicited by treatment with acetyl-L-carnitine (ALCAR in comparison to gabapentin were assessed. Axonal injury, reduction of myelin deposition and accumulation of inflammatory cells were detected in damaged nerve. A decrease of phosphorylated 200-kDa neurofilament (NFP immunoreactivity and a redistribution in small clusters of myelin basic like-protein (MBP were observed in ipsilateral nerves. Treatment with ALCAR (100 mg/kg intraperitoneally - i.p. and gabapentin (70 mg/kg i.p. administered bis in die for 14 days induced a significant pain relieving effect. ALCAR, but not gabapentin, significantly countered neuromorphological changes and increased axonal NFP immunoreactivity. These findings indicate that both ALCAR and gabapentin significantly decreased the hypersensitivity related to neuropathic lesions. The observation of the positive ALCAR effect on axonal and myelin sheath alterations in damaged nerve supports its use as neurorestorative agent against neuropathies through mechanism(s consistent to those focused in this study.

  14. Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression. A controlled study in a rat model

    International Nuclear Information System (INIS)

    Uecuencue, H.; Ertekin, M.V.; Yoeruek, O.; Sezen, O.; Oezkan, A.; Erdogan, F.; Kiziltunc, A.; Guendogdu, C.

    2006-01-01

    The aim of this study was to determine the effects of vitamin E (VE) and L-carnitine (LC) supplementation, separately or in combination, on radiation-induced oral mucositis and myelosuppression. Group 1 received no treatment (control). Group 2 received 15 Gray of 60 Co gamma irradiation as a single dose to total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE (IR+VE) or 200 mg/kg day LC (IR+LC) or in combination (IR+VE+LC) respectively. Clinically and histopathologically, assessments of mucosal reactions were performed by two independent experts in Radiation Oncology and Pathology, respectively. Hematologic analyses and antioxidant enzyme evaluations were also performed. Irradiation significantly increased oral mucositis, and decreased thrombocyte and White Blood Cell counts. A significant increase in malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and catalase (CAT) activities in plasma were found in the IR group. VE and LC administration, separately, plus irradiation significantly delayed the starting day, and reduced the severity of, oral mucositis. This administration also reduced a fall in the numbers of thrombocyte and white blood cell (WBC) caused by irradiation, and decreased the MDA level, and increased the activity of SOD and CAT enzymes in the plasma. VE and LC, in combination, plus irradiation did not provide a superior radioprotection against radiation-induced toxicities. (author)

  15. Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos[S

    Science.gov (United States)

    Lemas, Dominick J.; Wiener, Howard W.; O'Brien, Diane M.; Hopkins, Scarlett; Stanhope, Kimber L.; Havel, Peter J.; Allison, David B.; Fernandez, Jose R.; Tiwari, Hemant K.; Boyer, Bert B.

    2012-01-01

    Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL-cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity. PMID:22045927

  16. Cats in Positive Energy Balance Have Lower Rates of Adipose Gain When Fed Diets Containing 188 versus 121 ppm L-Carnitine

    Directory of Open Access Journals (Sweden)

    M. A. Gooding

    2016-01-01

    Full Text Available L-carnitine (LC is included in select adult feline diets for weight management. This study investigated whether feeding adult cats with diets containing either 188 ppm of LC (LC188 or 121 ppm of LC (LC121 and feeding them 120% of maintenance energy requirement (MER resulted in differences in total energy expenditure (EE, metabolic fuel selection, BW, body composition, and behavior. Cats (n=20, 4±1.2 yrs were stratified for BCS and randomly assigned to one of two dietary treatments and fed for 16 weeks. BW was measured weekly, and indirect calorimetry, body composition, physical activity, play motivation, and cognition were measured at baseline and throughout the study. A mixed, repeated measures, ANCOVA model was used. Cats in both treatments gained BW (P0.05. There were no differences in body composition between groups at baseline; however, body fat (g and body fat : lean mass ratio were greater in cats fed LC121 in contrast to cats fed LC188 (P0.05. Supplying dietary LC at a dose of at least 188 ppm may be beneficial for the health and well-being of cats fed above MER.

  17. Hepatic beta-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides.

    Science.gov (United States)

    Peffer, Pasha Lyvers; Lin, Xi; Odle, Jack

    2005-06-01

    A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.

  18. Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation.

    Directory of Open Access Journals (Sweden)

    Cong-Hui Yao

    2018-03-01

    Full Text Available It has been suggested that some cancer cells rely upon fatty acid oxidation (FAO for energy. Here we show that when FAO was reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I (CPT1 with low concentrations of etomoxir, the proliferation rate of various cancer cells was unaffected. Efforts to pharmacologically inhibit FAO more than 90% revealed that high concentrations of etomoxir (200 μM have an off-target effect of inhibiting complex I of the electron transport chain. Surprisingly, however, when FAO was reduced further by genetic knockdown of CPT1, the proliferation rate of these same cells decreased nearly 2-fold and could not be restored by acetate or octanoic acid supplementation. Moreover, CPT1 knockdowns had altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 had been approximately 90% inhibited by etomoxir did not. Lipidomic profiling of mitochondria isolated from CPT1 knockdowns showed depleted concentrations of complex structural and signaling lipids. Additionally, expression of a catalytically dead CPT1 in CPT1 knockdowns did not restore mitochondrial coupling. Taken together, these results suggest that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO.

  19. Replacement of C305 in heart/muscle-type isozyme of human carnitine palmitoyltransferase I with aspartic acid and other amino acids.

    Science.gov (United States)

    Matsuo, Taisuke; Yamamoto, Atsushi; Yamamoto, Takenori; Otsuki, Kaoru; Yamazaki, Naoshi; Kataoka, Masatoshi; Terada, Hiroshi; Shinohara, Yasuo

    2010-04-01

    Liver- and heart/muscle-type isozymes of human carnitine palmitoyltransferase I (L- and M-CPTI, respectively) show a certain similarity in their amino acid sequences, and mutation studies on the conserved amino acids between these two isozymes often show essentially the same effects on their enzymatic properties. Earlier mutation studies on C305 in human M-CPTI and its counterpart residue, C304, in human L-CPTI showed distinct effects of the mutations, especially in the aspect of enzyme stability; however, simple comparison of these effects on the conserved Cys residue between L- and M-CPTI was difficult, because these studies were carried out using different expression systems and distinct amino acids as replacements. In the present study, we carried out mutation studies on the C305 in human M-CPTI using COS cells for the expression system. Our results showed that C305 was replaceable with aspartic acid but that substitution with other amino acids caused both loss of function and reduced expression.

  20. EFECTO DE L-CARNITINA SOBRE EL PESO, NIVELES DE TRIGLICÉRIDOS Y COLESTEROL DE RATONES SOMETIDOS A DIETAS NORMO E HIPERCALÓRICAS | EFFECT OF L-CARNITINE ON WEIGHT, CHOLESTEROL AND TRIGLYCERIDES LEVELS OF MICE RECEIVING NORMAL AND HIGH CALORIC DIETS

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    Luis Ojeda

    2016-11-01

    Full Text Available An experimental study was conducted to determine the effect of L-carnitine on weight and serum lipid levels (triglycerides and total cholesterol on NMRI mice. To do so, a factorial arrangement of treatments 22 under a completely randomized design was carried out. Factors considered were the diet (normal and hypercaloric and the inclusion or not of the L-carnitine supplement. L-carnitine was orally administered at a rate of 2 mg/day. Weight [g], serum triglyceride concentrations [mg·dL-1] and total cholesterol [mg·dL-1] were evaluated. Analysis of variance test and Tukey mean comparisons were applied. Non significant differences were found between the type of diet for weight (F = 4.00; p = 0.0575, and cholesterol (F = 0.09; p = 0.7722, or for the administration of L-carnitine for the weight (F = 1.08; p = 0.3096, and cholesterol (F = 0.13; p = 0.7255. For triglycerides, significant differences between the type of diet (F = 12.73; p = 0.0016, and significant interaction between type of diet and the administration of L-carnitine (F = 5.95; p = 0.0228, were found. This effect suggests that the amino acid combined with a low calorie diet could be considered as an alternative to treat cases of hypertriglyceridemia.

  1. Metabolic Agents that Enhance ATP can Improve Cognitive Functioning: A Review of the Evidence for Glucose, Oxygen, Pyruvate, Creatine, and l-Carnitine

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    Lauren Owen

    2011-08-01

    Full Text Available Over the past four or five decades, there has been increasing interest in the neurochemical regulation of cognition. This field received considerable attention in the 1980s, with the identification of possible cognition enhancing agents or “smart drugs”. Even though many of the optimistic claims for some agents have proven premature, evidence suggests that several metabolic agents may prove to be effective in improving and preserving cognitive performance and may lead to better cognitive aging through the lifespan. Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. There are a number of agents with the potential to improve metabolic activity. Research is now beginning to identify these various agents and delineate their potential usefulness for improving cognition in health and disease. This review provides a brief overview of the metabolic agents glucose, oxygen, pyruvate, creatine, and l-carnitine and their beneficial effects on cognitive function. These agents are directly responsible for generating ATP (adenosine triphosphate the main cellular currency of energy. The brain is the most metabolically active organ in the body and as such is particularly vulnerable to disruption of energy resources. Therefore interventions that sustain adenosine triphosphate (ATP levels may have importance for improving neuronal dysfunction and loss. Moreover, recently, it has been observed that environmental conditions and diet can affect transgenerational gene expression via epigenetic mechanisms. Metabolic agents might play a role in regulation of nutritional epigenetic effects. In summary, the reviewed metabolic agents represent a promising strategy for improving cognitive function and possibly slowing or preventing cognitive decline.

  2. Acetyl-L-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats.

    Science.gov (United States)

    Singh, Sonu; Mishra, Akanksha; Srivastava, Neha; Shukla, Rakesh; Shukla, Shubha

    2018-01-01

    Parkinson's disease is accompanied by nonmotor symptoms including cognitive impairment, which precede the onset of motor symptoms in patients and are regulated by dopamine (DA) receptors and the mesocorticolimbic pathway. The relative contribution of DA receptors and astrocytic glutamate transporter (GLT-1) in cognitive functions is largely unexplored. Similarly, whether microglia-derived increased immune response affects cognitive functions and neuronal survival is not yet understood. We have investigated the effect of acetyl-L-carnitine (ALCAR) on cognitive functions and its possible underlying mechanism of action in 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats. ALCAR treatment in 6-OHDA-lesioned rats improved memory functions as confirmed by decreased latency time and path length in the Morris water maze test. ALCAR further enhanced D1 receptor levels without altering D2 receptor levels in the hippocampus and prefrontal cortex (PFC) regions, suggesting that the D1 receptor is preferentially involved in the regulation of cognitive functions. ALCAR attenuated microglial activation and release of inflammatory mediators through balancing proinflammatory and anti-inflammatory cytokines, which subsequently enhanced the survival of mature neurons in the CA1, CA3, and PFC regions and improved cognitive functions in hemiparkinsonian rats. ALCAR treatment also improved glutathione (GSH) content, while decreasing oxidative stress indices, inducible nitrogen oxide synthase (iNOS) levels, and astrogliosis resulting in the upregulation of GLT-1 levels. Additionally, ALCAR prevented the loss of dopaminergic (DAergic) neurons in ventral tagmental area (VTA)/substantia nigra pars compacta (SNpc) regions of 6-OHDA-lesioned rats, thus maintaining the integrity of the nigrostriatal pathway. Together, these results demonstrate that ALCAR treatment in hemiparkinsonian rats ameliorates neurodegeneration and cognitive deficits, hence suggesting its therapeutic potential in

  3. The Efficacy of Medical Treatment of Peyronie’s Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor

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    Tae Yong Park

    2016-04-01

    Full Text Available Purpose: This study was designed to evaluate the efficacy of medical treatment of Peyronie’s disease. Materials and Methods: A total of 109 patients with Peyronie’s disease who had been treated from January 2011 to December 2014 were retrospectively reviewed in this study. Forty-four patients (Group 1 were treated with 12 mg of potassium para-aminobenzoate daily. Sixty-five patients (Group 2 were treated with combination therapy: tamoxifen (20 mg and acetyl-L-carnitine (300 mg twice daily in addition to a phosphodiesterase type 5 inhibitor. Ability to perform sexual intercourse, pain during erection, size of plaque, and penile curvature angle were assessed. Results: In Group 1, 30 of 44 patients (68.2% discontinued treatment within 12 weeks, while 5 patients (7.7% in Group 2 discontinued treatment. Pain during erection and plaque size were improved in both groups but showed no statistical difference due to the high dropout rate in Group 1. In both groups, penile curvature was improved, but demonstrated no statistical difference between the treatment groups. However, combination therapy demonstrated a better response rate in patients whose penile curvature angle was less than 30o (44.4% vs. 79.1%, p=0.048. The rate of successful sexual intercourse was significantly higher in Group 2 (42.8% vs. 78.3%, p=0.034. The number of patients who underwent surgical correction despite medical treatment was significantly higher in Group 1 (35.7% vs. 13.3%, p=0.048. Conclusions: Early medical combination therapy in Peyronie’s disease may present better results in patients whose curvature angle is less than 30o.

  4. O uso da L-carnitina como adjuvante no tratamento da miocardiopatia dilatada em criança com Aids Usage of L-carnitine as adjuvant in the treatment of dilated cardiomyopathy in a child with Aids

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    Lourdes Zélia Zanoni

    2011-06-01

    Full Text Available OBJETIVO: Apresentar a resposta cardiovascular à L-carnitina de um paciente com insuficiência cardíaca congestiva decorrente de miocardiopatia dilatada pelo vírus da imunodeficiência humana. DESCRIÇÃO DO CASO: Criança com quadro clínico de insuficiência cardíaca congestiva grave devido à miocardiopatia dilatada pela síndrome de imunodeficiência adquirida. O tratamento para as manifestações clínicas foi instituído, com pouca resposta clínica. Com objetivo de melhorar o desempenho energético/metabólico dos cardiomiócitos, foi instituída terapia com L-carnitina. Observou-se significativa melhora clínica do paciente, em relação ao desempenho cardíaco, mesmo antes do início do tratamento com os fármacos antirretrovirais. COMENTÁRIOS: A L-carnitina é um composto que facilita o transporte dos ácidos graxos de cadeia longa para dentro da mitocôndria. Nesse caso, o uso da L-carnitina parece ser clinica e bioquimicamente justificado.OBJECTIVE: To present the cardiovascular response to L-carnitine of a patient with congestive heart failure caused by dilated cardiomyopathy and human immunodeficiency virus. CASE DESCRIPTION: Child with a clinical history of severe congestive heart failure due to dilated cardiomyopathy caused by acquired immunodeficiency syndrome. The treatment for the symptoms resulted in a poor clinical response. In order to improve the energetic performance/metabolism of cardiomyocytes, therapy with L-carnitine was established. There was significant clinical improvement of the cardiac performance of the patient, even before starting the treatment with antiretroviral drugs. COMMENTS: L-carnitine is a compound that facilitates the transport of long-chain fatty acids into the mitochondria. In this case the administration of L-carnitine appears to be clinically and biochemical justified.

  5. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

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    Kathryn J Swoboda

    2010-08-01

    Full Text Available Valproic acid (VPA has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA in vitro and in vivo.Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1 and an ambulatory group of "walkers" (cohort 2. Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51. Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409. Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03 compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007.This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that

  6. Carnitine palmitoyltransferase 1A (CPT1A): a transcriptional target of PAX3-FKHR and mediates PAX3-FKHR–dependent motility in alveolar rhabdomyosarcoma cells

    International Nuclear Information System (INIS)

    Liu, Lingling; Wang, Yong-Dong; Wu, Jing; Cui, Jimmy; Chen, Taosheng

    2012-01-01

    Alveolar rhabdomyosarcoma (ARMS) has a high propensity to metastasize, leading to its aggressiveness and a poor survival rate among those with the disease. More than 80% of aggressive ARMSs harbor a PAX3-FKHR fusion transcription factor, which regulates cell migration and promotes metastasis, most likely by regulating the fusion protein’s transcriptional targets. Therefore, identifying druggable transcription targets of PAX3-FKHR that are also downstream effectors of PAX3-FKHR–mediated cell migration and metastasis may lead to novel therapeutic approaches for treating ARMS. To identify genes whose expression is directly affected by the level of PAX3-FKHR in an ARMS cellular-context, we first developed an ARMS cell line in which PAX3-FKHR is stably down-regulated, and showed that stably downregulating PAX3-FKHR in ARMS cells significantly decreased the cells’ motility. We used microarray analysis to identify genes whose expression level decreased when PAX3-FKHR was downregulated. We used mutational analysis, promoter reporter assays, and electrophoretic mobility shift assays to determine whether PAX3-FKHR binds to the promoter region of the target gene. We used siRNA and pharmacologic inhibitor to downregulate the target gene of PAX3-FKHR and investigated the effect of such downregulation on cell motility. We found that when PAX3-FKHR was downregulated, the expression of carnitine palmitoyltransferase 1A (CPT1A) decreased. We showed that PAX3-FKHR binds to a paired-domain binding-site in the CPT1A promoter region, indicating that CPT1A is a novel transcriptional target of PAX3-FKHR. Furthermore, downregulating CPT1A decreased cell motility in ARMS cells, indicating that CPT1A is a downstream effector of PAX3-FKHR–mediated cell migration and metastasis. Taken together, we have identified CPT1A as a novel transcriptional target of PAX3-FKHR and revealed the novel function of CPT1A in promoting cell motility. CPT1A may represent a novel therapeutic target for

  7. Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle.

    Science.gov (United States)

    Lefort, Natalie; Glancy, Brian; Bowen, Benjamin; Willis, Wayne T; Bailowitz, Zachary; De Filippis, Elena A; Brophy, Colleen; Meyer, Christian; Højlund, Kurt; Yi, Zhengping; Mandarino, Lawrence J

    2010-10-01

    The contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle. Mitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method. NADH- and FADH(2)-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-DL-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B). We provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.

  8. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to acetyl-L-carnitine and contribution to normal cognitive function (ID 1432) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to acetyl-L-carnitine and contribution to normal cognitive function. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... be drawn for the scientific substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of acetyl-L-carnitine and contribution to normal cognitive function....

  9. Antiketogenic and hypoglycemic effects of aminocarnitine and acylaminocarnitines

    International Nuclear Information System (INIS)

    Jenkins, D.L.; Griffith, O.W.

    1986-01-01

    DL-Aminocarnitine (DL-3-amino-4-trimethyl-aminobutyrate) is a potent, noncovalent inhibitor of carnitine palmitoyltransferase (palmitoyl-CoA:L-carinite O-palmitoyltransferase, EC 2.3.1.21). Here the authors show that decanoyl-DL-aminocarnitine and palmitoyl-DL-aminocarnitine inhibit carnitine palmitoyltransferase in vitro about 7-fold and 100-fold more effectively than does aminocarnitine. Aminocarnitine and its decanoyl and palmitoyl derivatives are active in vivo following oral or parenteral administration and, at doses of 0.3 mmol/kg or less, inhibit the oxidation of [ 14 C]palmitate to 14 CO 2 by 45-70% in mice. Larger doses do not significantly increase the extent of inhibition, a finding suggesting that substantial carnitine palmitoyltransferase-independent long-chain fatty acid oxidation may occur in vivo. Small doses of aminocarnitine and palmitoylaminocarnitine prevent the development of ketoacidemia in fasted, normal mice and reverse the ketoacidemia observed in diabetic mice. Aminocarnitine has a strong hypoglycemic effect in fasted diabetic mice; a single dose (0.3 mmol/kg) normalizes plasma glucose levels within 4-8 hr and remains effective for at least 12 hr

  10. Performance of juvenile turbot (Scophthalmus maximus fed varying dietary L-carnitine levels at different stocking densities Desempenho de juvenis de pregado (Scophthalmus maximus em função da densidade de estocagem e de níveis dietéticos de L-carnitina

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    José Fernando Magalhães Gonçalves

    2010-04-01

    Full Text Available Commercial farming of turbot (Scophthalmus maximus at high stocking densities may lead to growth depression and increasing production costs. Moreover, the high levels of accumulated waste in an intensive system may cause rapid deterioration of water quality, which may undermine the production. L-carnitine is known as a growth-enhancer which shows promise as mitigator of crowding effects. The effects of stocking densities (4, 8, 11 and 14 kg m² on growth performance, feed utilization and body composition were evaluated during 75 days on turbot (75.6 ± 2.8 g fed two dietary L-carnitine levels (40 or 240 mg kg¹. At the end of the feeding trial, total ammonia excretion (TAN was measured postprandially for 24h. Specific growth rate and weight gain decreased with increasing stocking density. Fish held at 4 kg m² had higher final body weight (94-96 g than fish held at higher densities (80-87 g. Protein efficiency ratio was higher in fish held at 4 kg m² (1.33-1.36, in comparison to fish stocked at 8 kg m² (0.98 or 14 kg m² (0.45. Voluntary feed intake decreased from 0.70 to 0.56% BW with increasing stocking density. Dietary L-carnitine supplementation did not affect growth performance and body composition, except for body L-carnitine content which increased from 75 to 128 mg kg¹ BW with supplementation. Fish fed 240 mg L-carnitine supplements had lower TAN that the ones fed 40 mg L-carnitine (p A aquicultura de pregado (Scophthalmus maximus utilizando elevadas densidades pode reduzir o crescimento e aumentar os custos de produção. Elevados níveis de metabolitos gerados nestes sistemas intensivos provocam rápida deterioração da qualidade da água, podendo também comprometer a performance da produção. A L-carnitina atua como potenciadora do crescimento parecendo ser promissora por atenuar alguns desses efeitos. Os efeitos de densidades (4, 8, 11 e 14 kg m² no desempenho do crescimento, composição corporal foram avaliados em pregados

  11. Efeitos da suplementação oral de L-carnitina associada ao treinamento físico na tolerância ao exercício de pacientes com doença pulmonar obstrutiva crônica Influence of oral L-carnitine supplementation combined with physical training on exercise tolerance in patients with chronic obstructive pulmonary disease

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    Audrey Borghi Silva

    2003-12-01

    Full Text Available INTRODUÇÃO: Pacientes portadores de doença pulmonar obstrutiva crônica apresentam redução da tolerância ao exercício físico, principalmente devido à limitação ventilatória. A L-carnitina tem sido utilizada com o objetivo de melhorar a capacidade aeróbia de pacientes com doenças crônicas, porém não existem estudos em pacientes portadores de doença pulmonar obstrutiva crônica. OBJETIVO: Avaliar a influência da suplementação de L-carnitina, associada ao treinamento físico por seis semanas, três vezes por semana em pacientes portadores de doença pulmonar obstrutiva crônica. MÉTODO: A amostra foi constituída de 30 pacientes portadores de doença pulmonar obstrutiva crônica (69 ± 7 anos com volume expiratório forçado no primeiro segundo BACKGROUND: Patients with chronic obstructive pulmonary disease usually present intolerance to physical exertion due to ventilatory limitation. L-carnitine has been used to enhance aerobic capacity in patients with chronic diseases, but no study seems to be available for this patient population. OBJECTIVE: To evaluate the influence of L-carnitine supplementation (2 g/day in chronic obstructive pulmonary disease patients undergoing physical training three times a week for six weeks. METHOD: Patients (mean age 69 ± 7 years, n = 30 with stable chronic obstructive pulmonary disease and < 65% of predicted forced expiratory volume in 1 second (FEV1 were separated into three groups of 10 patients each. Group 1 (G1, n = 10 received physical training and L-carnitine (2 g/day, group 2 (G2, n = 10 received physical training and placebo, and group 3 (G3, n = 10 received only L-carnitine (2 g/day. Spirometry and a 6-minute walking distance test were performed before and after intervention. Plasma levels of free carnitine were measured at the beginning and end of the study. RESULTS: A significant increase in walking distance was found only in G1 and G2 (421 ± 100 to 508 ± 80.7 and 496 ± 78.7 to

  12. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

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    Eduardo Gómez-Gómez

    Full Text Available Carnitine palmitoyltransferase IB (CPT1B and adrenoceptor beta-3 (ADRB3 are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate and fat oxidation (through the non-protein respiratory quotient. These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

  13. Bioconversion of α-linolenic acid to n-3 LCPUFA and expression of PPAR-alpha, acyl Coenzyme A oxidase 1 and carnitine acyl transferase I are incremented after feeding rats with α-linolenic acid-rich oils.

    Science.gov (United States)

    González-Mañán, Daniel; Tapia, Gladys; Gormaz, Juan Guillermo; D'Espessailles, Amanda; Espinosa, Alejandra; Masson, Lilia; Varela, Patricia; Valenzuela, Alfonso; Valenzuela, Rodrigo

    2012-07-01

    High dietary intake of n-6 fatty acids in relation to n-3 fatty acids may generate health disorders, such as cardiovascular and other chronic diseases. Fish consumption rich in n-3 fatty acids is low in Latin America, it being necessary to seek other alternatives to provide α-linolenic acid (ALA), precursor of n-3 LCPUFA (EPA and DHA). Two innovative oils were assayed, chia (Salvia hispanica) and rosa mosqueta (Rosa rubiginosa). This study evaluated hepatic bioconversion of ALA to EPA and DHA, expression of PPAR-α, acyl-Coenzyme A oxidase 1 (ACOX1) and carnitine acyltransferase I (CAT-I), and accumulation of EPA and DHA in plasma and adipose tissue in Sprague-Dawley rats. Three experimental groups were fed 21 days: sunflower oil (SFO, control); chia oil (CO); rosa mosqueta oil (RMO). Fatty acid composition of total lipids and phospholipids from plasma, hepatic and adipose tissue was assessed by gas-liquid chromatography and TLC. Expression of PPAR-α (RT-PCR) and ACOX1 and CAT-I (Western blot). CO and RMO increased plasma, hepatic and adipose tissue levels of ALA, EPA and DHA and decreased n-6:n-3 ratio compared to SFO (p oil.

  14. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to L-carnitine and faster recovery from muscle fatigue after exercise (ID 738, 1492, 1493), skeletal muscle tissue repair (ID 738, 1492, 1493), increase in endurance

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to L-carnitine and faster recovery from muscle fatigue after exercise, skeletal muscle tissue repair, increase in endurance capacity, maintenance of normal blood LDL-cholesterol concentrations, contribution to normal spermatogenesis, “energy metabolism”, and increasing L...

  15. O papel da L-carnitina no estado nutricional e na evolução ecocardiográfica da cardiomiopatia dilatada idiopática da infância The role of L-carnitine in nutritional status and echocardiographic parameters in idiopathic dilated cardiomyopathy in children

    Directory of Open Access Journals (Sweden)

    Vitor M. P. Azevedo

    2005-10-01

    impact of L-carnitine supplementation on the nutritional status and echocardiogram parameters of children with idiopathic dilated cardiomyopathy. METHODS: This was an open label cohort of 11 patients who received L-carnitine (100 mg/kg/day plus the conventional medical treatment, compared with 40 controls, matched for gender and age. The L-carnitine group was weighed 118 times and the controls 264 times. Additionally, the L-carnitine group underwent 65 two-dimensional echocardiograms and the controls 144. Chi-square, Student's t test, Pearson correlation and ANOVA were calculated with alpha = 0.05. RESULTS: For the L-carnitine group: age at presentation = 3.82 years old, 72.7% (p = 0.033 were females younger than 2 years and 90.9% (p = 0.0001 were in functional classes III and IV. There were no deaths during this period. At presentation, no differences were observed in weight percentile (31.2±8.74 vs. 19.6±21.2 (p = 0.29 or z score (-0.68±1.05 vs. -1.16±0.89 (p = 0.24. Increases were observed in both the percentile (p = 0.026 and z score (p = 0.033 after the introduction of L-carnitine. At presentation, there were no differences in ejection fraction (54.9%±3.8 vs. 49.3%±6.6 (p = 0.19, but LV mass/BSA were greater in the L-carnitine group (169.12 g/m²±26.24 vs. 110.67 g/m²±15.62 (p = 0.0005. After the introduction of L-carnitine an increase in ejection fraction (48.3±7 to 67.2±7 (p = 0.044 was observed. LV mass/BSA decreased (164.29g/m²±28.14 to 110.88g/m²±28.88, but without significance (p = 0.089 CONCLUSION: In children with idiopathic dilated cardiomyopathy, supplementation of L-carnitine may be helpful for nutritional and echocardiographic improvement.

  16. A multi-ingredient containing carbohydrate, proteins L-glutamine and L-carnitine attenuates fatigue perception with no effect on performance, muscle damage or immunity in soccer players.

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    Fernando Naclerio

    Full Text Available We investigated the effects of ingesting a multi-ingredient (53 g carbohydrate, 14.5 g whey protein, 5 g glutamine, 1.5 g L-carnitine-L-tartrate supplement, carbohydrate only, or placebo on intermittent performance, perception of fatigue, immunity, and functional and metabolic markers of recovery. Sixteen amateur soccer players ingested their respective treatments before, during and after performing a 90-min intermittent repeated sprint test. Primary outcomes included time for a 90-min intermittent repeated sprint test (IRS followed by eleven 15 m sprints. Measurements included creatine kinase, myoglobin, interleukine-6, Neutrophil; Lymphocytes and Monocyte before (pre, immediately after (post, 1 h and 24 h after exercise testing period. Overall, time for the IRS and 15 m sprints was not different between treatments. However, the perception of fatigue was attenuated (P<0.001 for the multi-ingredient (15.9±1.4 vs. placebo (17.8±1.4 but not for the carbohydrate (17.0±1.9 condition. Several changes in immune/inflammatory indices were noted as creatine kinase peaked at 24 h while Interleukin-6 and myoglobin increased both immediately after and at 1 h compared with baseline (P<0.05 for all three conditions. However, Myoglobin (P<0.05 was lower 1 h post-exercise for the multi-ingredient (241.8±142.6 ng·ml(-1 and CHO (265.4±187.8 ng·ml(-1 vs. placebo (518.6±255.2 ng·ml(-1. Carbohydrate also elicited lower neutrophil concentrations vs. multi-ingredient (3.9±1.5 10(9/L vs. 4.9±1.8 10(9/L, P = 0.016 and a reduced (P<0.05 monocytes count (0.36±0.09 10(9/L compared to both multi-ingredient (0.42±0.09 10(9/L and placebo (0.42±0.12 10(9/L. In conclusion, multi-ingredient and carbohydrate supplements did not improve intermittent performance, inflammatory or immune function. However, both treatments did attenuate serum myoglobin, while only carbohydrate blunted post-exercise leukocytosis.

  17. Influência do treinamento físico aeróbio no transporte mitocondrial de ácidos graxos de cadeia longa no músculo esquelético: papel do complexo carnitina palmitoil transferase Influence of aerobic physical training in the motochondrial transport of long chain fatty acids in the skeletal muscle: role of the carnitine palmitoil transferase

    Directory of Open Access Journals (Sweden)

    Alex Shimura Yamashita

    2008-04-01

    Full Text Available O ácido graxo (AG é uma importante fonte de energia para o músculo esquelético. Durante o exercício sua mobilização é aumentada para suprir as necessidades da musculatura ativa. Acredita-se que diversos pontos de regulação atuem no controle da oxidação dos AG, sendo o principal a atividade do complexo carnitina palmitoil transferase (CPT, entre os quais três componentes estão envolvidos: a CPT I, a CPT II e carnitina acilcarnitina translocase. A função da CPT I durante o exercício físico é controlar a entrada de AG para o interior da mitocôndria, para posterior oxidação do AG e produção de energia. Em resposta ao treinamento físico há um aumento na atividade e expressão da CPT I no músculo esquelético. Devido sua grande importância no metabolismo de lipídios, os mecanismos que controlam sua atividade e sua expressão gênica são revisados no presente estudo. Reguladores da expressão gênica de proteínas envolvidas no metabolismo de lipídios no músculo esquelético, os receptores ativados por proliferadores de peroxissomas (PPAR alfa e beta, são discutidos com um enfoque na resposta ao treinamento físico.Fatty acids are an important source of energy for the skeletal muscle. During exercise, their mobilization is increased to supply the muscle energetic needs. Many points of regulation act in the fatty acids metabolism, where the carnitine palmytoiltransferase (CPT complex is the main control system. Three compounds named CPT I, CPT II and carnitine acyl carnitine translocase (CACT are components of this system. Its function is to control the influx of fatty acids inside the mitochondria for posterior oxidation and energy production. There is a pronounced increase in both activity and gene expression of CPT I in the skeletal muscle in response to exercise. Due to its importance in lipid metabolism, the controlling mechanisms are reviewed in the present study. The modulation of gene expression by peroxisome

  18. Genetics Home Reference: primary carnitine deficiency

    Science.gov (United States)

    ... early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), confusion, vomiting, ... general population is approximately 1 in 100,000 newborns. In Japan, this disorder affects 1 in every ...

  19. Genetics Home Reference: carnitine palmitoyltransferase II deficiency

    Science.gov (United States)

    ... PubMed Isackson PJ, Bennett MJ, Lichter-Konecki U, Willis M, Nyhan WL, Sutton VR, Tein I, Vladutiu ... 27 [updated 2017 Mar 16]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean ...

  20. Genetics Home Reference: carnitine palmitoyltransferase I deficiency

    Science.gov (United States)

    ... may be more common in the Hutterite and Inuit populations. Related Information What information about a genetic ... palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A- ...

  1. Correlações entre os níveis de L-carnitina plasmática, o estado nutricional e a função ventilatória de portadores de doença pulmonar obstrutiva crônica Correlations among the levels of plasmatic L-carnitine, the nutritional status, and the ventilatory function in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Audrey Borghi e Silva

    2005-06-01

    Full Text Available OBJETIVO: Avaliar os níveis de L-carnitina livre no plasma, o estado nutricional, a função pulmonar e a tolerância ao exercício em pacientes com doença pulmonar obstrutiva crônica e verificar as correlações entre a composição corporal e as frações de L-carnitina no plasma. MÉTODOS: Quarenta pacientes entre 66,2±9 anos, com diagnóstico clínico de doença pulmonar obstrutiva crônica, foram divididos em dois grupos: G1, com índice de massa corporal menor que 20kg/m², e G2, com índice de massa corporal maior que 20kg/m². Foram mensurados os parâmetros espirométricos, a tolerância ao exercício no teste de caminhada, a força muscular respiratória, a composição corporal por meio da impedância bioelétrica e as dosagens da L-carnitina plasmática, através de amostras de sangue. RESULTADOS: Foram observados menores valores das variáveis espirométricas (pOBJECTIVE: The objective of this study was to evaluate the levels of free L-carnitine in the plasma, the nutritional condition, the pulmonary function, and the tolerance to exercising in patients with chronic obstructive pulmonary Disease, in order to verify the correlations between body composition and L-carnitine levels in the plasma. METHODS: Forty patients between 66.2±9 years of age, with clinical diagnostics of chronic obstructive pulmonary disease, were divided in two groups: G1, patients with body mass index of less than 20 kg/m², and G2, with Body Mass Index of more than 20 kg/m². There were evaluations of the spirometric variables; the exercise tolerance, through a six-minute walking test; the respiratory muscle strength; the body composition, through the bioelectric impedance; and the free L-carnitine levels in the plasma, through blood exams. RESULTS: The results showed lower values in G1 patients, for the spirometric variables (p<0.01, the respiratory muscle strength, and the L-carnitine levels; however, no difference between the groups was observed

  2. Antihyperlipidemic effect of Acanthopanax senticosus (Rupr. et Maxim) Harms leaves in high-fat-diet fed mice.

    Science.gov (United States)

    Nishida, Miyako; Kondo, Momoko; Shimizu, Taro; Saito, Tetsuo; Sato, Shinji; Hirayama, Masao; Konishi, Tetsuya; Nishida, Hiroshi

    2016-08-01

    Metabolic syndrome is a major risk factor for a variety of obesity-related diseases. Recently, the effects of functional foods have been investigated on lipid metabolism as a means to reduce lipid content in the blood, liver and adipose tissues associated with carnitine O-palmitoyltransferase (CPT) activity. Acanthopanax senticosus (Rupr. et Maxim) Harms (AS) is a medicinal herb possessing a wide spectra of functions including antioxidant, anti-inflammatory and anti-fatigue actions. Despite much research being focused on the cortical roots of AS, little information is available regarding its leaves, which are also expected to promote human health, for example by improving abnormal lipid metabolism. Here, we explored whether AS leaves affect lipid metabolism in mice fed a high-fat diet. The administration of AS to BALB/c mice fed a high-fat diet significantly decreased plasma triglycerides (TG). CPT activity in the liver of these mice was significantly enhanced by AS treatment. These findings indicate that AS leaves have the potential to alleviate increase in plasma TG levels due to high-fat diet intake in mice, possibly by increasing mitochondrial fatty acid β-oxidation, especially via CPT activation. Consequently, daily intake of AS leaves could promote beneficial health effects including the prevention of metabolic syndrome. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  3. Adaptive evolution to a high purine and fat diet of carnivorans revealed by gut microbiomes and host genomes.

    Science.gov (United States)

    Zhu, Lifeng; Wu, Qi; Deng, Cao; Zhang, Mengjie; Zhang, Chenglin; Chen, Hua; Lu, Guoqing; Wei, Fuwen

    2018-05-01

    Carnivorous members of the Carnivora reside at the apex of food chains and consume meat-only diets, rich in purine, fats and protein. Here, we aimed to identify potential adaptive evolutionary signatures compatible with high purine and fat metabolism based on analysis of host genomes and symbiotic gut microbial metagenomes. We found that the gut microbiomes of carnivorous Carnivora (e.g., Felidae, Canidae) clustered in the same clade, and other clades comprised omnivorous and herbivorous Carnivora (e.g., badgers, bears and pandas). The relative proportions of genes encoding enzymes involved in uric acid degradation were higher in the gut microbiomes of meat-eating carnivorans than plant-eating species. Adaptive amino acid substitutions in two enzymes, carnitine O-palmitoyltransferase 1 (CPT1A) and lipase F (LIPF), which play a role in fat digestion, were identified in Felidae-Candidae species. Carnivorous carnivorans appear to endure diets high in purines and fats via gut microbiomic and genomic adaptations. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica: estudo preliminar Oral supplementation of L-carnitine combined with exercise and respiratory training in patients with chronic obstructive pulmonary disease: preliminary study

    Directory of Open Access Journals (Sweden)

    Matheus Guedes Fernandes Silva

    2012-12-01

    Full Text Available Avaliar os efeitos da suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica (DPOC. Participaram 14 voluntários com idade de 65±10,4 anos e diagnóstico clínico de DPOC moderado, classificados de acordo com a espirometria prévia. Os voluntários foram divididos em grupo treino esteira (GTE e grupo treino muscular respiratório (GTMR. Realizaram o teste de caminhada de seis minutos (TC6', teste de caminhada com carga progressiva (TCP, avaliação nutricional do índice de massa corpórea (IMC, dose diária recomendada de L-carnitina, pressões inspiratórias (PImáx e expiratórias máximas (PEmáx. Fizeram 30 min de caminhada em esteira, 3 vezes/semana por 10 semanas, e o GTMR realizou, ainda, 10 min de treinamento muscular inspiratório (Threshold® IMT e 10 min de treinamento muscular expiratório (Threshold® PEP à 50% da PImáx e PEmáx ajustados semanalmente. Após 10 semanas, foram reavaliados. No TC6' pré e pós-programa de treinamento físico, as variáveis alteradas foram: distância percorrida (DP, frequência cardíaca (FC final, pressão arterial sistólica (PAS final, pressão arterial diastólica (PAD final e Borg final no GTMR, no GTE as variáveis alteradas foram FC repouso, FC final, PAS final, Borg repouso e DP. Comparando os grupos no TC6, o GTE apresentou FC final, PAD final e Borg final maiores do que o GTMR na reavaliação; já no TCP, a FC final, PAS final, Borg final foram maiores no GTE, e DP foi maior no GTMR. Na avaliação respiratória, a PEmáx foi maior no GTMR na reavaliação. O treino aeróbio e suplementação de L-carnitina na DPOC otimizou a performance, a capacidade física e a tolerância ao esforço.To evaluate the effects of oral supplementation of L-carnitine associated with physical and respiratory muscles training in chronic obstructive pulmonary disease (COPD. Participated 14 COPD volunteers (65±10.4 years, divided

  5. Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice.

    Science.gov (United States)

    López-Oliva, María Elvira; Garcimartin, Alba; Muñoz-Martínez, Emilia

    2017-12-01

    The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptor αβ (LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid β-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in the α-LAC-fed mice. In conclusion, 4 weeks of 14 % α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

  6. Effects of l-carnitine on oxidative stress parameters in ...

    African Journals Online (AJOL)

    Emel Peri Canbolat

    2016-08-10

    Aug 10, 2016 ... Nitric oxide (NO), malondialdehyde (MDA), total antioxidant status (TAS), total oxidative stress .... Erel's method was used for measuring TOS.19 TOS was ..... antioxidant capacity using a new generation, more stable ABTS.

  7. Effect of acetyl-L-carnitine on Vip-ergic neurons in jejunum submucous plexus of diabetic rats Efeito da acetil-L-carnitina sobre neurônios Vip-érgicos do plexo submucoso do jejuno de ratos diabéticos

    Directory of Open Access Journals (Sweden)

    Marli Aparecida Defani

    2003-12-01

    Full Text Available The effect of the treatment with acetyl-L-carnitine (ALC on neurons releasing the vasoactive intestinal polypeptide (VIP of the submucous plexus in the jejunum of diabetic rats was the purpose of our investigation. Diabetes (DM was induced by injecting streptozotocin endovenously (35mg/kg. After sacrificing the animals, the jejunum was collected and processed for VIP detection. Four groups were used: C (non-diabetic, CC (non-diabetic treated with ALC, D (diabetic, DC (diabetes treated with ALC. We analyzed the immunoreactivity and the cellular profile of 126 cell bodies. The treatment with ALC improved some aspects of DM. However, it promoted a small increase in the area of neurons from group CC, suggesting a possible neurotrophic effect. Neurons from groups D and DC showed a large increase in their cellular profile and immunoreactivity when compared to C and CC, suggesting a larger concentration of this neurotransmitter within the neurons that produce it. This observation constitutes a recurrent finding in diabetic animals, suggesting that ALC doesnot interfere in the pathophysiological mechanisms that unchain a higher production and/or neurotransmitter accumulation and increase the profile of the VIP-ergic neurons.Investigamos o efeito da acetil-L-carnitina (ALC sobre os neurônios que expressam o peptídeo intestinal vasoativo (VIP do plexo submucoso no jejuno de ratos diabéticos. O diabetes (DM foi induzido pela administração endovenosa de estreptozootocina (35mg/kg. Após o sacrifício dos animais, o jejuno foi coletado e processado para a detecção de VIP. Utilizou-se quatro grupos: C (não diabéticos, CC (não diabéticos suplementados com ALC, D (diabéticos e DC (diabéticos suplementados com ALC. Analisou-se a imunoreatividade e o perfil celular de 126 corpos celulares. O tratamento com ALC melhorou alguns aspectos do DM. Porém, promoveu pequeno aumento na área dos neurônios do grupo CC, indicando possível efeito neurotr

  8. Integrated application of transcriptomics and metabolomics provides insights into glycogen content regulation in the Pacific oyster Crassostrea gigas.

    Science.gov (United States)

    Li, Busu; Song, Kai; Meng, Jie; Li, Li; Zhang, Guofan

    2017-09-11

    The Pacific oyster Crassostrea gigas is an important marine fishery resource, which contains high levels of glycogen that contributes to the flavor and the quality of the oyster. However, little is known about the molecular and chemical mechanisms underlying glycogen content differences in Pacific oysters. Using a homogeneous cultured Pacific oyster family, we explored these regulatory networks at the level of the metabolome and the transcriptome. Oysters with the highest and lowest natural glycogen content were selected for differential transcriptome and metabolome analysis. We identified 1888 differentially-expressed genes, seventy-five differentially-abundant metabolites, which are part of twenty-seven signaling pathways that were enriched using an integrated analysis of the interaction between the differentially-expressed genes and the differentially-abundant metabolites. Based on these results, we found that a high expression of carnitine O-palmitoyltransferase 2 (CPT2), indicative of increased fatty acid degradation, is associated with a lower glycogen content. Together, a high level of expression of phosphoenolpyruvate carboxykinase (PEPCK), and high levels of glucogenic amino acids likely underlie the increased glycogen production in high-glycogen oysters. In addition, the higher levels of the glycolytic enzymes hexokinase (HK) and pyruvate kinase (PK), as well as of the TCA cycle enzymes malate dehydrogenase (MDH) and pyruvate carboxylase (PYC), imply that there is a concomitant up-regulation of energy metabolism in high-glycogen oysters. High-glycogen oysters also appeared to have an increased ability to cope with stress, since the levels of the antioxidant glutathione peroxidase enzyme 5 (GPX5) gene were also increased. Our results suggest that amino acids and free fatty acids are closely related to glycogen content in oysters. In addition, oysters with a high glycogen content have a greater energy production capacity and a greater ability to cope with

  9. Carnitine therapy for the treatment of metabolic syndrome and cardiovascular disease: evidence and controversies.

    Science.gov (United States)

    Johri, A M; Heyland, D K; Hétu, M-F; Crawford, B; Spence, J D

    2014-08-01

    As the incidence of metabolic syndrome increases, there is also a growing interest in finding safe and inexpensive treatments to help lower associated risk factors. L-carntine, a natural dietary supplement with the potential to ameliorate atherosclerosis, has been the subject of recent investigation and controversy. A majority of studies have shown benefit of L-C supplementation in the metabolic syndrome or cardiovascular risk factors. However, recent work has suggested that dietary L-C may accelerate atherosclerosis via gut microbiota metabolites, complicating the role of L-C supplementation in health. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. l-Carnitine ameliorates knee lesions in mono-iodoacetate induced ...

    African Journals Online (AJOL)

    Samia Mohamed Ali

    2016-03-28

    Mar 28, 2016 ... nonessential amino acid derivative that plays a critical role in energy production. ... and possibly increasing the risk of developing diabetes.16. Unilateral ..... may cause alteration in glucose metabolism.36. In conclusion ...

  11. Curative role of lactulose, L-carnitine, alpha-lipoic acid and ...

    African Journals Online (AJOL)

    levels of inflammatory markers were assessed in serum, liver and brain. Results: A ... stress, Cirrhosis, Acute liver injury. Tropical ... injury model and it has been widely studied in rats and in ... The animals received a standard pellet diet and.

  12. Effects of L-carnitine pretreatment in methamphetamine and 3-nitropropionic acid-induced neurotoxicity.

    Science.gov (United States)

    Binienda, Zbigniew K; Przybyla, Beata D; Robinson, Bonnie L; Salem, Nadia; Virmani, Ashraf; Amato, Antonino; Ali, Syed F

    2006-08-01

    Adult, male Sprague-Dawley rats were injected with 3-ni-tropropionic acid (3-NPA) at 30 mg/kg or methamphetamine (METH) at 20 mg/kg alone or following pretreatment with L-cartnitine (LC) at 100 mg/kg. Rectal temperature was measured before and 4 h following treatment. Animals were sacrificed at 4 h posttreatment. Monoamine neurotransmitters, dopamine (DA) and serotonin (5-HT), and their metabolites were analyzed in the striatum using high-performance liquid chromatography method coupled with electrochemical detection (HPLC/ED). Transcripts of several genes related to DA metabolism were quantified using real time reverse transciption polymerase chain reaction (RT-PCR). Core temperature decreased significantly after 3-NPA acid and increased in METH-treated rats (P protection against METH toxicity.

  13. Environmental enteric dysfunction is associated with carnitine deficiency and altered fatty acid oxidation

    Science.gov (United States)

    Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. We measured serum metabolite...

  14. Safety Measures of L-Carnitine L-Tartrate Supplementation in Healthy Men.

    Science.gov (United States)

    Rubin, Martyn R.; Volek, Jeff S.; Gomez, Ana L.; Ratamess, Nicholas A.; French, Duncan N.; Sharman, Matthew J.; Kraemer, William J.

    2001-01-01

    Examined the effects of ingesting the dietary supplement L- CARNIPURE on liver and renal function and blood hematology among healthy men. Analysis of blood samples indicated that there were no statistically significant differences between the L-CARNIPURE and placebo conditions for any variables examined, suggesting there are no safety concerns…

  15. The effects of L-carnitin in Budd-Chiari syndrome in a domestic cat

    OpenAIRE

    Aliye Sağkan Öztürk; Nuri Altuğ; Serkan İrfan Köse; Oktay Hasan Öztürk

    2016-01-01

    This paper describes a thrombosis in the vena cava caudalis of a 15 year-old cat with ascites. Trauma and eventually feline enteric corona virus infection in the cat were not detected. In the intrahepatic region, a blockage of vena cava caudalis was brought to light by ultrasonographic imaging. An aspirate of abdominal fl uid revealed modified transudate. Liver enzyme levels were increased in the serum sample of the cat. The levels of total oxidant status (TOS) and total antioxidant status (T...

  16. Perinatal upregulation of intestinal transport of carnitine (C) in newborn pigs

    International Nuclear Information System (INIS)

    Li, B.U.K.; Murray, R.D.; Heitlinger, L.A.; McClung, H.J.; Hughes, A.M.; O'Dorisio, T.M.; Sloan, H.R.

    1990-01-01

    Since C facilitates the perinatal transition from carbohydrate to lipid-derived energy, the authors examined the contribution of intestinal transport of dietary C to this process by determining [C]'s in sow's milk, pig jejunum and liver, and C flux across the jejunum (J m-s ) as a function of postnatal age. The authors measured portal venous glucagon [G] and insulin [l] as potential regulatory signals and attempted to alter intestinal transport of C by infusing G. Pigs at days 1-7 (NB-newborn), 14-16 (SU-suckling) and 33-35 (WN-weanling) were studied. [C]'s in sow milk, piglet jejunum, and liver were determined. Fluxes were measured in an Ussing chamber and in an in situ recirculating jejunal perfusion. The effect of an IV infusion of G on [ 3 H]C absorption was evaluated in a single animal; an adjacent jejunal segment received saline. Sow's milk and liver [C]'s, and jejunal C transport were highest following birth and declined towards weaning. Plasma [G] and the G:I ratio demonstrated a parallel temporal pattern. The G-stimulated jejunal segment removed 53% of the C and the non-stimulated control segment, 8%. It was concluded that during the perinatal metabolic transition, enhanced intestinal nutrient assimilation promotes the transfer of dietary C to the liver where it could facilitate fatty acid oxidation. This pattern of upregulated intestinal transport immediately after birth may be mediated by pancreatic G and I secretion

  17. Curative role of lactulose, L-carnitine, alpha-lipoic acid and ...

    African Journals Online (AJOL)

    All rights reserved. Available online at ... levels of inflammatory markers were assessed in serum, liver and brain. Results: A ... of developing overt encephalopathy. Recently, it ... and left untreated for 3 months (TAA 3 months). Group (5): rats ...

  18. CoQ10 and L-carnitine for statin myalgia?

    Science.gov (United States)

    DiNicolantonio, James J

    2012-10-01

    Statins are a standard of care in many clinical settings such as acute myocardial infarction and for patients having or at risk of cardiovascular (CV) disease. This is based on a plethora of data showing reductions in CV events and mortality. The CV benefit of statins can be partly explained by their ability to inhibit of HMG-CoA reductase, which subsequently lowers cholesterol and decreases the formation of mevalonate. However, the inhibition of the mevalonate pathway decreases the formation of coenzyme Q10 (CoQ10) within the body. It has been a long-standing theory that statin-associated muscle pain (myalgia) is caused, or at least partly contributed by, a reduction in CoQ10 levels in muscle mitochondria. One of the main side effects of statins is myalgia, which causes the patient to either stop their statin or significantly reduce the dose of their statin. The question of whether CoQ10 can help treat statin myopathy is a common one encountered by clinicians in current day practice.

  19. Analytical standards for the measurement of nutrients in infant formula : macronutrients, minerals, carnitine, taurine and nucleotides

    NARCIS (Netherlands)

    Capuano, E.; Alewijn, M.; Ruth, van S.M.; Verkaik-Kloosterman, J.

    2012-01-01

    Adequate methods with known performance characteristics for the assessment of the concentration of nutrients in infant and follow-on formula (referred to as "formula") are essential in the evaluation whether the composition deviates from the compositional provisions as laid down by law. Many

  20. R- –Lipoic acid and acetyl-L-carnitine optimal combinations in MPP ...

    African Journals Online (AJOL)

    Mitochondrial insufficiency and oxidative damage contribute to the etiopathology of Parkinson's disease (PD). However, there is a dearth of information on the protective activities against PD of mitochondrial nutrients, safe for coenzyme Q10. In the present study, the PD protective effects of two mitochondrial nutrients, ...

  1. Curative role of lactulose, L-carnitine, alpha-lipoic acid and ...

    African Journals Online (AJOL)

    Treatment with antioxidants for 3 months significantly (p < 0.05) decreased Malondialdehyde (MDA) and nitric oxide (NO) while antioxidant enzyme activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly increased (p < 0.05) in liver and brain tissues. The expressions of serum tumor ...

  2. The effect of L-carnitine on carbonic anhydrase level in rats exposed ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... effects of dantrolene on carbonic anhydrase enzyme activities. Biol. Pharm. Bull. 27: 613-616. Gülçin I, Küfrevioğlu Öİ, Oktay M (2005). Purification and characterization of polyphenol oxidase from nettle (Urtica dioica L.) and inhibition effects of some chemicals on the enzyme activity. J. Enzym. Inhib. Med.

  3. Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Cahová, M.; Chrastina, P.; Hansíková, H.; Drahota, Zdeněk; Trnovská, J.; Škop, V.; Spáčilová, J.; Malínská, H.; Oliyarnyk, O.; Papáčková, Z.; Páleníčková, E.; Kazdová, L.

    2015-01-01

    Roč. 40, č. 3 (2015), s. 280-291 ISSN 1715-5312 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : metabolic syndrome * insulin resistance * antioxidant * liver steatosis * mass spectrometry Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.910, year: 2015

  4. Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Roepstorff, Carsten; Halberg, Nils; Hillig, Thore

    2005-01-01

    Intracellular mechanisms regulating fat oxidation were investigated in human skeletal muscle during exercise. Eight young, healthy, moderately trained men performed bicycle exercise (60 min, 65% peak O2 consumption) on two occasions, where they ingested either 1) a high-carbohydrate diet (H-CHO) ...

  5. ORF Alignment: NC_002945 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ... ATP-BINDING PROTEIN ABC...TECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ... ...CAA18080.1| POSSIBLE OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE...osis H37Rv] emb|CAD95970.1| POSSIBLE ... OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE

  6. ORF Alignment: NC_002755 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ... ATP-BINDING PROTEIN ABC...TECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ... ...CAA18080.1| POSSIBLE OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE...osis H37Rv] emb|CAD95970.1| POSSIBLE ... OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE

  7. ORF Alignment: NC_000962 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ... ATP-BINDING PROTEIN ABC...TECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ... ...CAA18080.1| POSSIBLE OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE...osis H37Rv] emb|CAD95970.1| POSSIBLE ... OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE

  8. L-carnitine and contribution to normal lipid metabolism: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2018-01-01

    Following an application from Lonza Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scien......Following an application from Lonza Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion...

  9. Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

    Science.gov (United States)

    2014-12-29

    Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  10. How the mitochondrion was shaped by radical differences in substrates: what carnitine shuttles and uncoupling tell us about mitochondrial evolution in response to ROS

    NARCIS (Netherlands)

    Speijer, Dave

    2014-01-01

    As free-living organisms, alpha-proteobacteria produce reactive oxygen species (ROS) that diffuse into the surroundings; once constrained inside the archaeal ancestor of eukaryotes, however, ROS production presented evolutionary pressures - especially because the alpha-proteobacterial symbiont made

  11. The 625G>A SCAD gene variant is common but not associated with increased C4-carnitine in newborn blood spots

    NARCIS (Netherlands)

    van Maldegem, B. T.; Waterham, H. R.; Duran, M.; van der Vlies, M.; van Woerden, C. S.; Bobu, L. L.; Wanders, R. J. A.; Wijburg, F. A.

    2005-01-01

    The 625G>A variant of the short-chain acyl-CoA dehydrogenase (SCAD) gene is considered to confer susceptibility for developing 'clinical SCAD deficiency' and appears to be common in the general population. To determine the frequency of the 625G>A variant in The Netherlands, we analysed 1036

  12. ORF Alignment: NC_002755 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available TECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) BINDING LIPOPROTEIN ... PROX [Mycoba...cterium bovis AF2122/97] emb|CAD95971.1| ... POSSIBLE OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE

  13. Gclust Server: 83174 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available OTECTANT (GLYCINE BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT ATP-BINDING PROTEIN ABC TRANSPORTER PROV 1 ...nce length 376 Representative annotation POSSIBLE OSMOPROTECTANT (GLYCINE BETAINE/CARNITINE/CHOLINE/L-PROLIN

  14. ORF Alignment: NC_002945 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available TECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) BINDING LIPOPROTEIN ... PROX [Mycoba...cterium bovis AF2122/97] emb|CAD95971.1| ... POSSIBLE OSMOPROTECTANT (GLYCINE ... BETAINE/CARNITINE

  15. ORF Alignment: NC_000962 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available TECTANT (GLYCINE ... BETAINE/CARNITINE/CHOLINE/L-PROLINE) BINDING LIPOPROTEIN ... PROX [Mycoba... ... (strain H37RV) emb|CAA18081.1| POSSIBLE OSMOPROTECTANT ... (GLYCINE BETAINE/CARNITINE

  16. Download this PDF file

    African Journals Online (AJOL)

    USER

    Group IV: Rats were given carnitine (20 mg/kg bw, i.p) daily ..... It was found that, control rats showed normal histological architecture manifested by normal .... Rebouche CJ (1992): Carnitine function and requirements during the life cycle.

  17. Clinical and biochemical monitoring of patients with fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Lund, Allan Meldgaard; Skovby, Flemming; Vestergaard, Helle

    2010-01-01

    carnitine is measured to monitor carnitine supplementation in patients with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) and carnitine transporter deficiency (CTD) and to follow metabolic control and disclose deficiency states in other FAO disorders. We are evaluating long-chain acylcarnitines...

  18. Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Christensen, Mette; Olesen, Jes

    2015-01-01

    A neonate with low blood free carnitine level on newborn tandem mass spectrometry screening was evaluated for possible carnitine transporter defect (CTD). The plasma concentration of free carnitine was marginally reduced, and the concentrations of acylcarnitines (including C6, C8, and C10:1) were...

  19. Molecular regulation of fatty acid oxidation in skeletal muscle during aerobic exercise

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Fritzen, Andreas Mæchel; Kiens, Bente

    2018-01-01

    fatty acyl import, as the extent of acetyl group sequestration by carnitine determines the availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1) reaction. The rate of glycolysis seems therefore to be central to the amount of β-oxidation-derived acetyl-CoA that is oxidized...

  20. Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study

    Science.gov (United States)

    Background: Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary obj...

  1. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial

    OpenAIRE

    Badrasawi,Manal; Shahar,Suzana; Abd Manaf,Zahara; Rajab,Nor Fadilah; KAS,Devinder

    2016-01-01

    M Badrasawi,1,2 Suzana Shahar,1 AM Zahara,1 R Nor Fadilah,3 Devinder Kaur Ajit Singh4 1Dietetic Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Nutrition Program, Faulty of Applied Sciences, Palestine Polytechnic University, Hebron, Palestine; 3Biomedical Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 4Physiotherapy Programme, School of Rehabilitation Sciences, Universiti Kebangsaan Malaysia...

  2. PPARα agonists up-regulate organic cation transporters in rat liver cells

    International Nuclear Information System (INIS)

    Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

    2006-01-01

    It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

  3. Yeast Interacting Proteins Database: YML042W, YML042W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available xisomes, transfers activated acetyl groups to carnitine to form acetylcarnitine which can be shuttled across membranes...etyl groups to carnitine to form acetylcarnitine which can be shuttled across membranes Rows with this prey ...ne which can be shuttled across membranes Rows with this bait as bait Rows with this bait as bait (1) Rows w...ansfers activated acetyl groups to carnitine to form acetylcarnitine which can be shuttled across membranes

  4. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    OpenAIRE

    Lee, Jieun; Wolfgang, Michael J

    2012-01-01

    Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to...

  5. Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

    Science.gov (United States)

    Skyllouriotis, M L; Marx, M; Bittner, R E; Skyllouriotis, P; Gross, M; Wimmer, M

    1997-07-01

    We report a 20-year-old man with gigantism syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, and severe psychomotor retardation since childhood. Histochemical and biochemical analysis of skeletal muscle biopsy revealed myoadenylate deaminase deficiency; molecular genetic analysis confirmed the diagnosis of primary (inherited) myoadenylate deaminase deficiency. Plasma, urine, and muscle carnitine concentrations were reduced. L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. The combination of inherited myoadenylate deaminase deficiency, gigantism syndrome and carnitine deficiency has not previously been described.

  6. Almalki and Moselhy, Afr J Tradit Complement Altern Med. (2016) 13 ...

    African Journals Online (AJOL)

    But we will focus on the markers that has been shown to be most deregulated in diabetic rats [Hollywood et al., 2006]. L-Carnitine is an important fatty acyl carrier from cytosol to mitochondrial matrix for β oxidation. It obtained from diet (animals sources) or be synthesized from lysine and methionine. Deficiency of carnitine ...

  7. ORIGINAL ARTICLES

    African Journals Online (AJOL)

    normal humans.' As much as 50 - 60% of total carnitine in urine may be in the form of acylcarnitines. However, these proportions may vary considerably with nutritional status, exercise and disease ... utilised carnitine acetyltransferase to form a radioactive acetyl derivative from ... The calculated detection limit is. 0.2 nmol for ...

  8. ORF Alignment: NC_004310 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004310 gi|23502014 >1y7mA 26 161 48 214 1e-16 ... gb|AAL52029.1| PROBABLE CARNITINE... OPERON OXIDOREDUCTASE CAIA [Brucella melitensis ... 16M] ref|NP_539765.1| PROBABLE CARNITINE OPERON

  9. ORF Alignment: NC_003317 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003317 gi|17987131 >1y7mA 26 161 48 214 1e-16 ... gb|AAL52029.1| PROBABLE CARNITINE... OPERON OXIDOREDUCTASE CAIA [Brucella melitensis ... 16M] ref|NP_539765.1| PROBABLE CARNITINE OPERON

  10. ORF Alignment: NC_002771 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_002771 gi|15829246 >1nm8A 15 579 43 592 3e-82 ... ref|NP_326606.1| CARNITINE O-ACE...TYLTRANSFERASE [Mycoplasma pulmonis UAB CTIP] ... emb|CAC13948.1| CARNITINE O-ACETYLTRANSFERASE ...

  11. Mitochondrial dysfunction and oxidative stress in Naturally-Occurring Feline Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun

    and thiobarbituric acid reactive substances (TBARS). Results: In heart muscle of HCM cats, complex-I-linked state 3-respiration was significantly decreased (30 ± 16 pmol s -1 mg-1) compared to CON (64 ± 26 pmol s -1 mg-1) (P=0.006). Fatty acid oxidation with palmitoyl-carnitine and octanoyl-carnitine...

  12. Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite

    NARCIS (Netherlands)

    Soeters, Maarten R.; Serlie, Mireille J.; Sauerwein, Hans P.; Duran, Marinus; Ruiter, Jos P.; Kulik, Willem; Ackermans, Mariëtte T.; Minkler, Paul E.; Hoppel, Charles L.; Wanders, Ronald J. A.; Houten, Sander M.

    2012-01-01

    Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid

  13. Utilization of endogenous fatty acid stores for energy production in bovine preimplantation embryos.

    Science.gov (United States)

    Sutton-McDowall, Melanie L; Feil, Deanne; Robker, Rebecca L; Thompson, Jeremy G; Dunning, Kylie R

    2012-05-01

    Although current embryo culture media are based on carbohydrate metabolism of embryos, little is known about metabolism of endogenous lipids. L-carnitine is a β-oxidation cofactor absent in most culture media. The objective was to investigate the influence of L-carnitine supplementation on bovine embryo development. Abattoir-derived bovine cumulus oocyte complexes were cultured and fertilized. Post-fertilization, presumptive zygotes were transferred into a basic cleavage medium ± carbohydrates (glucose, lactate and pyruvate) ± 5 mm L-carnitine and cultured for 4 days in vitro. In the absence of carbohydrates during culture, embryos arrested at the 2- and 4-cell stages. Remarkably, +L-carnitine increased development to the morula stage compared to +carbohydrates alone (P levels were higher and ATP: ADP ratio were 1.9-fold lower (main effect, P < 0.05) compared to embryos cultured in -L-carnitine. Therefore, we inferred that +L-carnitine embryos were more metabolically active, with higher rates of ATP-ADP conversion. In conclusion, L-carnitine supplementation supported precompaction embryo development and there was an additive effect of +L-carnitine +carbohydrates on early embryo development, most likely through increased β-oxidation within embryos. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  14. Functional analysis of TMLH variants and definition of domains required for catalytic activity and mitochondrial targeting

    NARCIS (Netherlands)

    Monfregola, Jlenia; Cevenini, Armando; Terracciano, Antonio; van Vlies, Naomi; Arbucci, Salvatore; Wanders, Ronald J. A.; D'Urso, Michele; Vaz, Frédéric M.; Ursini, Matilde Valeria

    2005-01-01

    epsilon-N-Trimethyllysine hydroxylase (TMLH) (EC 1.14.11.8) is a non-heme-ferrous iron hydroxylase, Fe(++) and 2-oxoglutarate (2OG) dependent, catalyzing the first of four enzymatic reactions of the highly conserved carnitine biosynthetic pathway. Otherwise from all the other enzymes of carnitine

  15. Acetylcarnitine metabolism and the partial purification and characterization of an acetylcarnitine hydrolase from bovine caudal epididymal spermatozoa

    International Nuclear Information System (INIS)

    Bruns, K.A.

    1987-01-01

    Epididymal spermatozoa are capable of utilizing extracellular substrates for energy, but carbohydrates and free or esterified fatty acids are present in only very low concentrations in epididymal fluid. Acetyl-L-carnitine has been identified in epididymal fluid in low mM concentrations in several mammalian species and could possibly be an energy substrate for epididymal spermatozoa. Evidence that extracellular acetyl-L-carnitine can be used by intact caudal epididymal spermatozoa for energy, and a model for the metabolism of acetyl-L-carnitine by epididymal spermatozoa are presented here. Intact bovine and hamster caudal epididymal spermatozoa oxidized [1- 14 C] acetyl-L-carnitine to 14 CO 2 in a time-, cell number-, and substrate concentration-dependent manner. No concomitant uptake of acetyl-D,L-[N-methyl- 3 H] carnitine was observed by cells from the same preparations. Half-maximal rates of oxidation were observed at 8 mM and 4.5 mM acetyl-L-carnitine for the two species, respectively; the rates of oxidation at these concentrations were 15.3 nmol/10 8 cells·h and 2.9 nmol/10 7 cells·h. Intact spermatozoa in incubation with [ 3 H] acetyl-L-carnitine were observed to produce [ 3 H] acetate in the medium, and addition of sodium acetate competed for the uptake of radioactive acetate by these cells

  16. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.3361 >orf19.3361; Contig19-10173; 157397..>158185;... YAT2*; carnitine acetyltransferase; gene family | truncated protein MSTYRFQETLEKLPIPDLVQTCNAYLEALKPLQTEQEHE

  17. Metabolic therapy of multimorbid patients with arterial hypertension and inflammatory diseases of a parodentium

    Directory of Open Access Journals (Sweden)

    Yu. A. Sycheva

    2015-01-01

    Full Text Available AH is accompanied by deep metabolic and functional violations in organism tissue, including also the parodentium. The special attention is drawn by efficiency of the metabolic preparations possessing multimodal actions and allowing carrying out therapy of a number of states. The preparation of L-carnitine which is a perspective remedy for patients with AH associated with Inflammatory Deseased of Parodentium belongs to such means. In work studying of clinical efficiency and mechanisms action of L-carnitine in patients with AH and inflammatory diseases of parodentium was carried out. 70 patients with AH associated with IPD were divided into groups by way of simple randomization: a group with inclusion of a L-carnitine into the treatment and a control group, receiving only standard therapy. In the conducted research high antioxidant activity of the preparation is confirmed and the effect of L-carnitine normalizing tissue microcirculation is noted.

  18. Delayed onset muscle soreness: No pain, no gain? The truth behind ...

    African Journals Online (AJOL)

    Delayed onset muscle soreness (DOMS) is muscle pain and stiffness that develops ... limited success in reducing the symptoms.1,4-6 The DOMS phenomenon ... Nutritional supplementation (antioxidants and L-carnitine) shows promise, but ...

  19. Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans

    DEFF Research Database (Denmark)

    Xu, G.; Hansen, J S; Zhao, Jian-xin

    2016-01-01

    BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise...... in humans. METHODS: In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato......-splanchnic bed (n = 10). RESULTS: In the fasting state, a pronounced release of C2- and C3-carnitines from the hepato-splanchnic bed and an uptake of free carnitine by the legs were detected. Exercise further increased the release of C3-carnitine from the hepato-splanchnic bed and the uptake of free carnitine...

  20. A weak link in metabolism: the metabolic capacity for glycine ...

    Indian Academy of Sciences (India)

    Prakash

    2009-12-03

    Dec 3, 2009 ... glyoxylate, threonine and trimethyllysine (carnitine synthesis), most of them ...... Participation of glycine in porphyrin biosynthesis. Eight glycine ...... normal and streptozotocin-induced diabetic rats; J. Dent. Res. 63 23–27.

  1. Role of Erythropoietin in Renal Anemia Therapy

    African Journals Online (AJOL)

    Department of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan 453003, PR China ... on; that the use of EPO can reduce transfusion- .... accumulation of metabolites affects carnitine ... spinal cord ischemic injury.

  2. Importance of molecular diagnosis in the accurate diagnosis of ...

    Indian Academy of Sciences (India)

    1Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Yoshida Konoecho, ... of molecular diagnosis in the accurate diagnosis of systemic carnitine deficiency. .... 'affecting protein function' by SIFT.

  3. Modulation of chaperone-like and membranolytic activities of major ...

    Indian Academy of Sciences (India)

    C Sudheer Kumar

    2017-06-20

    Jun 20, 2017 ... Keywords. Capacitation; membranolytic activity; molecular chaperone; oxidative stress ... also shown to extract phospholipids from the membrane resulting ..... Gulcin I 2006 Antioxidant and antiradical activities of L-carnitine.

  4. Ablation of Steroid Receptor Coactivator-3 resembles the human CACT metabolic myopathy

    OpenAIRE

    York, Brian; Reineke, Erin L.; Sagen, Jørn V.; Nikolai, Bryan C.; Zhou, Suoling; Louet, Jean-Francois; Chopra, Atul R.; Chen, Xian; Reed, Graham; Noebels, Jeffrey; Adesina, Adekunle M.; Yu, Hui; Wong, Lee-Jun C.; Tsimelzon, Anna; Hilsenbeck, Susan

    2012-01-01

    Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypog...

  5. Measurement of urinary free and acylcarnitines: quantitative acylcarnitine profiling in normal humans and in several patients with metabolic errors

    International Nuclear Information System (INIS)

    Montgomery, J.A.; Mamer, O.A.

    1989-01-01

    A method for determining urinary concentrations of carnitine and acylcarnitine esters is described that employs fast atom bombardment mass spectrometry, stable isotope dilution techniques, and a novel deutero-methyl esterification that permits unambiguous identification and quantitation of free carnitine and acylcarnitines. It is rapid, does not require chromatographic or other isolation procedures, and is immune to analyte losses in sample preparation. Urinary concentrations are reported for adult control subjects and for others with various metabolic disorders

  6. Possible mechanism for species difference on the toxicity of pivalic acid between dogs and rats

    International Nuclear Information System (INIS)

    Yamaguchi, Toshiro; Nakajima, Yoshitsugu; Nakamura, Yutaka

    2006-01-01

    In a high dose toxicity study of pivalic acid (PA), PA caused skeletal muscle disorder in dog, and a significant increase of pivaloyl carnitine (PC) was observed in canine muscle, but not in rat muscle. In order to understand species difference of the toxicity of PA, we compared the in vitro metabolism of PA among dog, rat and rabbit, especially focussing on the carnitine conjugate. Canine muscle showed low, but significant carnitine conjugating activity, while that of rat was negligible. Canine kidney mitochondria had significant activity in the pivaloyl CoA synthesis (7 nmol/mg protein/h), but muscle mitochondria showed only trace activity. Both kidney and muscle mitochondria displayed similar carnitine acyltransferase activity (2-3 nmol/mg protein/h) towards pivaloyl CoA. On the other hand, with respect to the activity of carnitine acyltransferase in the reverse direction using PC as substrate, canine muscle mitochondria showed higher activity than that of kidney mitochondria. This means that PC is not the final stable metabolite, but is converted easily to pivaloyl CoA in canine muscle. These results suggest one of the possible mechanisms for canine selective muscle disorder to be as follows. Only canine muscle can metabolize PA to its carnitine conjugate slowly, but significantly. In canine muscle, PC is not the final stable metabolite; it is easily converted to pivaloyl CoA. As carnitine conjugation is thought to be the only detoxification metabolic route in canine muscle, under certain circumstances such as carnitine deficiency, the risk of exposure with toxic pivaloyl CoA might increase and the CoASH pool in canine muscle might be exhausted, resulting in toxicity in canine muscle

  7. Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

    Science.gov (United States)

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

    Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

    Directory of Open Access Journals (Sweden)

    Jane Alcorn

    2010-10-01

    Full Text Available Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20. Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

  9. Studies concerning chronic and acute effects of L-carnitina in elite athletes.

    Science.gov (United States)

    Drăgan, I G; Vasiliu, A; Georgescu, E; Eremia, N

    1989-01-01

    Chronic and acute effects of L-Carnitina (vials of 1 g L-Carnitina endovenous; per orally administered vials of 1 g L-Carnitina; tablets of 1 g L-Carnitina) were recorded in 110 top athletes (rowing, kayak-canoe, swimming, weightlifting medium and long-distance runners), 47 girls and 63 boys, by six double blind placebo trials and cross over. Significant changes were registered after L-Carnitina treatment (both for a single dose or after 3 weeks of treatment) compared to placebo, for FFA, triglycenides, lactic acid after exercise, evoked muscular potential, plasma carnitine (free and acetyl-carnitine), urine carnitine (free carnitine) and others. The authors explain these changes by the increase of free carnitine, which permits a larger quantity of FFA to enter the mitochondria and to be more extensively used as energy source in endurance and strength efforts. Based on these results the authors recommend L-Carnitina as an ergogenic aid in elite athletes, especially in endurance and strength sports.

  10. Sudden infant death syndrome (SIDS): a time lag factor.

    Science.gov (United States)

    Reid, G M

    1991-02-01

    A time lag factor of about five days has been identified in an increased incidence of SIDS in relation to a cold day. Sudden exposure to chilling appeared to trigger skeletal muscle weakness and renal failure about five days later in a man found to have only 25% of normal carnitine palmitoyl transferase (CPT) activity in biopsied skeletal muscle. White Muscle Disease is a muscular dystrophy in young ruminants which appears about five days after turnout to pasture in the weaned ruminant raised on a diet deficient in vitamin E and selenium (VESD). Pasture has high levels of linoleic and linolenic acid (high PUFA diet) which are modified by developing rumen bacteria. Corbucci investigated the effects of circulatory shock (cardiogenic) on skeletal muscle mitochondrial activity in humans. Cytochrome oxidase activity fell markedly and, in particular, the capacity to oxidase palmitoyl carnitine was greatly reduced. He considered a consequence of this disorder was sequestration of carnitine as acyl carnitine which could not be recycled. Unusual acyl carnitines have been identified in six out of 13 SIDS victims in a USA group. In Finland, researchers identified a rise in SIDS incidence (mostly found in the prone position) after great and rapid temperature changes. Foster found a relationship between 1984 SIDS incidence and the incidence of goitre in World War I troops.

  11. Stabilization of blood methylmalonic acid level in methylmalonic acidemia after liver transplantation.

    Science.gov (United States)

    Chen, P W; Hwu, W L; Ho, M C; Lee, N C; Chien, Y H; Ni, Y H; Lee, P H

    2010-05-01

    Methylmalonic acidemia with complete mutase deficiency (mut(0) type) is an inborn error of metabolism with high mortality and morbidity. LT has been suggested to be a solution to this disease, but elevation of urinary and blood MMA was still observed after LT. In this study, we measured dry blood spot MMA and its precursor propionyl-carnitine (C3-carnitine) for mut(0) patients. The results revealed that when C3-carnitine rose during metabolic stress, MMA rose exponentially (up to 1000 micromol/L) in patients who did not undergo LT. In patients who underwent LT, MMA rose to 100-200 micromol/L when C3-carnitine reached 10-20 micromol/L. However, when C3-carnitine rose further to 40-50 micromol/L, MMA levels just stayed put. Therefore, LT stabilized blood MMA level, though there might be a threshold for blood MMA clearance by the donor liver. This finding should be critical to understand the long-term outcome for LT in methylmalonic acidemia.

  12. Hyperammonemia Associated with Valproic Acid Concentrations

    Directory of Open Access Journals (Sweden)

    Marta Vázquez

    2014-01-01

    Full Text Available Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β-oxidation in the mitochondria one of its main metabolic route (40%. Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.

  13. Depressive state and chronic fatigue in multiple sclerosis and neuromyelitis optica.

    Science.gov (United States)

    Akaishi, Tetsuya; Nakashima, Ichiro; Misu, Tatsuro; Fujihara, Kazuo; Aoki, Masashi

    2015-06-15

    Depression and chronic fatigue are frequently present in multiple sclerosis (MS); however, the prevalence rates have not been investigated in neuromyelitis optica (NMO). Thirty-nine consecutive NMO and 75 MS patients were compared using self-rating questionnaires for depressive states, daily activity, and fatigue, as well as serum carnitine levels. A subgroup of patients with low carnitine levels were re-evaluated regarding depression and fatigue after levocarnitine treatment. Depression and fatigue were equally prevalent in MS and NMO and were strongly correlated with one another. Measurement of the serum carnitine levels and the administration of levocarnitine did not appear to be beneficial. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Clinical and biochemical monitoring of patients with fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Lund, Allan Meldgaard; Skovby, Flemming; Vestergaard, Helle

    2010-01-01

    complicated assessments by a neuropsychologist, speech therapist, or physical and occupational therapists. Paraclinical measurements are not used for short-chain and medium-chain disorders; electrocardiography (including 24 h monitoring) and echocardiography are done for most patients with long......Evidence-based guidelines for monitoring patients with disorders in fatty acid oxidation (FAO) are lacking, and most protocols are based on expert statements. Here, we describe our protocol for Danish patients. Clinical monitoring is the most important measure and has the main aims of checking...... carnitine is measured to monitor carnitine supplementation in patients with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) and carnitine transporter deficiency (CTD) and to follow metabolic control and disclose deficiency states in other FAO disorders. We are evaluating long-chain acylcarnitines...

  15. Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial.

    Science.gov (United States)

    Heianza, Yoriko; Sun, Dianjianyi; Li, Xiang; DiDonato, Joseph A; Bray, George A; Sacks, Frank M; Qi, Lu

    2018-06-02

    Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention. We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated. Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (p interaction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids. Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism. NCT00072995. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

  16. Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

    Science.gov (United States)

    2017-08-31

    Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

  17. Treatment Opportunities in Patients With Metabolic Myopathies

    DEFF Research Database (Denmark)

    Ørngreen, Mette Cathrine; Vissing, John

    2017-01-01

    the development of new therapeutic options. Enzyme replacement therapy with rGAA has revolutionized treatment of early onset Pompe disease. Supplements of riboflavin, carnitine, and sucrose show promise in patients with respectively riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, primary...... carnitine deficiency, and McArdle disease. Treatment with citric acid cycle intermediates supply by triheptanoin seems promising in patients with glucogenoses, and studies are ongoing in patients with McArdle disease. Summary Treatment of metabolic myopathies primarily relies on avoiding precipitating...

  18. Ovlivnění anticholinesterázové aktivity 7-methoxytacrinu a galantaminu L-karnitinem

    OpenAIRE

    Novotná, Petra

    2012-01-01

    Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of biological and medical sciences Candidate: Mgr. Petra Novotná Consultant: doc. MUDr. J. Herink, DrSc. Title of Thesis: The influencing of anticholinesterase activity of 7-methoxytacrine and galantamine by L-carnitine The aim of this work was to test the ability of L-carnitine (KAR) to increase the permeation of indirect parasympatomimetic 7-methoxytacrine (MEOTA) and galantamine (GAL) through the blood-brain barr...

  19. Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome

    NARCIS (Netherlands)

    Schreurs, M.; Kuipers, F.; van der Leij, F. R.

    P>Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate-activated protein kinase. Carnitine palmitoyltransferase 1 (CPT1) controls mitochondrial beta-oxidation and is inhibited by malonyl-CoA, the product of acetyl-CoA carboxylase (ACC). The adenosine

  20. Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT

    NARCIS (Netherlands)

    Schulze, Sabrina; Köster, Stefan; Geldmacher, Ulrike; Terwisscha van Scheltinga, Anke C.; Kühlbrandt, Werner

    2010-01-01

    Transport of solutes across biological membranes is performed by specialized secondary transport proteins in the lipid bilayer, and is essential for life. Here we report the structures of the sodium-independent carnitine/butyrobetaine antiporter CaiT from Proteus mirabilis (PmCaiT) at 2.3-Å and from

  1. Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity

    DEFF Research Database (Denmark)

    Kraunsøe, Regitze; Boushel, Robert Christopher; Hansen, Christina Neigaard

    2010-01-01

    were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled...

  2. 77 FR 38204 - Cyflufenamid; Pesticide Tolerances

    Science.gov (United States)

    2012-06-27

    ... data supporting the petition, EPA has slightly increased the tolerances for pome fruit (Crop Group 11... information in support of this action. EPA has sufficient data to assess the hazards of and to make a... decreased lipid metabolism; cyflufenamid caused an approximately 50% inhibition of carnitine...

  3. Karnitintransporterdefekt er en arvelig sygdom med høj hyppighed på Færøerne

    DEFF Research Database (Denmark)

    Poulsen, Sissal Djurhuus; Lund, Allan Meldgaard; Christensen, Ernst

    2012-01-01

    The Faroe Islands has a high incidence of carnitine transporter deficiency (CTD) and several other autosomal recessive diseases. This article describes the reason for the high frequency, in view of the Faroese history and the diagnosis of CTD. Few individuals founded the Faroese population in the 9...

  4. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences. C SUDHEER KUMAR. Articles written in Journal of Biosciences. Volume 42 Issue 3 September 2017 pp 469-479 Article. Modulation of chaperone-like and membranolytic activities of major horse seminal plasma protein HSP-1/2 by L-carnitine · C SUDHEER KUMAR MUSTI J ...

  5. Karnitintransporterdefekt er en arvelig sygdom med høj hyppighed på Færøerne

    DEFF Research Database (Denmark)

    Poulsen, Sissal Djurhuus; Lund, Allan Meldgaard; Christensen, Ernst

    2012-01-01

    The Faroe Islands has a high incidence of carnitine transporter deficiency (CTD) and several other autosomal recessive diseases. This article describes the reason for the high frequency, in view of the Faroese history and the diagnosis of CTD. Few individuals founded the Faroese population in the 9......th century, and subsequent geographic isolation limited genetic diversity in the Islands....

  6. Control of bovine hepatic fatty acid oxidation

    International Nuclear Information System (INIS)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-01-01

    Fatty acid oxidation by bovine liver slices and mitochondria was examined to determine potential regulatory sites of fatty acid oxidation. Conversion of 1-[ 14 C]palmitate to 14 CO 2 and total [ 14 C]acid-soluble metabolites was used to measure fatty acid oxidation. Oxidation of palmitate (1 mM) was linear in both liver slice weight and incubation time. Carnitine stimulated palmitate oxidation; 2 mM dl-carnitine produced maximal stimulation of palmitate oxidation to both CO 2 and acid-soluble metabolites. Propionate (10 mM) inhibited palmitate oxidation by bovine liver slices. Propionate (.5 to 10 mM) had no effect on palmitate oxidation by mitochondria, but malonyl Coenzyme A, the first committed intermediate of fatty acid synthesis, inhibited mitochondrial palmitate oxidation (inhibition constant = .3 μM). Liver mitochonndrial carnitine palmitoyltransferase exhibited Michaelis constants for palmitoyl Coenzyme A and l-carnitine of 11.5 μM and .59 mM, respectively. Long-chain fatty acid oxidation in bovine liver is regulated by mechanisms similar to those in rats but adapted to the unique digestive physiology of the bovine

  7. thalassemic children

    African Journals Online (AJOL)

    L-carnitine therapy (50mg/kg/d for at least 6 months) had significantly lower prevalence and .... to maintain their growth and 5 were oc- casionally ... 20 minutes at room temperature in the dark. ...... ing skeletal muscle myopathy in heart failure.

  8. Sites of reactive oxygen species generation by mitochondria oxidizing different substrates

    DEFF Research Database (Denmark)

    Quinlan, Casey L; Perevoshchikova, IrinaV; Hey-Mogensen, Martin

    2013-01-01

    a variety of conventional substrates in the absence of added inhibitors: succinate; glycerol 3-phosphate; palmitoylcarnitine plus carnitine; or glutamate plus malate. In all cases, the sum of the estimated rates accounted fully for the measured overall rates. There were two striking results. First...

  9. Sequence Classification: 400201 [

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT INTEGRAL MEMBRANE PROTEIN ABC TRANSPORTER PROZ || http://www.ncbi.nlm.nih.gov/protein/15610892 ... ...Non-TMB TMH Non-TMB TMB TMB Non-TMB >gi|15610892|ref|NP_218273.1| POSSIBLE OSMOPROT

  10. Metabolic changes during treatment with valproate in humans: Implication for untoward weight gain

    DEFF Research Database (Denmark)

    Breum, L.; Astrup, A.; Gram, L.

    1992-01-01

    of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance....

  11. Sequence Classification: 390416 [

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT INTEGRAL MEMBRANE PROTEIN ABC TRANSPORTER PROW || http://www.ncbi.nlm.nih.gov/protein/31794927 ... ...Non-TMB TMH Non-TMB TMB TMB Non-TMB >gi|31794927|ref|NP_857420.1| POSSIBLE OSMOPROT

  12. beta-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E(2) synthesis in rat hepatocytes-Kupffer cells

    DEFF Research Database (Denmark)

    Du, Zhen-Yu; Ma, Tao; Winterthun, Synnøve

    2010-01-01

    and eicosapentaenoic acid (EPA) for PGE(2) synthesis in a rat hepatocyte-Kupffer cell (HPC/KC) co-culture system when the cellular oxidation capacity was enhanced by exogenous l-carnitine. We demonstrate that in the absence of l-carnitine, 1) beta-oxidation rates of EPA and AA were comparable in HPCs and in KCs; 2) AA...... and not EPA was preferentially incorporated into glycerolipids; and 3) addition of EPA significantly decreased AA-dependent PGE(2) synthesis in HPCs and cyclooxygenase-2 (COX-2) expression in co-cultured HPCs/KCs. However, enhancing the cellular oxidation capacity by the addition of l-carnitine 1...... inhibition of AA-dependent PGE(2) synthesis and COX-2 expression by EPA. Taken together, the results strongly suggest that l-carnitine affects competition between AA and EPA in PG synthesis in liver cells by enhancing oxidation of EPA in HPCs. This implies that the beneficial effects of n-3 PUFA, especially...

  13. 4-cyano-3-hydroxybutanoyl hydrazines, derivatives and process for the preparation thereof

    Energy Technology Data Exchange (ETDEWEB)

    Hollingsworth, Rawle I. (Haslett, MI); Wang, Guijun (East Lansing, MI)

    2000-01-01

    Novel 4-cyano-3-hydroxybutanoyl hydrazides (10), particularly R-chiral intermediates are described. The intermediates are useful in preparing (R)-3-hydroxy-4-trimethylaminobutyric acid (L-carnitine) and R-4-amino-3-hydroxybutyric acid (GABOB) and chiral chemical intermediates which are medically useful.

  14. Sequence Classification: 390415 [

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT INTEGRAL MEMBRANE PROTEIN ABC TRANSPORTER PROZ || http://www.ncbi.nlm.nih.gov/protein/31794926 ... ...Non-TMB TMH Non-TMB TMB TMB Non-TMB >gi|31794926|ref|NP_857419.1| POSSIBLE OSMOPROT

  15. Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase

    DEFF Research Database (Denmark)

    Chen, Yun; Zhang, Yiming; Siewers, Verena

    2015-01-01

    Saccharomyces cerevisiae, acetyl-CoA is compartmentalized in the cytosol, mitochondrion, peroxisome and nucleus, and cannot be directly transported between these compartments. With the acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the cytoplasm can be transported...

  16. Sequence Classification: 400202 [

    Lifescience Database Archive (English)

    Full Text Available ECTANT (GLYCINE BETAINE/CARNITINE/CHOLINE/L-PROLINE) TRANSPORT INTEGRAL MEMBRANE PROTEIN ABC TRANSPORTER PROW || http://www.ncbi.nlm.nih.gov/protein/15610893 ... ...Non-TMB TMH Non-TMB TMB TMB Non-TMB >gi|15610893|ref|NP_218274.1| POSSIBLE OSMOPROT

  17. Clinical aspects of short-chain acyl-CoA dehydrogenase deficiency

    NARCIS (Netherlands)

    Maldegem, B.T.; Wanders, R.J.A.; Wijburg, F.A.

    2010-01-01

    Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation. SCADD is biochemically characterized by increased C4-carnitine in plasma and ethylmalonic acid in urine. The diagnosis of SCADD is confirmed by DNA analysis showing

  18. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    We carried out extensive simulation studies to assess the proposed method. ... transmission dynamics and life history characteristics in parasite populations .... A novel missense mutation in collagenous domain of EDA gene in a ... Importance of molecular diagnosis in the accurate diagnosis of systemic carnitine deficiency.

  19. Mechanism of Osmotic Activation of the Quaternary Ammonium Compound Transporter (QacT) of Lactobacillus plantarum

    NARCIS (Netherlands)

    Glaasker, Erwin; Heuberger, Esther H.M.L.; Konings, Wil N.; Poolman, Bert

    1998-01-01

    The accumulation of quaternary ammonium compounds in Lactobacillus plantarum is mediated via a single transport system with a high affinity for glycine betaine (apparent Km of 18 μM) and carnitine and a low affinity for proline (apparent Km of 950 μM) and other analogues. Mutants defective in the

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 701 - 750 of 2200 ... ... (2007), Effects of dietary energy density and L-carnitine supplementation on growth performance, carcass traits and blood parameters of broiler chickens ... Effects of dietary fish oil and flax seed on cholesterol and fatty acid composition of egg yolk and blood parameters of laying hens, Abstract PDF.

  1. Author Details

    African Journals Online (AJOL)

    Barakat, LAA. Vol 29, No 1 (2011) - Articles Effects of L-Carnitine and Taurine on associated biochemical changes in Alloxan induced diabetic rats. Abstract. ISSN: 1687-1502. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners ...

  2. Enzyme Activities in Oleaginous Yeasts Accumulating and Utilizing Exogenous or Endogenous Lipids

    NARCIS (Netherlands)

    Holdsworth, Jane E.; Veenhuis, Marten; Ratledge, Colin

    1988-01-01

    The activities of ATP:citrate lyase (ACL; EC 4.1.3.8), carnitine acetyltransferase (CAT; EC 2.3.1.7), NADP+-dependent isocitrate dehydrogenase (ICDH; EC 1.1.1.42), isocitrate lyase (ICL; EC 4.1.3.1) and malic enzyme (malate dehydrogenase; EC 1.1.1.40) were measured in four oleaginous yeasts, Candida

  3. Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as marker of SCAD defect and ethylmalonic encephalopathy

    DEFF Research Database (Denmark)

    Merinero, B; Perez-Cerda, C; Ruiz Sala, P

    2007-01-01

    High concentrations of butyryl/isobutyrylcarnitine (C(4)-carnitine) in plasma with increase of ethylmalonic acid (EMA) in urine point to different genetic entities, and further investigations are required to differentiate the possible underlying defect. Here we report three unrelated cases, two n...

  4. Almalki and Moselhy, Afr J Tradit Complement Altern Med. (2016) 13 ...

    African Journals Online (AJOL)

    Results: Treatment of diabetic rats with lutein, L-carnitine, combined ... This could be said to have justified obtaining serum as a tool for early detection of diabetes. .... and IL-1 play an important role in the pathogenesis of diabetic retinopathy.

  5. Disease: H00488 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available type and phenotype? ... JOURNAL ... Hum Mol Genet 6:695-707 (1997) DOI:10.1093/hmg/6.5.695 ... PMID:15877203 (drug) ... AUTHORS ... Lee PJ, Harr...ison EL, Jones MG, Jones S, Leonard JV, Chalmers RA ... TITLE ... L-carnitine and exe

  6. Self-Assembled Core-Satellite Gold Nanoparticle Networks for Ultrasensitive Detection of Chiral Molecules by Recognition Tunneling Current.

    Science.gov (United States)

    Zhang, Yuanchao; Liu, Jingquan; Li, Da; Dai, Xing; Yan, Fuhua; Conlan, Xavier A; Zhou, Ruhong; Barrow, Colin J; He, Jin; Wang, Xin; Yang, Wenrong

    2016-05-24

    Chirality sensing is a very challenging task. Here, we report a method for ultrasensitive detection of chiral molecule l/d-carnitine based on changes in the recognition tunneling current across self-assembled core-satellite gold nanoparticle (GNP) networks. The recognition tunneling technique has been demonstrated to work at the single molecule level where the binding between the reader molecules and the analytes in a nanojunction. This process was observed to generate a unique and sensitive change in tunneling current, which can be used to identify the analytes of interest. The molecular recognition mechanism between amino acid l-cysteine and l/d-carnitine has been studied with the aid of SERS. The different binding strength between homo- or heterochiral pairs can be effectively probed by the copper ion replacement fracture. The device resistance was measured before and after the sequential exposures to l/d-carnitine and copper ions. The normalized resistance change was found to be extremely sensitive to the chirality of carnitine molecule. The results suggested that a GNP networks device optimized for recognition tunneling was successfully built and that such a device can be used for ultrasensitive detection of chiral molecules.

  7. [Primary trimethylaminuria: the fish odor syndrome

    NARCIS (Netherlands)

    Montoya Alvarez, T.; Guardiola, P.; Roldan, J.O.; Elviro, R.; Wevers, R.A.; Guijarro, G.

    2009-01-01

    Primary trimethylaminuria, or fish odor syndrome, is a congenital metabolic disorder characterized by a failure in the hepatic trimethylamine (TMA) oxidation route to trimethylamine N-oxide (TMANO). TMA is mostly derived from dietary precursors such as choline, carnitine and TMANO. The presence of

  8. [Intraoperative lactic acidosis, can it be treated? Clinico-experimental, prospective, sequential study].

    Science.gov (United States)

    Pietropaoli, P; Caporelli, S; De Pace, F; Donati, A; Adrario, E; Luzi, A; Munch, C; Giovannini, C; Frezzotti, A R

    1994-12-01

    To verify the efficacy and absence of risk attributable to therapy with alkaline solutions for correction of lactic acidosis and to demonstrate the usefulness of L-carnitine in converting lactate into pyruvate in conditions of good blood oxygenation. Prospective study on a consecutive series of patients subdivided into three groups following the use of: alkalinizing therapy (group I), L-carnitine (group II), or saline solution (group III). Groups 1 and 2 were further subdivided into subgroups "a" and "b" according to the type of alkalinizing agent and of L-carnitine somministration. Teaching Hospital-Torrette di Ancona. 65 patients submitted to major vascular surgery with aortic clamping in the time period between January 1992 and August 1993. During aortic clamping patients of: group I received 2 mEq:kg of bicarbonate or tromentamolo according to the specific subgroup. Group II received a bolus of 2 g of L-carnitine, patients of group IIb received further 2 g of carnitine in continuous perfusion until the end of surgery. Group III received no pharmacological intervention. HR BP, arterial blood gases and lactic acid levels were measured at 12 pre-determined times. Only a neutralizing effect of alkalinizing therapy was observed, whereas the lactic acid measurements demonstrated no significant differences between the different groups. These results confirm the data of other Authors concerning the good compliance of alkalinizing therapy, however, there was demonstrated no clear evidence of its effective usefulness. No metabolic stimulation due to L-canitina could be demonstrated in our experimental conditions.

  9. Efficacy of osmoprotectants on prevention and treatment of murine dry eye.

    Science.gov (United States)

    Chen, Wei; Zhang, Xin; Li, Jinyang; Wang, Yu; Chen, Qi; Hou, Chao; Garrett, Qian

    2013-09-19

    To evaluate the efficacy of osmoprotectants on prevention and treatment of dry eye in a murine model. Dry eye was induced in mice by using an intelligently controlled environmental system (ICES). Osmoprotectants betaine, L-carnitine, erythritol, or vehicle (PBS) were topically administered to eyes four times daily following two schedules: schedule 1 (modeling prevention): dosing started at the beginning of housing in ICES and lasted for 21 or 35 days; schedule 2 (modeling treatment): dosing started after ICES-housed mice developed dry eye (day 21), continuing until day 35. Treatment efficacy was evaluated for corneal fluorescein staining; corneal epithelial apoptosis by TUNEL and caspase-3 assays; goblet cell numbers by PAS staining; and expression of inflammatory mediators, TNF-α, IL-17, IL-6, or IL-1β by using RT-PCR on days 0, 14, 21, and/or 35. Compared with vehicle, prophylactic administration of betaine, L-carnitine, or erythritol significantly decreased corneal staining and expression of TNF-α and IL-17 on day 21 (schedule 1). Treatment of mouse dry eye with osmoprotectants significantly reduced corneal staining on day 35 compared with day 21 (schedule 2). Relative to vehicle, L-carnitine treatment of mouse dry eye for 14 days (days 21 to 35) resulted in a significant reduction in corneal staining, number of TUNEL-positive cells, and expression of TNF-α, IL-17, IL-6, or IL-1β, as well as significantly increased the number of goblet cells. Topical application of betaine, L-carnitine, or erythritol systematically limited progression of environmentally induced dry eye. L-carnitine can also reduce the severity of such dry-eye conditions.

  10. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism.

    Science.gov (United States)

    Lee, Jieun; Wolfgang, Michael J

    2012-10-25

    Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT) and CPT1c knockout (KO) mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  11. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jieun

    2012-10-01

    Full Text Available Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. Results In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT and CPT1c knockout (KO mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Conclusions Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  12. [SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome: a case report and review of literature].

    Science.gov (United States)

    Liu, Zhimei; Fang, Fang; Ding, Changhong; Wu, Husheng; Lyu, Junlan; Wu, Yun

    2014-11-01

    To analyze the clinical characteristics of SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome (MDS) in one patient, and review the latest clinical research reports. Clinical, laboratory and genetic data of one case of SUCLA2-related encephalomyopathic MDS diagnosed by department of Neurology, Beijing Children's Hospital in November, 2013 were reported, and through taking "SUCLA2" as key words to search at CNKI, Wanfang, PubMed and the Human Gene Mutation Database (HGMD) professional to date, the clinical characteristics of 24 reported cases of SUCLA2-related encephalomyopathic MDS in international literature in combination with our case were analyzed. (1) The patient was 5 years and 9 months old, born as a term small for gestational age infant whose birth weight was 2 400 g, and presented since birth with severe muscular hypotonia, feeding difficulties, failure to thrive, psychomotor retardation and hearing impairment. Until now, he still showed severe developmental retardation, together with muscular atrophy, thoracocyllosis and scoliosis, and facial features. The patient is the first born from consanguineous healthy parents, whose relationship is cousins. Laboratory tests showed urinary excretion of mild methylmalonic acid (MMA), elevated plasma lactate concentration, and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling. MRI showed brain atrophy-like and bilateral T2 hyperintensities in bilateral caudate nuclei and putamen. By Next-Generation Sequencing (NGS), we identified a novel homozygous missense mutation (c.970G > A) in the SUCLA2 in a highly conserved amino acid residue. (2) The total number was only 25 with a male to female ratio of 14: 11, and age of onset of 23 was 0-4 months. The most common clinical features in patients with SUCLA2 mutation were permanent hypotonia, muscle atrophy, psychomotor retardation and scoliosis or kyphosis. Frequent signs included hearing impairment, hyperkinesia

  13. Metabolomic Changes During the 18-Month Copenhagen Insulin and Metformin Therapy (CIMT) Trial

    DEFF Research Database (Denmark)

    Suvitaival, Tommi; Safai, Narges; Ali, Ashfaq

    decrease in glycerophosphocholine between baseline and follow-up when compared to placebo (Figure). The placebo group had a broad increase in amino acids and their derivatives as well as in acyl-carnitines, lipids, other metabolites, LDL and BMI, and clear changes in branched-chain amino acids. Nearly all...... spectrometer, uncovering relative levels of amino acids, acyl-carnitines, lipids and other metabolites.  Standardized data consisting of the metabolites, clinical variables and laboratory measurements were analyzed with a two-way repeated measures ANOVA model inferred with a linear mixed effects model in R...... of these increases were smaller or not seen in the metformin group. The results indicate that metformin helped maintain a better glucose control, which was broadly reflected in the levels of amino acids and lipids....

  14. Lipid storage myopathy with clinical markers of Marfan syndrome: A rare association

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    Subasree Ramakrishnan

    2012-01-01

    Full Text Available Disorders of lipid metabolism can cause variable clinical presentations, often involving skeletal muscle, alone or together with other tissues. A 19-year-old boy presented with a 2-year history of muscle pain, cramps, exercise intolerance and progressive weakness of proximal lower limbs. Examination revealed skeletal markers of Marfan syndrome in the form of increased arm span compared with height, Kyphoscoliois, moderate pectus excavatum, high arched palate and wrist sign. He also had mild neck flexor weakness and proximal lower limb weakness with areflexia. Pathologic findings revealed lipid-laden fine vacuoles in the muscle fibers. Possibility of carnitine deficiency myopathy was considered and the patient was started on carnitine and Co Q. The patient made remarkable clinical improvement over the next 2 months. This case is reported for rarity of the association of clinical markers of Marfan syndrome and lipid storage myopathy and sparse literature on lipid storage myopathy in the Indian context.

  15. Screening of a healthy newborn identifies three adult family members with symptomatic glutaric aciduria type I

    Directory of Open Access Journals (Sweden)

    MCH Janssen

    2014-06-01

    Full Text Available We report three adult sibs (one female, two males with symptomatic glutaric acidura type I, who were diagnosed after a low carnitine level was found by newborn screening in a healthy newborn of the women. All three adults had low plasma carnitine, elevated glutaric acid levels and pronounced 3-hydroxyglutaric aciduria. The diagnosis was confirmed by undetectable glutaryl-CoA dehydrogenase activity in lymphocytes and two pathogenic heterozygous mutations in the GCDH gene (c.1060A>G, c.1154C>T. These results reinforce the notion that abnormal metabolite levels in newborns may lead to the diagnosis of adult metabolic disease in the mother and potentially other family members.

  16. Refractory Hyperlactatemia with Organ Insufficiency in Lipid Storage Myopathy.

    Science.gov (United States)

    Xu, Yuanda; Zhou, Li; Liang, Weibo; He, Weiqun; Liu, Xiaoqing; Liang, Xiuling; Zhong, Nanshan; Li, Yimin

    2015-08-01

    Lipid storage myopathy is a metabolic disorder characterized by abnormal lipid accumulation in muscle fibers and progressive muscle weakness. Here, we report the case of a 17-year-old woman with progressive muscle weakness, refractory hyperlactatemia, and multiple organ insufficiency. Severe pneumonia was the initial diagnosis. After anti-infective treatment, fluid resuscitation, and mechanical ventilation, the patient's symptoms improved but hyperlactatemia and muscle weakness persisted. She was empirically treated with carnitine. Biochemical tests, electromyography, and muscle biopsy confirmed lipid storage myopathy. After 7 weeks of treatment, the patient resumed normal daily life. An empirical treatment with carnitine may be beneficial for patients before an accurate diagnosis of lipid storage myopathy is made.

  17. L-acetylcarnitine enhances functional muscle re-innervation.

    Science.gov (United States)

    Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

    1991-01-01

    The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

  18. Metabolomic profiles of colostrum and milk from lactating sows

    DEFF Research Database (Denmark)

    Curtasu, Mihai Victor; Theil, Peter Kappel; Hedemann, Mette Skou

    2016-01-01

    Survival and growth of sucklingpiglets is highly dependent on the nutrients, growthfactors, and protective components provided bysow colostrum and milk. The macrochemical compositionundergoes large alterations during thelactation period, but knowledge of the compositionand variation of low...... molecular weight metabolitesis presently lacking. Samples of colostrum at 0, 12,24, and 36 h and milk samples on Day 3, 10, 17,and 24 relative to farrowing were collected from 4s parity sows fed a standard lactation diet. Sampleswere analyzed using a nontargeted metabolomicsapproach. Sample preparation...... and the variablesresponsible for separation. PCA revealed data clusteringaccording to sample type, with differencesobserved between colostrum and milk for both ionizationmodes. Positive ionization revealed a numberof highly influential metabolites, such as l-carnitine,acyl esters of carnitine (l-acetylcarnitine, 2...

  19. Testicular torsion

    DEFF Research Database (Denmark)

    Brasso, K; Andersen, L; Kay, L

    1993-01-01

    Thirty-five patients were examined 6-11 years after operation for torsion of the testis. Loss of testicular tissue was significantly associated with long preoperative duration of symptoms and with low postoperative sperm counts. The sex hormones were normal in the majority of patients...... to the sperm count and concentration. Measurement of carnitine levels in seminal plasma, as a sign of vas deferens obstruction or dysfunction of epididymis, and of autoantibodies against spermatozoa revealed no significant findings....

  20. Evidence for marsh mallow (Malva parviflora) toxicosis causing myocardial disease and myopathy in four horses.

    Science.gov (United States)

    Bauquier, J; Stent, A; Gibney, J; Jerrett, I; White, J; Tennent-Brown, B; Pearce, A; Pitt, J

    2017-05-01

    Investigation of toxicosis caused by Malva parviflora was required after 4 horses from the same farm developed severe muscle fasciculations, tachycardia, sweating and periods of recumbency leading to death or euthanasia after ingesting the plant. To describe historical, clinical, clinicopathological and pathological findings of 4 horses with suspected M. parviflora toxicosis. The role of cyclopropene fatty acids (found in M. parviflora) and mechanism for toxicosis are proposed. Case series. Historical, physical examination, clinicopathological and pathological findings are reported. Due to similarities with atypical myopathy or seasonal pasture myopathy acyl carnitine profiles were performed on sera from 2 cases and equine controls. Presence of cyclopropene fatty acids was also examined in sera of 2 cases. M. parviflora had been heavily grazed by the horses with little other feed available. Horse 1 deteriorated rapidly and was subjected to euthanasia. Horse 2 was referred to hospital where severe myocardial disease and generalised myopathy was determined; this horse was subjected to euthanasia 36 h after admission. Horse 3 died rapidly and Horse 4 was subjected to euthanasia at onset of clinical signs. Post-mortem examinations performed on 3 horses revealed acute, multifocal cardiac and skeletal myonecrosis. Myocyte glycogen accumulation was absent when examined in Horse 2. Acyl carnitine profiles revealed increased C14-C18 acyl carnitine concentrations in cases relative to controls. Cyclopropene fatty acids were detected in sera of cases but not controls. These findings suggest aetiology different to that of atypical myopathy or seasonal pasture myopathy. We hypothesise that cyclopropene fatty acids in M. parviflora interfere with fatty acid β-oxidation in horses in negative energy balance, causing the clinical signs and abnormal acyl carnitine profiles. These equine cases suggest a pathophysiological course that closely mimics the human genetic condition very