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Sample records for carnitine o-palmitoyltransferase

  1. Treatment of carnitine deficiency.

    Science.gov (United States)

    Winter, S C

    2003-01-01

    Carnitine deficiency is a secondary complication of many inborn errors of metabolism. Pharmacological treatment with carnitine not only corrects the deficiency, it facilitates removal of accumulating toxic acyl intermediates and the generation of mitochondrial free coenzyme A (CoA). The United States Food and Drug Administration (US FDA) approved the use of carnitine for the treatment of inborn errors of metabolism in 1992. This approval was based on retrospective chart analysis of 90 patients, with 18 in the untreated cohort and 72 in the treated cohort. Efficacy was evaluated on the basis of clinical and biochemical findings. Compelling data included increased excretion of disease-specific acylcarnitine derivatives in a dose-response relationship, decreased levels of metabolites in the blood, and improved clinical status with decreased hospitalization frequency, improved growth and significantly lower mortality rates as compared to historical controls. Complications of carnitine treatment were few, with gastrointestinal disturbances and odour being the most frequent. No laboratory or clinical safety issues were identified. Intravenous carnitine preparations were also approved for treatment of secondary carnitine deficiency. Since only 25% of enteral carnitine is absorbed and gastrointestinal tolerance of high doses is poor, parenteral carnitine treatment is an appealing alternative therapeutic approach. In 7 patients treated long term with high-dose weekly to daily venous boluses of parenteral carnitine through a subcutaneous venous port, benefits included decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake. Port infections were the most troubling complication. Theoretical concerns continue to be voiced that carnitine might result in fatal arrhythmias in patients with long-chain fat metabolism defects. No published clinical studies substantiate these

  2. Genomics of the human carnitine acyltransferase genes

    NARCIS (Netherlands)

    van der Leij, FR; Huijkman, NCA; Boomsma, C; Kuipers, JRG; Bartelds, B

    2000-01-01

    Five genes in the human genome are known to encode different active forms of related carnitine acyltransferases: CPT1A for liver-type carnitine palmitoyltransferase I, CPT1B for muscle-type carnitine palmitoyltransferase I, CPT2 for carnitine palmitoyltransferase II, CROT for carnitine octanoyltrans

  3. Novel aspects of carnitine function and metabolism

    OpenAIRE

    Violante, Sara Liliana Nunes, 1983-

    2013-01-01

    Tese de doutoramento, Farmácia (Bioquímica), Universidade de Lisboa, Faculdade de Farmácia, 2013 Normal functioning of fatty acid oxidation and energy metabolism depends on carnitine. Although this compound has been extensively studied over the years, some aspects of carnitine metabolism and function remain unclear. This thesis aimed to: 1) elucidate the reverse action of the carnitine shuttle in the mitochondrial detoxification of intermediates accumulating in mitochondrial fatty acid β-o...

  4. Tissue carnitine reserves of newborn infants.

    Science.gov (United States)

    Shenai, J P; Borum, P R

    1984-07-01

    This study assessed the tissue reserves of carnitine at birth in a group of neonates (n = 22) of varying gestational age dying within 24 h of birth, prior to possible changes in carnitine status induced by postnatal intervention. Tissue carnitine concentration was highest in the muscle in each infant. The mean (+/- SD) muscle carnitine concentration of 8.4 +/- 3.6 nmol/mg noncollagen protein (NCP) in very immature infants (less than or equal to 1000 g birth weight) was significantly lower than the corresponding mean (+/- SD) values of 14.0 +/- 3.2 nmol/mg NCP in larger preterm infants (1001-2500 g; P less than 0.01) and 19.4 +/- 2.6 nmol/mg NCP in term infants (greater than or equal to 2501 g; P less than 0.001). Muscle carnitine concentration correlated positively with gestational age (r = 0.832; P less than 0.001) and with body dimensions. Liver and heart carnitine concentrations did not correlate significantly with gestation or body dimensions. The mean (+/- SD) liver carnitine concentration for all the neonates as a group was 4.1 +/- 1.5 nmol/mg NCP. The mean (+/- SD) heart carnitine concentration was 4.7 +/- 1.3 nmol/mg NCP. In comparison to adult controls, tissue carnitine concentrations were markedly lower in neonates, particularly in immature newborns. These data suggest that newborn infants, especially premature babies, are born with limited tissue reserves of carnitine and are therefore at an increased risk for developing carnitine deficiency and its adverse effects in the postnatal period, particularly if maintained on carnitine-free intravenous nutrition for prolonged periods of time.

  5. 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 p

  6. 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...

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

    OpenAIRE

    Roberto Barbosa Bazotte; Gisele Lopes-Bertolini

    2012-01-01

    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 c...

  8. 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.

  9. Muscle contraction increases carnitine uptake via translocation of OCTN2

    International Nuclear Information System (INIS)

    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 (CLuptake) of L-[3H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CLuptake of [14C]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 CLuptake of L-[3H]carnitine in the contracting muscles increased 1.4–1.7-fold as compared to that in the contralateral resting muscles (p uptake of [14C]IAP was much higher than that of L-[3H]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.

  10. Systemic carnitine deficiency exacerbated by a strict vegetarian diet.

    OpenAIRE

    Etzioni, A.; Levy, J; Nitzan, M; Erde, P; Benderly, A

    1984-01-01

    A 12-year old boy suffered episodes of vomiting, lethargy, and hypoglycaemia from the age of 1 year. Adhering to a vegetarian diet caused an increase in frequency and severity of the attacks. It was found that he was suffering from systemic carnitine deficiency that responded promptly to treatment with L-carnitine.

  11. Muscle contraction increases carnitine uptake via translocation of OCTN2.

    Science.gov (United States)

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

    2012-02-24

    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 (pmuscle 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 (pmuscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  12. Patient with Eating Disorder, Carnitine Deficiency and Dilated Cardiomyopathy.

    Science.gov (United States)

    Fotino, A Domnica; Sherma, A

    2015-01-01

    Dilated cardiomyopathy is characterized by a dilated and poorly functioning left ventricle and can result from several different etiologies including ischemic, infectious, metabolic, toxins, autoimmune processes or nutritional deficiencies. Carnitine deficiency-induced cardiomyopathy (CDIM) is an uncommon cause of dilated cardiomyopathy that can go untreated if not considered. Here, we describe a 30-year-old woman with an eating disorder and recent percutaneous endoscopic gastrotomy (PEG) tube placement for weight loss admitted to the hospital for possible PEG tube infection. Carnitine level was found to be low. Transthoracic echocardiogram (TTE) revealed ejection fraction 15%. Her hospital course was complicated by sepsis from a peripherally inserted central catheter (PICC). She was discharged on a beta-blocker and carnitine supplementation. One month later her cardiac function had normalized. Carnitine deficiency-induced myopathy is an unusual cause of cardiomyopathy and should be considered in adults with decreased oral intake or malabsorption who present with cardiomyopathy. PMID:27159507

  13. 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

  14. Survey of carnitine content of human semen using a semiquantitative auxanographic method: decreased semen total carnitine concentration in patients with azoospermia or severe oligozoospermia.

    Science.gov (United States)

    Soffer, Y; Shalev, D P; Weissenberg, R; Orenstein, H; Nebel, L; Lewin, L M

    1981-01-01

    A microbiological method, using the carnitine-requiring yeast, Torulopsis bovina ATCC 26014, was developed to identify samples of human semen which contained low levels (less than 250 micron M) of total carnitine. Of 399 semen samples from a male infertility clinic which were tested, 30 (7.5%) were low in carnitine. Of these, 14 were azoospermic and 16 were severely oligozoospermic. Some azoospermic samples (19 = 58%) and severely oligozoospermic samples (51 = 79%) did not give evidence of low carnitine concentrations. These results indicate that decreased total carnitine concentration in semen occurs in certain classes of azoospermic and severely oligozoospermic patients.

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

    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-(/sup 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.

  17. 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.

  18. A novel splice site mutation in neonatal carnitine palmitoyl transferase II deficiency.

    NARCIS (Netherlands)

    Smeets, R.J.P.; Smeitink, J.A.M.; Semmekrot, B.A.; Scholte, H.R.; Wanders, R.J.; Heuvel, L.P.W.J. van den

    2003-01-01

    Mitochondrial beta-oxidation of long-chain fatty acids requires the concerted action of three tightly integrated membrane-bound enzymes (carnitine palmitoyltransferase I and II and carnitine/acylcarnitine translocase) that transport them into mitochondria. Neonatal onset of carnitine palmitoyltransf

  19. 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 l....../L in fC0 was appropriate to identify c.95A > G homozygotes. The prevalence of PCD in the Faroe Islands is the highest reported in the world (1:297).......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...

  20. Cerebrospinal fluid carnitine levels in patients with Alzheimer's disease.

    Science.gov (United States)

    Rubio, J C; de Bustos, F; Molina, J A; Jiménez-Jiménez, F J; Benito-León, J; Martín, M A; Campos, Y; Ortí-Pareja, M; Cabrera-Valdivia, F; Arenas, J

    1998-03-01

    We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no significant correlation between FC and AC levels in CSF. FC and AC levels in CSF did not differ significantly between AD patients and controls, but plasma FC levels were significantly lower in AD patients. CSF and plasma FC and AC levels did not correlate with age, age at onset of AD, duration of AD, and scores of the Minimental State Examination of Folstein. Although these results suggest that CSF carnitine levels are apparently unrelated with the risk for AD, the trend of the FC/AC ratio to be higher in AD patients might suggest the possibility of a lower carnitine acetyltransferase activity in AD, as previously reported in some brain areas. PMID:9562266

  1. L- and DL-carnitine induce tetanic fade in rat neuromuscular preparation

    OpenAIRE

    Lopes G.; Bazotte R.B.; Curi R.; Alves-Do-Prado W.

    2003-01-01

    Carnitine, a structurally choline-like metabolite, has been used to increase athletic performance, although its effects on neuromuscular transmission have not been investigated. It is present in skeletal muscle and its plasma levels are about 30 to 90 µM. Using rat phrenic nerve diaphragm preparations indirectly and directly stimulated with high rate pulses, D-carnitine (30 and 60 µM), L-carnitine (60 µM) and DL-carnitine (60 µM) were shown to induce tetanic fade (D-carnitine = 19.7 ± 3.1%, N...

  2. Results of treatment of infertility in men by complex acetyl-L-carnitine and L-carnitine

    OpenAIRE

    V. V. Mikhaylichenko; A. I. Novikov; V. N. Fesenko; S. V. Fesenko; E. D. Kazimzade; L. M. Rodygin

    2014-01-01

    100 patients with various forms of patozoospermii were randomly divided equally into 2 groups. First group of patients administered complex of acetyl-L-carnitine and L-carnitine (SpermAktin ®) and alpha-tocopherol acetate for 3 months, in the second group of patients was carried out single-agent alpha-tocopherol acetate duration of 3 months. Ejaculate volume, viscosity and pH of seminal plasma, the concentration, motility and morphology were evaluated after 1.5 and 3 months of starting treatm...

  3. 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 p

  4. 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.

  5. 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....... The purpose of this study was to investigate and describe the association and pathophysiology of exposure to antibiotics containing pivalic acid and severe neurological and cardiac complications in six identified subjects suffering from PCD....

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

    OpenAIRE

    Ozorio, R.

    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 oxidation. To avoid accumulation of lipids, supplementation of dietary carnitine may be used to stimulate fatty acid oxidation and to regulate lipolysis. Previous studies have demonstrated that responses to carnitine administrat...

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

    OpenAIRE

    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...

  8. l-Carnitine improves cognitive and renal functions in a rat model of chronic kidney disease.

    Science.gov (United States)

    Abu Ahmad, Nur; Armaly, Zaher; Berman, Sylvia; Jabour, Adel; Aga-Mizrachi, Shlomit; Mosenego-Ornan, Efrat; Avital, Avi

    2016-10-01

    Over the past decade, the prevalence of chronic kidney disease (CKD) has reached epidemic proportions. The search for novel pharmacological treatment for CKD has become an area of intensive clinical research. l-Carnitine, considered as the "gatekeeper" responsible for admitting long chain fatty acids into cell mitochondria. l-Carnitine synthesis and turnover are regulated mainly by the kidney and its levels inversely correlate with serum creatinine of normal subjects and CKD patients. Previous studies showed that l-carnitine administration to elderly people is improving and preserving cognitive function. As yet, there are no clinical intervention studies that investigated the effect of l-carnitine administration on cognitive impairment evidenced in CKD patients. Thus, we aimed to investigate the effects of l-carnitine treatment on renal function and on the cognitive performance in a rat model of progressive CKD. To assess the role of l-carnitine on CKD condition, we estimated the renal function and cognitive abilities in a CKD rat model. We found that all CKD animals exhibited renal function deterioration, as indicated by elevated serum creatinine, BUN, and ample histopathological abnormalities. l-Carnitine treatment of CKD rats significantly reduced serum creatinine and BUN, attenuated renal hypertrophy and decreased renal tissue damage. In addition, in the two way shuttle avoidance learning, CKD animals showed cognitive impairment which recovered by the administration of l-carnitine. We conclude that in a rat model of CKD, l-carnitine administration significantly improved cognitive and renal functions.

  9. Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

    Institute of Scientific and Technical Information of China (English)

    Salim S Al-Rejaie; Abdulaziz M Aleisa; Abdulaziz A Al-Yahya; Saleh A Bakheet; Abdulmalik Alsheikh; Amal G Fatani; Othman A Al-Shabanah; Mohamed M Sayed-Ahmed

    2009-01-01

    AIM: To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis.METHODS: A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group. Rats in group 1 (control group) received a single intraperitoneal (i.p.) injection of normal saline.Animals in group 2 (carnitine-supplemented group) were given L-carnitine (200 mg/kg per day) in drinking water for 8 wk. Animals in group 3 (carnitine-depleted group) were given D-carnitine (200 mg/kg per day) and mildronate (200 mg/kg per day) in drinking water for 8 wk. Rats in group 4 (DENA group) were injected with a single dose of DENA (200 mg/kg, i.p.) and 2 wk later received a single dose of carbon tetrachloride (2 mL/kg) by gavage as 1:1 dilution in corn oil. Animals in group 5 (DENA-carnitine depleted group) received the same treatment as group 3 and group 4. Rats in group 6 (DENA-carnitine supplemented group) received the same treatment as group 2 and group 4.RESULTS: Administration of DENA resulted in a significant increase in alanine transaminase (ALT),gamma-glutamyl t ransferase (G-GT) , alkal ine phosphatase (ALP), total bilirubin, thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite (NOx) and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GSHPx),catalase (CAT) and total carnitine content in liver tissues. In the carnitine-depleted rat model, DENA induced a dramatic increase in serum ALT, G-GT, ALP and total bilirubin, as well as a progressive reduction in total carnitine content in liver tissues. Interestingly,L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes, TBARS and NOx, and a decrease in total carnitine, GSH, GSHPx,and CAT induced by DENA, compared with the control values. Histopathological examination of liver tissues confirmed the biochemical data, where L-carnitine prevented DENA-induced hepatic

  10. Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model

    Directory of Open Access Journals (Sweden)

    Mohamed M. Sayed-Ahmed

    2010-01-01

    Full Text Available In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day combined with mildronate (MD, 200 mg/kg/day and PLC (250 mg/kg/day, respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day. IFO significantly increased serum creatinine, blood urea nitrogen (BUN, urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB, lactate dehydrogenase (LDH, intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS in cardiac tissues and significantly decreased adenosine triphosphate (ATP and total carnitine and reduced glutathione (GSH content in cardiac tissues. In carnitine

  11. Results of treatment of infertility in men by complex acetyl-L-carnitine and L-carnitine

    Directory of Open Access Journals (Sweden)

    V. V. Mikhaylichenko

    2014-12-01

    Full Text Available 100 patients with various forms of patozoospermii were randomly divided equally into 2 groups. First group of patients administered complex of acetyl-L-carnitine and L-carnitine (SpermAktin ® and alpha-tocopherol acetate for 3 months, in the second group of patients was carried out single-agent alpha-tocopherol acetate duration of 3 months. Ejaculate volume, viscosity and pH of seminal plasma, the concentration, motility and morphology were evaluated after 1.5 and 3 months of starting treatment. In the first group of infertile men showed a significant improvement in the quality and quantity of semen compared with the second patient group.

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

    Science.gov (United States)

    Ozorio, Rodrigo O A; Van Ginneken, Vincent J T; Bessa, Rui J B; Verstegen, Martin W A; Verreth, Johan A J; Huisman, Elbertus A

    2010-04-01

    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, sixteen fish were induced to a 3-h swim (speed of 1.5 body length (BL)/s), while the other sixteen fish were kept under resting condition. Fish fed 1000 mg L-carnitine accumulated 3.5 and 5 times more L-carnitine in plasma and muscle, respectively, than fish fed the 15 mg L-carnitine. Muscle L-carnitine content was significantly lower in exercised fish than in rested fish. High dietary lipid level (fish oil) led to an increase in muscle n-3 PUFA content and a decrease in SFA and MUFA content. In liver, the increase in dietary lipid level resulted in an increased levels of both n-6 and n-3 PUFA. L-carnitine supplementation significantly decreased n-3 PUFA content. Exercise decreased n-3 PUFA in both muscle and liver. Plasma lactate and lactate dehydrogenase, normally associated with increased glycolytic processes, were positively correlated with exercise and inversely correlated with dietary L-carnitine level. L-carnitine supplementation reduced significantly the RQ from 0.72 to 0.63, and an interaction between dietary L-carnitine and lipid was observed (P influence the regulation of FA oxidation selectivity.

  13. 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)....

  14. The Effect of L-Carnitine on Oxidative Stress Responses of Experimental Contrast-Induced Nephropathy in Rats

    OpenAIRE

    BOYACIOGLU, Murat; TURGUT, Hulya; AKGULLU, Cagdas; Eryilmaz, Ufuk; KUM, Cavit; ONBASILI, Osman Alper

    2013-01-01

    ABSTRACT This study was conducted to investigate the prophylactic effects of carnitine against contrast-induced nephropathy (CIN) and its relation to oxidant/antioxidant status in kidney, liver, heart, spleen and lung tissues in a CIN rat model. Twenty-eight adult male Wistar rats were divided into 4 groups, the control, contrast media (CM), carnitine and contrast media+carnitine (CM+carnitine) groups. Animals were placed in individual metabolism cages, and on the 2nd day, rats were deprived ...

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

    OpenAIRE

    Jewell, D; Hahn, K.

    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.

  16. Betaine and L-carnitine transport by Listeria monocytogenes Scott A in response to osmotic signals

    NARCIS (Netherlands)

    Verheul, Annette; Glaasker, Erwin; Poolman, Bert; Abee, Tjakko

    1997-01-01

    The naturally occurring compatible solutes betaine and L-carnitine allow the food-borne pathogen Listeria monocytogenes to adjust to environments of high osmotic strength. Previously, it was demonstrated that L. monocytogenes possesses an ATP-dependent L-carnitine transporter. The present study reve

  17. 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.

  18. 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…

  19. 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

  20. 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

  1. Fluorescent derivatization combined with aqueous solvent-based dispersive liquid-liquid microextraction for determination of butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma.

    Science.gov (United States)

    Chen, Yi-Ching; Tsai, Chia-Ju; Feng, Chia-Hsien

    2016-09-16

    A novel aqueous solvent-based dispersive liquid-liquid microextraction (AS-DLLME) method was combined with narrow-bore liquid chromatography and fluorescence detection for the determination of hydrophilic compounds. A remover (non-polar solvent) and extractant (aqueous solution) were introduced into the derivatization system (acetonitrile) to obtain a water-in-oil emulsion state that increased the mass transfer of analytes. As a proof of concept, three quaternary ammonium substances, including butyrobetaine, l-carnitine and acetyl-l-carnitine, were also used as analytes and determined in pharmaceuticals, personal care products, food and human plasma. The analytes were derivatized with 4-bromomethylbiphenyl for fluorescence detection and improved retention in the column. The linear response was 10-2000nM for l-carnitine and acetyl-l-carnitine with a good determination coefficient (r(2)>0.998) in the standard solution. The detection limit for l-carnitine and acetyl-l-carnitine was 4.5 fmol. The method was also successfully applied to a 1μL sample of human plasma. In the linearity calculations for determining butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma, the determination coefficients ranged from 0.996 to 0.999. Linear regression exhibited good reproducibility and a relative standard deviation better than 7.50% for the slope and 9.06% for the intercept. To characterize highly hydrophilic compounds in various samples, the proposed method provides good sensitivity for a small sample volume with a low consumption of toxic solvents.

  2. Fluorescent derivatization combined with aqueous solvent-based dispersive liquid-liquid microextraction for determination of butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma.

    Science.gov (United States)

    Chen, Yi-Ching; Tsai, Chia-Ju; Feng, Chia-Hsien

    2016-09-16

    A novel aqueous solvent-based dispersive liquid-liquid microextraction (AS-DLLME) method was combined with narrow-bore liquid chromatography and fluorescence detection for the determination of hydrophilic compounds. A remover (non-polar solvent) and extractant (aqueous solution) were introduced into the derivatization system (acetonitrile) to obtain a water-in-oil emulsion state that increased the mass transfer of analytes. As a proof of concept, three quaternary ammonium substances, including butyrobetaine, l-carnitine and acetyl-l-carnitine, were also used as analytes and determined in pharmaceuticals, personal care products, food and human plasma. The analytes were derivatized with 4-bromomethylbiphenyl for fluorescence detection and improved retention in the column. The linear response was 10-2000nM for l-carnitine and acetyl-l-carnitine with a good determination coefficient (r(2)>0.998) in the standard solution. The detection limit for l-carnitine and acetyl-l-carnitine was 4.5 fmol. The method was also successfully applied to a 1μL sample of human plasma. In the linearity calculations for determining butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma, the determination coefficients ranged from 0.996 to 0.999. Linear regression exhibited good reproducibility and a relative standard deviation better than 7.50% for the slope and 9.06% for the intercept. To characterize highly hydrophilic compounds in various samples, the proposed method provides good sensitivity for a small sample volume with a low consumption of toxic solvents. PMID:27562416

  3. 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.

  4. 左旋肉毒碱的代谢与营养效应%Metabolic and nutritional effects of L-carnitine

    Institute of Scientific and Technical Information of China (English)

    GinfrancoGurarnieri

    2001-01-01

    Carnitine is a water solule quaternary ammonium compound,which isa natural constituent of higher organisms,in particular of cells of animal origin.In humans,carnitine is synthesized in liver,brain and kidney starting from protein-bound lysine and methionine.Skeletal and heart muscle cannot synthesize carnitine.Therefore,these tissues are entirely dependent on carnitine uptake from the blood.In tissues and in physiological fluids carnitine is present in a free and an esterified form.The proportion of esterified carnitine may vary considerably with nutritional conditions,exercise and disease states.Tissue carnitine content depends on many factors: dietary carnitine,lysine,methionine and co-factor intake,carnitine synthesis (in uremia carnitine synthesis in the kidney is obviously reduced or absent),carnitine transport inside and outside tissues,and carnitine excretion.The transport of long-chain fatty acid esters to sites of beta-oxidation in the mitochondrial matrix requires L-carnitine.Besides,carnitine acts as a sink and allows a shift of the acyl pressure from the mitochondria to the cytoplasm.It has been suggested that carnitine is also important for the transport of the acyl groups (metabolic energy)from one cell to another cell and into the appropriate cellular compartment.Tissue carnitine content is much higher htan tissue CoA content and so acylcarnitines may also serve as storage for metabolic energy.By modulating the tissue content of acyl-CoA compounds which inhibit many enzyme activities (e.g.pyruvate dehydrogenase activity),carnitine may regulate many metabolic pathways.Carnitine system is located in the crossroads of intermediate metabolism and carnitine deficiency and supplementation may affect lipid,glucose and protein metabolism (and eventually nutrition) not only in primary,but also in secondary carnitine deficiency.Some positive effects of carnitine supplementation have been reported in experimental studies,in newborns,in patients treated with

  5. 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

  6. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage.

    Science.gov (United States)

    Dalakas, M C; Leon-Monzon, M E; Bernardini, I; Gahl, W A; Jay, C A

    1994-04-01

    The use of zidovudine (AZT) for the treatment of acquired immunodeficiency syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, which is histologically characterized by the presence of muscle fibers with "ragged-red"-like features, red-rimmed or empty cracks, granular degeneration, and rods (AZT fibers). Because dysfunctioning muscle mitochondria may lead to defects of beta-oxidation of fatty acids, we examined the degree of neutral fat accumulation and muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT-induced myopathic symptoms of varying severity. Six patients with no AZT fibers had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7 patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++) increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked ( ) increase in lipid droplets, and reduced muscle carnitine levels (6 patients). Serial sections showed lipid globules often within "cracks" or vacuoles of the abnormal muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long-chain fatty acids, (2) reduction of muscle carnitine levels probably due to decreased carnitine uptake by the muscle, and (3) depletion of energy stores within the muscle fibers. The findings may have potential therapeutic implications in the treatment of AZT-induced myopathic symptoms using oral carnitine supplementation.

  7. Cryoprotective effect of L-carnitine on motility, vitality and DNA oxidation of human spermatozoa.

    Science.gov (United States)

    Banihani, S; Agarwal, A; Sharma, R; Bayachou, M

    2014-08-01

    Successful cryopreservation for human spermatozoa markedly influences the reproductive outcomes of assisted reproductive technologies. But in spite of its usefulness, cryopreservation significantly decreases sperm quality. l-carnitine has been found to improve the quality of spermatozoa in selected cases with male infertility. Here, we examined the efficacy of l-carnitine in improving sperm motility and vitality and reducing sperm DNA oxidation during cryopreservation. Semen samples from infertile patients (n = 22) were collected and analysed. Cryopreservation medium supplemented with l-carnitine was mixed with the semen at a ratio of 1 : 1 (v/v). The final l-carnitine concentration in each cryovial was 0.5 mg ml(-1) per 5 × 10(6) cell ml(-1) . Controls were cryopreserved without addition of l-carnitine. After 24 h of cryopreservation, thawed sperm samples were analysed for motility, vitality and DNA oxidation. Sperm vitality was assessed by the eosin-nigrosin test, while sperm DNA oxidation was measured by flow cytometry. Addition of l-carnitine significantly improved sperm motility and vitality (P 0.05) in the levels of DNA oxidation between samples and controls. In conclusion, l-carnitine improves human sperm motility and vitality, but has no effect on sperm DNA oxidation after cryopreservation.

  8. Reconstruction of the carnitine biosynthesis pathway from Neurospora crassa in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Franken, Jaco; Burger, Anita; Swiegers, Jan H; Bauer, Florian F

    2015-08-01

    Industrial synthesis of L-carnitine is currently performed by whole-cell biotransformation of industrial waste products, mostly D-carnitine and cronobetaine, through specific bacterial species. No comparable system has been established using eukaryotic microorganisms, even though there is a significant and growing international demand for either the pure compound or carnitine-enriched consumables. In eukaryotes, including the fungus Neurospora crassa, L-carnitine is biosynthesized through a four-step metabolic conversion of trimethyllysine to L-carnitine. In contrast, the industrial yeast, Saccharomyces cerevisiae lacks the enzymes of the eukaryotic biosynthesis pathway and is unable to synthesize carnitine. This study describes the cloning of all four of the N. crassa carnitine biosynthesis genes and the reconstruction of the entire pathway in S. cerevisiae. The engineered yeast strains were able to catalyze the synthesis of L-carnitine, which was quantified using hydrophilic interaction liquid chromatography electrospray ionization mass spectrometry (HILIC-ESI-MS) analyses, from trimethyllysine. Furthermore, the yeast threonine aldolase Gly1p was shown to effectively catalyze the second step of the pathway, fulfilling the role of a serine hydroxymethyltransferase. The analyses also identified yeast enzymes that interact with the introduced pathway, including Can1p, which was identified as the yeast transporter for trimethyllysine, and the two yeast serine hydroxymethyltransferases, Shm1p and Shm2p. Together, this study opens the possibility of using an engineered, carnitine-producing yeast in various industrial applications while providing insight into possible future strategies aimed at tailoring the production capacity of such strains.

  9. 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.

  10. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mariano Malaguarnera; Corrado Risino; Maria Pia Gargante; Giovanni Oreste; Gloria Barone; Anna Veronica Tomasello; Mario Costanzo; Matteo Angelo Cannizzaro

    2006-01-01

    AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia.METHODS: Fifthy-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations,including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine,short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects.RESULTS: When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine (P<0.005), 0.04 μmol/L in long chain acylcarnitine (P<0.05), 8.7 μmol/L in total carnitine (P<0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2μmol/L in free carnitine (P<0.001), 4.60 μmol/L in short chain acylcarnitine (P<0.001), and 0.60 μmol/L in long-chain acylcarnitine (P<0.005) and 17.4 μmol/L in total carnitine (P<0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine (P<0.001), 5.2 μmol/L in short-chain acylcarnitine (P< 0.001), 1.0 μmol/L in long chain acylcarnitine (P <0.001), and 21.8μmol/L in total carnitine (P<0.001).CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.

  11. 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.

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

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    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. Influences of Short -term Aerobic Exercise and Supplementation of Carnitine With or Without Choline on Body Weight, Serum Leptin and Carnitine as Well as Lipid Status In Male Rats

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    Neamat E. Hishem*, Bushra H. El-Zawahry*, Seham M.S. El Nakeeb**

    2006-12-01

    Full Text Available Background: Carnitine is essential for fatty acids translocation, muscles function and exercise performance. Choline is a lipotropic agent that prevents deposition of fat in the liver. The studies concerning the effects of carnitine and choline supplementation with exercise on carnitine status and serum leptin are rare. The aim of the present study was to study the effect of carnitine and its combination with choline, with or without exercise on body and total fat pad (TFP weights, serum carnitine, leptin, -hydroxy butyric acid (-HBA, triacylglycerols (TAG and Free Fatty acids (FFA. Also, total lipids (TL and TAG content of TFP and urinary carnitine were investigated. Material and Methods: 48 male rats were equally divided to the following groups: control (C, carnitine (5 g/Kg diet supplemented, carnitine plus choline (5 and 11.5 g /Kg diet respectively supplemented. Half of each group was subjected to short term aerobic exercise on manual treadmill, in which the speed and duration were gradually increased via the course of the experiment, to be 10 m/min for 20 min/day, 5 days/week in the last 2 weeks. Body weights were recorded weekly. After 6 weeks, The 24 hours urine was collected then the fasted rats were sacrificed and blood and the total fat pad (TFP were collected for analysis. Results: Carnitine supplementation, tended to decrease body weight, TFP, TAG content and serum FFA, and significantly decreased the TL content, serum leptin, TAG (P<0.0005. Carnitine feeding resulted in a significant elevation of serum carnitine, -HBA and urinary carnitine (P<0.0005, compared to sedentary control rats. These values became more pronounced on choline addition to the diet except for serum and urinary carnitine that reversed (i.e. decreased by choline addition. Exercise intervention resulted in a significant decrease in body weight, TFP, TL content and serum leptin, TAG and FFA. These values were more pronounced in both supplements with exercise

  14. L-carnitine alleviates sciatic nerve crush injury in rats:functional and electron microscopy assessments

    Institute of Scientific and Technical Information of China (English)

    Ümmü Zeynep Avsar; Umit Avsar; Ali Aydin; Muhammed Yayla; Berna Ozturkkaragoz; Harun Un; Murat Saritemur; Tolga Mercantepe

    2014-01-01

    Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.

  15. Betaine and Carnitine Derivatives as Herbicidal Ionic Liquids.

    Science.gov (United States)

    Pernak, Juliusz; Niemczak, Michał; Chrzanowski, Łukasz; Ławniczak, Łukasz; Fochtman, Przemysław; Marcinkowska, Katarzyna; Praczyk, Tadeusz

    2016-08-16

    This study focused on the synthesis and subsequent characterization of herbicidal ionic liquids based on betaine and carnitine, two derivatives of amino acids, which were used as cations. Four commonly used herbicides (2,4-D, MCPA, MCPP and Dicamba) were used as anions in simple (single anion) and oligomeric (two anions) salts. The obtained salts were subjected to analyzes regarding physicochemical properties (density, viscosity, refractive index, thermal decomposition profiles and solubility) as well as evaluation of their herbicidal activity under greenhouse and field conditions, toxicity towards rats and biodegradability. The obtained results suggest that the synthesized herbicidal ionic liquids displayed low toxicity (classified as category 4 compounds) and showed similar or improved efficacy against weed compared to reference herbicides. The highest increase was observed during field trials for salts containing 2,4-D as the anion, which also exhibited the highest biodegradability (>75 %). PMID:27374836

  16. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

    OpenAIRE

    Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.

    2013-01-01

    Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a micr...

  17. Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model

    OpenAIRE

    Sayed-Ahmed, Mohamed M; Darweesh, Amal Q.; Fatani, Amal J

    2010-01-01

    In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with ...

  18. 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.

  19. L-carnitine-supplemented parenteral nutrition improves fat metabolism but fails to support compensatory growth in premature Korean infants.

    Science.gov (United States)

    Seong, So-Hui; Cho, Soo-Chul; Park, Yongsoon; Cha, Youn-Soo

    2010-04-01

    We have previously shown that pregnant Korean mothers often have especially poor carnitine status, which may be responsible for the suboptimal carnitine levels of newborn Korean infants. This study tested the hypothesis that carnitine obtained from premature infant formula alone is adequate in sustaining optimal lipid metabolism and growth in premature infants. Accordingly, we investigated the effects of parenteral carnitine supplementation on carnitine status, growth parameters, and lipid metabolism in premature infants by measuring serum lipid profiles, carnitine and beta-hydroxybutyrate concentrations, and body weight, size, and length. Twenty-five low-birth weight Korean infants were randomly assigned to control (LCNS, n = 12) or L-carnitine-supplemented (10 mg/[kg d], LCS, n = 13) groups. On day 9, the triacylglycerol concentration was lower in the LCS group; but the high-density lipoprotein cholesterol concentration and free, acyl, and total carnitine and beta-hydroxybutyrate were significantly increased compared with the LCNS group. The ratio of acyl carnitine to free carnitine was significantly lower on day 5 in the LCS compared with the LCNS group. Body weight, height, Apgar score (1 and 5 minute), head circumference, and chest circumference were recorded on day 0; and body weight was measured again on days 5 and 9. Infant formula intake was recorded every day. There was no significant difference in body weight or growth parameters between the groups from days 0 to 9.Therefore, we concluded that, in low-birth weight infants, the addition of 10 mg/(kg d) supplemental carnitine significantly improves lipid profiles and serum carnitine level but does not enhance growth. PMID:20534325

  20. Molecular Mechanism of Inhibition of the Mitochondrial Carnitine/Acylcarnitine Transporter by Omeprazole Revealed by Proteoliposome Assay, Mutagenesis and Bioinformatics

    OpenAIRE

    Annamaria Tonazzi; Ivano Eberini; Cesare Indiveri

    2013-01-01

    The effect of omeprazole on the mitochondrial carnitine/acylcarnitine transporter has been studied in proteoliposomes. Externally added omeprazole inhibited the carnitine/carnitine antiport catalysed by the transporter. The inhibition was partially reversed by DTE indicating that it was caused by the covalent reaction of omeprazole with Cys residue(s). Inhibition of the C-less mutant transporter indicated also the occurrence of an alternative non-covalent mechanism. The IC50 of the inhibition...

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

    OpenAIRE

    Thomas F. Rau; Qing Lu; Shruti Sharma; Xutong Sun; Gregory Leary; Beckman, Matthew L.; Yali Hou; Wainwright, Mark S; Michael Kavanaugh; 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 neurop...

  2. Oxygen glucose deprivation in rat hippocampal slice cultures results in alterations in carnitine homeostasis and mitochondrial dysfunction.

    Directory of Open Access Journals (Sweden)

    Thomas F Rau

    Full Text Available 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.

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

    Science.gov (United States)

    Soumya, R; Carl, H; Vani, R

    2016-09-01

    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 (l-carnitine at a concentration of 10 mM) (iii) LC 30 (l-carnitine at a concentration of 30 mM) and (iv) LC 60 (l-carnitine at a concentration of 60 mM). Every fifth day, the biomarkers (haemoglobin, hemolysis, antioxidant enzymes, lipid peroxidation and protein oxidation products) were analysed in erythrocytes. Hemoglobin and protein sulfhydryls were insignificant during storage indicative of the maintenance of hemoglobin and sulfhydryls in all groups. Superoxide dismutase and malondialdehyde levels increased initially and decreased towards the end of storage. The levels of catalase and glutathione peroxidase were lower in experimentals than controls during storage. l-carnitine assisted the enzymes by scavenging the reactive oxygen species produced. Hemolysis increased in all groups with storage, elucidating that l-carnitine could not completely protect lipids and proteins from oxidative stress. Hence, this study opens up new avenues of using l-carnitine as a component of storage solutions with combinations of antioxidants in order to maintain efficacy of erythrocytes.

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

    International Nuclear Information System (INIS)

    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-[3H]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-[3H]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

  6. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

    Science.gov (United States)

    Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

    2013-02-01

    Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential. PMID:23138103

  7. 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.

  8. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

    Science.gov (United States)

    Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.; Lewis, James D.; Warrier, Manya; Brown, J. Mark; Krauss, Ronald M.; Tang, W. H. Wilson; Bushman, Frederic D.; Lusis, Aldons J.; Hazen, Stanley L.

    2013-01-01

    Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk. PMID:23563705

  9. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.

    Science.gov (United States)

    Koeth, Robert A; Wang, Zeneng; Levison, Bruce S; Buffa, Jennifer A; Org, Elin; Sheehy, Brendan T; Britt, Earl B; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D; DiDonato, Joseph A; Chen, Jun; Li, Hongzhe; Wu, Gary D; Lewis, James D; Warrier, Manya; Brown, J Mark; Krauss, Ronald M; Tang, W H Wilson; Bushman, Frederic D; Lusis, Aldons J; Hazen, Stanley L

    2013-05-01

    Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk. PMID:23563705

  10. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Newborn screening test system for amino acids... 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...

  11. Determination of free and total carnitine with a random-access chemistry analyzer.

    Science.gov (United States)

    Wan, L; Hubbard, R W

    1998-04-01

    Carnitine deficiency presents as a major problem in fatty acid oxidation. The use of a plasma carnitine assay can rapidly help to describe this deficiency. The method we describe here requires two simple steps of sample preparation, followed by automated analysis with the Beckman Synchron CX4 random-access chemistry analyzer. The goal of this method development was to reduce the cost of analysis and to allow a greater number of laboratories to perform this assay on demand within 1 h for both free and total carnitine. The method has a linearity of 0-150 micromol/L and a detection limit of 5 micromol/L. The inter- and intraday CVs are <20%. The method agreed closely with both the widely used RIA and spectrophotometric methods.

  12. 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.

  13. PPAR-γ regulates carnitine homeostasis and mitochondrial function in a lamb model of increased pulmonary blood flow.

    Directory of Open Access Journals (Sweden)

    Shruti Sharma

    Full Text Available OBJECTIVE: Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt. Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. METHODS AND RESULTS: siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2 and carnitine acetyltransferase (CrAT protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. CONCLUSION: Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow.

  14. Kinetics of carnitine palmitoyltransferase I (CPT I) in Chinese sucker (Myxocyprinus asiaticus) change with its development.

    Science.gov (United States)

    Liu, Cai-Xia; Luo, Zhi; Hu, Wei; Tan, Xiao-Ying; Zheng, Jia-Lang; Chen, Qi-Liang; Zhu, Qing-Ling

    2014-02-01

    The present study was conducted to evaluate the ontogeny and kinetic of CPT I in several tissues of the Chinese sucker Myxocyprinus asiaticus. To this end, liver, muscle and intestine tissues were examined at five various developmental stages of Chinese sucker: newly-hatched larvae, 68-day-old, 4-month-old, 1- and 2-year-old Chinese sucker, respectively. The total carnitine (TC) content in the liver increased from birth to 1-year-old Chinese sucker and then declined in the 2-year-old Chinese sucker. From the 68-day-old to the 1-year-old Chinese sucker, both free and total concentrations in muscle increased. Both acyl carnitine (AC) and TC concentrations in intestine were very variable at different stages. The ratio of AC to free carnitine (FC) in liver progressively increased from hatching to 4 months, and declined at the age of 1 year, and then increased by 2 years. In muscle, the highest and lowest ratios of AC/FC were observed at 68-days-old and 4 month-old Chinese sucker. The highest proportion of AC/FC in intestine was also observed at 68-day-old Chinese sucker. All the Chinese sucker larvae at hatching had a high value of the Michaelis constant (K(m)) for carnitine. Maximal velocity (V(max)) in intestine increased with age. V(max) in liver and muscle increased with age except a decrease at 4 months in liver and at 2 years in muscle. The FC concentration in the examined tissues at all developmental stages were less than the respective K(m), indicating that Chinese suckers require supplemental carnitine in their food to ensure that CPT I activity is not constrained by carnitine availability. PMID:24264360

  15. First Japanese Case of Carnitine Palmitoyltransferase II Deficiency with the Homozygous Point Mutation S113L.

    Science.gov (United States)

    Shima, Atsushi; Yasuno, Tetsuhiko; Yamada, Kenji; Yamaguchi, Miyoko; Kohno, Ryuichi; Yamaguchi, Seiji; Kido, Hiroshi; Fukuda, Hidetoshi

    2016-01-01

    Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inherited disorder related to recurrent episodes of rhabdomyolysis. The adult myopathic form of CPT II deficiency is relatively benign and difficult to diagnose. The point mutation S113L in CPT2 is very common in Caucasian patients, whereas F383Y is the most common mutation among Japanese patients. We herein present a case of CPT II deficiency in a Japanese patient homozygous for the missense mutation S113L. The patient showed a decreased frequency of rhabdomyolysis recurrence after the administration of a diet containing medium-chain triglyceride oil and supplementation with carnitine and bezafibrate. PMID:27629963

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

    OpenAIRE

    Kraft Matthias; Kraft Kathleen; Gärtner Simone; Mayerle Julia; Simon Peter; Weber Eckhard; Schütte Kerstin; Stieler Jens; Koula-Jenik Heide; Holzhauer Peter; Gröber Uwe; Engel Georg; Müller Cornelia; Feng You-Shan; Aghdassi Ali

    2012-01-01

    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)...

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

    OpenAIRE

    Jung, Samooel; Bae, Young Sik; Yong, Hae In; Lee, Hyun Jung; Seo, Dong Won; Park, Hee Bok; Lee, Jun Heon; Jo, Cheorun

    2015-01-01

    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 f...

  18. Contributions of phosphorylation to regulation of OCTN2 uptake of carnitine are minimal in BeWo cells.

    Science.gov (United States)

    Rytting, Erik; Audus, Kenneth L

    2008-02-01

    Physiological functions of organic cation transporters (OCTs) in the placenta include transporting essential nutrients from the maternal to fetal circulations. OCTN2 transports carnitine with high affinity, and the transport of several drugs has also been shown to be mediated by this transporter. In this work, the role of phosphorylation and dephosphorylation mechanisms in regulating OCTN2 was investigated by observing the effects of various activators and inhibitors of kinases and phosphatases on the uptake of carnitine in BeWo cells, a human choriocarcinoma trophoblast cell line frequently used as an in vitro model of the rate-limiting barrier for maternal-fetal exchange. Preincubation with genistein resulted in significant increases in both alkaline phosphatase (ALP) activity and carnitine uptake. Levamisole, an ALP inhibitor, caused a more substantial decrease in carnitine uptake than expected from its corresponding decrease in ALP activity. It was determined that levamisole competitively inhibits carnitine uptake, with a K(i) value of 1.01+/-0.05mM, and this effect has a greater role in decreasing carnitine uptake than any indirect effects of ALP inhibition upon OCTN2 function. Progesterone also competitively inhibited carnitine uptake (K(i)=48.6+/-5.0muM), but had no effect on ALP activity in BeWo cells. PMID:17977516

  19. Effects of ethanol feeding on the activity and regulation of hepatic carnitine palmitoyltransferase I

    NARCIS (Netherlands)

    Guzman, M.; Geelen, M.J.H.

    1988-01-01

    The effects of ethanol administration on activity and regulation of carnitine palmitoyltransferase I (CPT-I) were studied in hepatocytes isolated from rats fed a liquid, high-fat diet containing 36% of total calories as ethanol or an isocaloric amount of sucrose. Cells were isolated at several time

  20. 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 rep...

  1. 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.

  2. Carnitine: function, metabolism and value in hepatic failure during chronic alcohol intoxication

    Directory of Open Access Journals (Sweden)

    Alina Kępka

    2011-10-01

    Full Text Available Alcoholism is one of the most frequent dependences among people, leading to damage of the liver and death of the person. Chronic alcohol consumption decreases fatty acid oxidation by interfering with carnitine metabolism and citric acid cycle activity. Block in activity of the citric acid cycle caused by alcohol and its metabolites is partially compensated by increased ketone body production, which results in ketosis. Chronic administration of alcohol induces liver injury, inflammation, cirrhosis, focal necrosis and steatosis.L-carnitine (L-3-hydroxy-4-N, N, N-trimethylaminebutyric acid is an essential factor in fatty acid metabolism, which plays a major role in transport of activated long-chain fatty acids to sites of β-oxidation in mitochondria. Carnitine also stabilizes cell membranes by removing long-chain acyl-CoA and excess of the acyl group from the body. L-carnitine can be a useful and safe drug in the liver pathology induced by chronic ethanol exposure.

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

    NARCIS (Netherlands)

    Ozorio, R.

    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 oxidation. To avoid accu

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

    International Nuclear Information System (INIS)

    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)

  5. Effects of L-Carnitine Added to Erythropoietin in Anemic Chronic Renal Failure Patients on Hemodialysis.

    Directory of Open Access Journals (Sweden)

    N Taheri

    2006-10-01

    Full Text Available Introduction: Chronic renal disease (C.R.D is a pathophysiological process due to progressive and irreversible decrease in number and function of nephrons in the kidney. Anemia is one of the most important complications in CRD patients. Anemia is caused mainly due to diminished production of erythropoietin (EPO, which is treated by weekly injection of the EPO. L-carnitine added to EPO can increase the efficacy of EPO. Methods: Present study, from March 2003 until September 2004 (18 months, evaluates the effects of L-carnitine added to EPO in 30 patients at Shaheed Rahnemon hemodialysis center of Yazd. Each patient was administered one oral table (250 mg of L-carnitine, twice a day along with EPO for 90 days. EPO was in the form of injection 2000 iu/sc after dialysis.(three times per week. One questionnaire was completed for each patient, which included demographic characteristics, type of disease, duration of the hemodialysis, Hb and Hct levels, transferrin saturation and ferritin levels. Hb ,Hct and transferrin saturations were measured on days 1, 45 and 90. Results were analyzed by paired t test and analysis of variance. Results: Results of this study showed that the mean Hb levels and Hct were significantly raised up to 1.1 mg/dl (P.value<0.001 and 2.7% (P.Value<0.001, respectively. In addition, significant decrease of 5.75% in transferrin (P.Value< 0.001 and 121ng/ml in ferritin levels (P.Value< 0.001 was observed. Efficacy of EPO plus L-carnitine was affected only by duration of hemodialysis and not by age, sex or causes of CRD. Conclusion: L-carnitine added to EPO increases the efficacy of EPO after 3 months.

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

    International Nuclear Information System (INIS)

    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)

  7. Expression of genes involved in hepatic carnitine synthesis and uptake in dairy cows in the transition period and at different stages of lactation

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    Schlegel Gloria

    2012-03-01

    Full Text Available Abstract Background In rodents and pigs, it has shown that carnitine synthesis and uptake of carnitine into cells are regulated by peroxisome proliferator-activated receptor α (PPARA, a transcription factor which is physiologically activated during fasting or energy deprivation. Dairy cows are typically in a negative energy balance during early lactation. We investigated the hypothesis that genes of carnitine synthesis and uptake in dairy cows are enhanced during early lactation. Results mRNA abundances of PPARA and some of its classical target genes and genes involved in carnitine biosynthesis [trimethyllysine dioxygenase (TMLHE, 4-N-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1, γ-butyrobetaine dioxygenase (BBOX1] and uptake of carnitine [novel organic cation transporter 2 (SLC22A5] as well as carnitine concentrations in liver biopsy samples of 20 dairy cows in late pregnancy (3 wk prepartum and early lactation (1 wk, 5 wk, 14 wk postpartum were determined. From 3 wk prepartum to 1 wk postpartum, mRNA abundances of PPARΑ and several PPARΑ target genes involved in fatty acid uptake, fatty acid oxidation and ketogenesis in the liver were strongly increased. Simultaneously, mRNA abundances of enzymes of carnitine synthesis (TMLHE: 10-fold; ALDH9A1: 6-fold; BBOX1: 1.8-fold and carnitine uptake (SLC22A5: 13-fold and the concentration of carnitine in the liver were increased from 3 wk prepartum to 1 wk postpartum (P P P Conclusions The results of this study show for the first time that the expression of hepatic genes of carnitine synthesis and cellular uptake of carnitine is enhanced in dairy cows during early lactation. These changes might provide an explanation for increased hepatic carnitine concentrations observed in 1 wk postpartum and might be regarded as a physiologic means to provide liver cells with sufficient carnitine required for transport of excessive amounts of NEFA during a negative energy balance.

  8. Effects of L-carnitine supplementation to suckling piglets on carcass and meat quality at market age.

    Science.gov (United States)

    Lösel, D; Rehfeldt, C

    2013-07-01

    In a previous study, carnitine supplementation to piglets during the suckling period resulted in an increased total muscle fibre number at weaning in piglets of low birth weight. The objective of the present study was to investigate whether this effect is maintained until market age and whether this would attenuate the negative consequences of low birth weight on carcass and meat quality. Using a split-plot design with litter as block, sex as whole plot and treatment as subplot, the effects of early-postnatal l-carnitine supplementation on female and castrated male piglets of low birth weight were investigated on a total of 56 German Landrace piglets from 14 litters. From days 7 to 27 of age piglets were orally supplemented once daily with 400 mg of l-carnitine dissolved in 1 ml of water or received an equal volume of water without carnitine. From weaning (day 28) until slaughter (day 166 of age) all pigs were fed standard diets. At weaning, carnitine-supplemented piglets had a twofold increased concentration of free carnitine (P < 0.001) and a lower concentration of non-esterified fatty acids (P < 0.05) in blood plasma indicating that carnitine became bioavailable and increased fatty acid utilization during the period of supplementation. Growth performance was not influenced by treatment in any growth period. Dual-energy X-ray absorptiometry revealed no differences in body composition between groups in weeks 12, 16 and 20 of age. LW at slaughter, carcass weight, measures of meat yield and fat accretion, as well as body composition by chemical analyses and dissection of primal cuts did not differ between treatments. No differences between control and carnitine-treated pigs in total fibre number (P = 0.85) and fibre cross-sectional area (P = 0.68) in m. semitendinosus (ST) measured at slaughter could be observed. The carnitine group tended to exhibit a smaller proportion of slow-twitch oxidative fibres (P = 0.08), a greater proportion of fast-twitch glycolytic

  9. Potential Effect of L-Carnitine on the Prevention of Myocardial Injury after Coronary Artery Bypass Graft Surgery

    Directory of Open Access Journals (Sweden)

    Farzaneh Dastan

    2015-10-01

    Full Text Available Background: L-carnitine has been demonstrated to confer cardiac protection against ischemia reperfusion injury in animals. This study evaluates the effects of L-carnitine administration on cardiac biomarkers after coronary artery bypass graft (CABG surgery.Methods: One hundred thirty-four patients undergoing elective CABG surgery, without a history of myocardial ischemia or previous L-carnitine treatment, were enrolled and randomly assigned to an L-carnitine group ([n = 67], 3000 mg/d, started 2 days preoperatively and continued for 2 days after surgery or a control group (n = 67. CK-MB (creatine kinase, muscle- brain subunits and troponin T (TnT levels were assessed in all the patients before surgery as baseline levels and at 8 and 24 hours postoperatively.Results: Our study included 134 patients (99 [73.8%] males at a mean ± SD age of 59.94 ± 8.61 years who were candidates for CABG and randomized them into control or L-carnitine groups. The baseline demographic characteristics, including age (60.01 ± 9.23 in the L-carnitine group vs. 59.88 ± 7.98 in the control group and sex (54 [80.6%] in the L-carnitine group vs. 45 [67.2%] in the control group did not show any significant differences (p value=0.93 and 0.08, respectively. Patients in the L-carnitine group had lower levels of CK-MB (mean ± SD, 25.06 ± 20.29 in the L-carnitine group vs. 24.26 ± 14.61 in the control group, but the difference was not significant (p value = 0.28. TnT levels also showed no significant differences between the two groups (399.50 ± 378.91 in the L-carnitine group vs. 391.48 ± 222.02 in the control group; p value = 0.34. Conclusion: In this population of intermediate- to high-risk patients undergoing CABG surgery, L-carnitine did not reduce CK-MB and TnT levels.

  10. Three Transporters Mediate Uptake of Glycine Betaine and Carnitine by Listeria monocytogenes in Response to Hyperosmotic Stress

    OpenAIRE

    Angelidis, Apostolos S.; Smith, Gary M.

    2003-01-01

    The uptake and accumulation of the potent osmolytes glycine betaine and carnitine enable the food-borne pathogen Listeria monocytogenes to proliferate in environments of elevated osmotic stress, often rendering salt-based food preservation inadequate. To date, three osmolyte transport systems are known to operate in L. monocytogenes: glycine betaine porter I (BetL), glycine betaine porter II (Gbu), and a carnitine transporter OpuC. We investigated the specificity of each transporter towards e...

  11. The carnitine biosynthetic pathway in Arabidopsis thaliana shares similar features with the pathway of mammals and fungi.

    Science.gov (United States)

    Rippa, Sonia; Zhao, Yingjuan; Merlier, Franck; Charrier, Aurélie; Perrin, Yolande

    2012-11-01

    Carnitine is an essential quaternary ammonium amino acid that occurs in the microbial, plant and animal kingdoms. The role and synthesis of this compound are very well documented in bacteria, fungi and mammals. On the contrary, although the presence of carnitine in plant tissue has been reported four decades ago and information about its biological implication are available, nothing is known about its synthesis in plants. We designed experiments to determine if the carnitine biosynthetic pathway in Arabidopsis thaliana is similar to the pathway in mammals and in the fungi Neurospora crassa and Candida albicans. We first checked for the presence of trimetyllysine (TML) and γ-butyrobetaine (γ-BB), two precursors of carnitine in fungi and in mammals, using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Both compounds were shown to be present in plant extracts at concentrations in the picomole range per mg of dry weight. We next synthesized deuterium-labeled TML and transferred A. thaliana seedlings on growth medium supplemented with 1 mM of the deuterated precursor. LC-ESI-MS/MS analysis of plant extracts clearly highlighted the synthesis of deuterium labeled γ-BB and labeled carnitine in deuterated-TML fed plants. The similarities between plant, fungal and mammalian pathways provide very useful information to search homologies between genomes. As a matter of fact the analysis of A. thaliana protein database provides homology for several enzymes responsible for carnitine synthesis in fungi and mammals. The study of mutants affected in the corresponding genes would be very useful to elucidate the plant carnitine biosynthetic pathway and to investigate further the role of carnitine in plant physiology.

  12. Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock.

    OpenAIRE

    Winter, B. K.; Fiskum, G; Gallo, L. L.

    1995-01-01

    Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and trea...

  13. 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.

  14. Cellular Metabolism and Dose Reveal Carnitine-Dependent and -Independent Mechanisms of Butyrate Oxidation in Colorectal Cancer Cells.

    Science.gov (United States)

    Han, Anna; Bennett, Natalie; MacDonald, Amber; Johnstone, Megan; Whelan, Jay; Donohoe, Dallas R

    2016-08-01

    Dietary fiber has been suggested to suppress colorectal cancer development, although the mechanisms contributing to this beneficial effect remain elusive. Butyrate, a fermentation product of fiber, has been shown to have anti-proliferative and pro-apoptotic effects on colorectal cancer cells. The metabolic fate of butyrate in the cell is important in determining whether, it acts as an HDAC inhibitor or is consumed as a short-chain fatty acid. Non-cancerous colonocytes utilize butyrate as the primary energy source whereas cancerous colonocytes increase glucose utilization through the Warburg effect. In this study, we show that butyrate oxidation is decreased in cancerous colonocytes compared to non-cancerous colonocytes. We demonstrate that colorectal cancer cells utilize both a carnitine-dependent and carnitine-independent mechanism that contributes to butyrate oxidation. The carnitine-dependent mechanism is contingent on butyrate concentration. Knockdown of CPT1A in colorectal cancer cells abolishes butyrate oxidation. In terms of selectivity, the carnitine-dependent mechanism only regulated butyrate oxidation, as acetate and propionate oxidation were carnitine-independent. Carnitine decreased the action of butyrate as an HDAC inhibitor and suppressed induction of H3 acetylation by butyrate in colorectal cancer cells. Thus, diminished oxidation of butyrate is associated with decreased HDAC inhibition and histone acetylation. In relation to the mechanism, we find that dichloroacetate, which decreases phosphorylation of pyruvate dehydrogenase, increased butyrate oxidation and that this effect was carnitine-dependent. In conclusion, these data suggest that colorectal cancer cells decrease butyrate oxidation through inhibition of pyruvate dehydrogenase, which is carnitine-dependent, and provide insight into why butyrate shows selective effects toward colorectal cancer cells. J. Cell. Physiol. 231: 1804-1813, 2016. © 2015 Wiley Periodicals, Inc. PMID:26661480

  15. Lotus leaf extract and L-carnitine influence different processes during the adipocyte life cycle

    Directory of Open Access Journals (Sweden)

    Stäb Franz

    2010-08-01

    Full Text Available Abstract Background The cellular and molecular mechanisms of adipose tissue biology have been studied extensively over the last two decades. Adipose tissue growth involves both an increase in fat cell size and the formation of mature adipocytes from precursor cells. To investigate how natural substances influence these two processes, we examined the effects of lotus leaf extract (Nelumbo nucifera-extract solution obtained from Silab, France and L-carnitine on human preadipocytes and adipocytes. Methods For our in vitro studies, we used a lotus leaf extract solution alone or in combination with L-carnitine. Utilizing cultured human preadipocytes, we investigated lotus leaf extract solution-induced inhibition of triglyceride incorporation during adipogenesis and possible effects on cell viability. Studies on human adipocytes were performed aiming to elucidate the efficacy of lotus leaf extract solution to stimulate lipolytic activity. To further characterize lotus leaf extract solution-mediated effects, we determined the expression of the transcription factor adipocyte determination and differentiation factor 1 (ADD1/SREBP-1c on the RNA- and protein level utilizing qRT-PCR and immunofluorescence analysis. Additionally, the effect of L-carnitine on beta-oxidation was analyzed using human preadipocytes and mature adipocytes. Finally, we investigated additive effects of a combination of lotus leaf extract solution and L-carnitine on triglyceride accumulation during preadipocyte/adipocyte differentiation. Results Our data showed that incubation of preadipocytes with lotus leaf extract solution significantly decreased triglyceride accumulation during adipogenesis without affecting cell viability. Compared to controls, adipocytes incubated with lotus leaf extract solution exhibited a significant increase in lipolysis-activity. Moreover, cell populations cultivated in the presence of lotus leaf extract solution showed a decrease in adipocyte

  16. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.

    Science.gov (United States)

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2015-03-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model. PMID:25465043

  17. Altered maternal thyroid function: Effect of L-carnitine supplementation on fetal and neonatal myocardial free fatty acid oxidation,in vitro

    OpenAIRE

    Kumar, Ratan

    1998-01-01

    Effect of L-carnitine supplementation on myocardial free fatty acid oxidation,in vitro, in offsprings born of hypothyroid and hyperthyroid mothers was studied in rats. L-carnitine supplementation stimulated myocardial fatty acid oxidation during gestational period in offspring born of control and hyperthyroid mothers. In contrast L-carnitine supplementation induced stimulation in myocardial fatty acid oxidation was very less in fetuses born of hypothyroid mothers. However, in neonates born of...

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

    Directory of Open Access Journals (Sweden)

    Mojtaba Kaviani

    2009-01-01

    Full Text Available (Received 31 October, 2009 ; Accepted 10 March, 2010AbstractBackground 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 widely used in various sporting fields to provide a boost to the recommended daily allowance. The aim of this study is to investigate the effects of acute L-carnitine administration on ventilatory breakpoint, an exercise performance during incremental exercise.Materials and methods: This study was double-blind, randomized and crossover in design. The subjects were 12 randomly selected active male physical education students, 21.75±0.64 years old, with a mean body mass index (BMI of 23.7±0.94kg/m2, divided into 2 groups. They received orally either 2g of L-carnitine dissolved in 200 ml of water, plus 6 drops of lemon juice or a placebo (6 ml lemon juice dissolved in 200 ml of water 90 minutes before they began to exercise on a treadmill. They performed a modified protocol of Conconi test to exhaustion. One-way analysis of variance with repeated measurements was used for data analysis.Results: The results showed that exercise performance improved in LC group (2980±155 meter compared with placebo group (2331±51 meter. Furthermore, no significant difference was found in ventilatory breakpoint between the two groups.Conclusion: This finding indicates that administration of L- Carnitine, 90 minutes prior to exercise may improve performance; despite the ventilatory breakpoint as one of the anaerobic system indices that had no effect. J Mazand Univ Med Sci 2009; 19(73: 43-50 (Persian.

  19. Regulation of carnitine palmitoyltransferase Ia under inflammmatory conditions in rat mesangial and primary liver cells

    OpenAIRE

    Eschenröder, Nina

    2008-01-01

    Energy substrate utilisation rates are regulated during development and in response to physiological and pathophysiological stimuli. Injury and inflammation result in marked changes in whole body lipid metabolism, including free fatty acid oxidation (Show et al., 1989). The regulation of fatty acid oxidation is most dependent on the enzyme carnitine palmitoyl transferase-I (CPT-I), which exists in two isoforms, hepatic CPT-Ialpha and muscle CPT-Iß isoform, and which catalyses the initial reac...

  20. Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema.

    Science.gov (United States)

    Conlon, Thomas M; Bartel, Jörg; Ballweg, Korbinian; Günter, Stefanie; Prehn, Cornelia; Krumsiek, Jan; Meiners, Silke; Theis, Fabian J; Adamski, Jerzy; Eickelberg, Oliver; Yildirim, Ali Önder

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD. PMID:26564208

  1. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non‐alcoholic malnourished rats

    OpenAIRE

    Rodrigues, Luciana P; Guilherme Vannucchi Portari; Gilberto João Padovan; Alceu Afonso Jordão; Vivian Suen; Julio Sergio Marchini

    2010-01-01

    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 nutrit...

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

    OpenAIRE

    DomingaLapi; LinaSabatino; GiovannaAltobelli

    2010-01-01

    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, perfus...

  3. Stabilization of the thermolabile variant S113L of carnitine palmitoyltransferase II

    OpenAIRE

    Motlagh, Leila; Golbik, Ralph; Sippl, Wolfgang; Zierz, Stephan

    2016-01-01

    Objective: Muscle carnitine palmitoyltransferase (CPT) II deficiency, the most common defect of lipid metabolism in muscle, is characterized by attacks of myoglobinuria without persistent muscle weakness. Methods: His6-N-hCPT2 (wild-type) and His6-N-hCPT2/S113L (variant) were produced recombinantly in prokaryotic host and characterized according to their functional and regulatory properties. Results: The wild-type and the variant S113L showed the same enzymatic activity and thermostability at...

  4. Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Judit Bene; Mária Figler; Katalin Komlósi; Viktória Havasi; Gábor Talián; Beáta Gasztonyi; Krisztina Horváth; Gyula Mózsik; Béla Hunyady; Béla Melegh

    2006-01-01

    AIM: To determine the plasma carnitine ester profile in adult patients with ulcerative culitis (UC) and compared with healthy control subjects.METHOD: Using ESI triple quadrupole tandem mass spectrometry, the carnitine ester profile was measured in 44 patients with UC and 44 age- and sex-matched healthy controls.RESULTS: There was no significant difference in the fasting free carnitine level between the patients with UC and the healthy controls. The fasting propionyl(0.331 ±0.019 vs0.392 ± 0.017 μmol/L), butyryl(0.219 ± 0.014 vs 0.265± 0.012), and isovalerylcarnitine (0.111 ± 0.008 vs 0.134± 0.008) levels were decreased in the UC patients. By contrast, the level of octanoyl- (0.147 ± 0.009 vs 0.114 ± 0.008),decanoyl- (0.180 ± 0.012 vs 0.137 ± 0.008), myristoyl(0.048 ± 0.003 vs 0.039 ± 0.003), palmitoyl- (0.128 ± 0.006vs 0.109 ± 0.004), palmitoleyl- (0.042±0.003vs 0.031 ± 0.002) and oleylcarnitine (0.183 ± 0.007vs 0.163 ± 0.007; P < 0.05 in all comparisons) were increased in the patients with UC.CONCLUSION: Our data suggest selective involvement of the carnitine esters in UC patients, probably due to their altered metabolism.

  5. Effect of L-carnitine supplementation on red blood cells deformability in hemodialysis patients.

    Science.gov (United States)

    Nikolaos, S; George, A; Telemachos, T; Maria, S; Yannis, M; Konstantinos, M

    2000-01-01

    Anemia is a serious problem in hemodialysis patients, the main cause of which is erythropoietin deficiency. After the discovery of recombinant human erythropoietin (rHuEpo) at the end of the last decade, the hematological profile of hemodialysis patients improved significantly but at considerable expense. The deformability of red blood cells (RBC) influences their microcirculation and tissue oxygen delivery along with their life span. We investigated the deformabilty of RBCs in 15 hemodialysis patients before and after three months on L-carnitine supplementation (30 mg/Kg body wt/dialysis session). We excluded from the study all patients who received blood transfusions three months before or during the study, patients who had hemorrhagic episodes, those with hyperparathyroidism or infections, and any who required surgical intervention during the study. The serum iron, folic acid and vitamin B-12 levels were kept normal during the duration of the study. The erythropoietin dose taken before the beginning of L-cartnitine supplementation was not changed. The deformability of RBCs before and after dialysis, prior to and following three months on L-carnitine was determined and compared to the deformability of RBCs from a control group. Hematocrit levels were measured before entry into the study and every month for three months. We found that the deformability of RBCs before the dialysis session was significantly greater than that found in the control group (t-test, p < 0.00001), and that there was a further increase after the end of the dialysis session. Three months following L-carnitine supplementation, we found a significant reduction of RBCs deformability (paired t-test, p < 0.004), and a significant increase in the hematocrit (ANOVA, p < 0.0001). We concluded that abnormalities in the deformability of RBCs improved after L-carnitine and that this was responsible for the increase in the hematocrit. This may allow a substantial reduction in rHuEpo dose. PMID:10718283

  6. Muscle-specific Deletion of Carnitine Acetyltransferase Compromises Glucose Tolerance and Metabolic Flexibility

    OpenAIRE

    Muoio, Deborah M.; Noland, Robert C.; Kovalik, Jean-Paul; Seiler, Sarah E.; Davies, Michael N.; DeBalsi, Karen L.; Ilkayeva, Olga R.; Stevens, Robert D.; Kheterpal, Indu; Zhang, Jingying; Jeffrey D Covington; Bajpeyi, Sudip; Ravussin, Eric; Kraus, William; Koves, Timothy R.

    2012-01-01

    The concept of “metabolic inflexibility” was first introduced to describe the failure of insulin resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate ...

  7. Short Term Administration of L-Carnitine can be Detrimental to the Ischemic Heart

    OpenAIRE

    Moslem Najafi; Alireza Garjani

    2013-01-01

    Previous studies have shown that L-carnitine (LC) supplementation may exert a cardioprotective effect in cardiomyopathy, prevent arrhythmias in myocardial infarction and increase exercise tolerance in angina. Interestingly, we demonstrated that short term preischemic administration of LC can be detrimental to ischemic heart. In isolated rat hearts treated with LC for 10 min before ischemia, a marked and concentration dependent arrhythmogenic activity were produced during both ischemia and rep...

  8. The pro-inflammatory cytokine tumor necrosis factor α stimulates expression of the carnitine transporter OCTN2 (novel organic cation transporter 2) and carnitine uptake via nuclear factor-κB in Madin-Darby bovine kidney cells.

    Science.gov (United States)

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

    2015-06-01

    Carnitine uptake into tissues is mediated mainly by the novel organic cation transporter 2 (OCTN2), whose expression is upregulated in the liver of early-lactating dairy cows. It has been shown recently that pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), stimulate OCTN2 expression and carnitine uptake in intestinal cells and inflamed intestinal mucosa. Given that many early-lactating dairy cows show typical signs of hepatic and systemic inflammation, such as elevated concentrations of circulating TNFα and activation of the key regulator of inflammation, nuclear factor κB (NF-κB), in tissues, it is possible that upregulation of OCTN2 and increase of carnitine uptake by TNFα is mediated by NF-κB, a mechanism that might contribute to the upregulation of OCNT2 in the liver of early-lactating dairy cows. Thus, in the present study, we tested the hypothesis that TNFα stimulates OCTN2 gene expression and carnitine uptake via NF-κB in the bovine Madin-Darby bovine kidney (MDBK) cell line. Treatment with TNFα caused activation of NF-κB, increased the mRNA and protein concentration of OCTN2, and stimulated the uptake of carnitine in MDBK cells. In contrast, combined treatment of MDBK cells with TNFα and the NF-κB inhibitor BAY 11-7085 completely blocked the effect of TNFα on OCTN2 mRNA and protein concentration and uptake of carnitine. These findings suggest that the bovine OCTN2 gene and carnitine uptake are regulated by NF-κB. Future studies are required to show the in vivo relevance of this regulatory mechanism in cattle.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Valproic Acid and topiramate induced hyperammonemic encephalopathy in a patient with normal serum carnitine.

    Science.gov (United States)

    Blackford, Martha G; Do, Stephanie T; Enlow, Thomas C; Reed, Michael D

    2013-04-01

    A 17-year-old female developed hyperammonemic encephalopathy 2 weeks after valproic acid (VPA), 500 mg twice a day, was added to her regimen of topiramate (TPM), 200 mg twice a day. She presented to the emergency department (ED) with altered mental status, hypotension, bradycardia, and lethargy. Laboratory analysis showed mild non-anion gap hyperchloremic acidosis, serum VPA concentration of 86 mg/L, and urine drug screen result that was positive for marijuana. She was admitted to the pediatric intensive care unit for persistent symptoms, prolonged QTc, and medical history. Blood ammonia concentrations were obtained because of her persistent altered mental status, initially 94 μmol/L and a peak of 252 μmol/L. A serum carnitine profile was obtained at the time of hyperammonemia and was found to be normal (results were available postdischarge). VPA and TPM were discontinued on day 1 and day 2, respectively, as the patient's blood ammonia concentration remained elevated. On day 3, her mental status had returned to baseline, and blood ammonia concentrations trended downward; by day 4 her blood ammonia concentration was 23 μmol/L. VPA has been associated with numerous side effects including hyperammonemia and encephalopathy. Recently, drug interactions with TPM and VPA have been reported; however, serum carnitine concentrations have not been available. We discuss the possible mechanisms that VPA and TPM may affect serum ammonia and carnitine concentrations and the use of levocarnitine for patients or treating toxicity.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet

    Institute of Scientific and Technical Information of China (English)

    Judit Bene; Katalin Komlósi; Beáta Gasztonyi; Márk Juhász; Zsolt Tulassay; Béla Melegh

    2005-01-01

    AIM: To determine the fasting plasma carnitine ester in patients with celiac disease.METHODS: We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet.RESULIS: The level of free camitine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced (4.703 ± 0.205 vs 10.227 ± 0.368 nmol/mL,P<0.01). The level of propionylcarnitine was 61.5%,butyrylcarnitine 56.9%, hexanoylcarnitine 75%,octanoylcarnitine 71.1%, octenoylcarnitine 52.1%,decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%,lauroylcarnitine 61.5%, miristoylcarnitine 66.7%,miristoleylcarnitine 62.5% and oleylcarnitine 81.1%in the celiac disease patients compared to the control values, respectively (P<0.01).CONCLUSION: The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.

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

    International Nuclear Information System (INIS)

    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)

  15. Comparison of the Effects of Varicocelectomy and Oral L-carnitine on Sperm Parameters in Infertile Men with Varicocele

    Science.gov (United States)

    Ghaderi, Ebrahim; Ganji, Omid

    2016-01-01

    Background Varicocele is defined as dilated and twisted veins of the pampiniform plexus in the spermatic cord. It is the most common cause of male infertility. There are various medical and surgical procedures for the treatment of this disease. Aim This study was aimed to compare the effects of oral administration of L-Carnitine and varicocelectomy on spermogram parameters. Materials and Methods This study was conducted as a double blind clinical trial without randomization. Inclusion criteria were, all married infertile men with varicocele. Patients chose their treatment personally and spermogram was carried out for all patients before and after the third and sixth months of treatment. Then, the sperm parameters of the two groups were compared using repeated measures ANOVA. Results In our study, trend of sperm count in the surgery group changed from 22 to 28.61 million (vs 34.6 to 45.37 in L-Carnitine group), motility changed from 21.74 to 35.38 percent (vs 33.9 to 47.48 in L-Carnitine group), normal sperm morphology changed from 46.25 to 60 percent (vs 56.61 to 69.7 in L-Carnitine group) and volume of semen changed from 3.5 to 4.17 cc (vs 2.95 to 4.33 in L-Carnitine group). These values were not statistically different between the two groups. Conclusion Based on the results of this study, we can say that medicinal treatment by administration of oral L-Carnitine is as effective as varicocelectomy in improving semen parameters and can be used as an alternative to surgery for varicocele grade II. PMID:27190879

  16. Role of Protective Effect of L-Carnitine against Acute Acetaminophen Induced Hepatic Toxicity in Adult Albino Rats

    Directory of Open Access Journals (Sweden)

    Zeinab M. Gebaly* and Gamal M. Aboul Hassan

    2012-10-01

    Full Text Available Background: Acetaminophen, a widely used analgesic and antipyretic is known to cause hepatic injury in humans and experimental animals when administered in high doses. It was reported that toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing to the beta-oxidation of fatty acid in the mitochondria. It is a known antioxidant with protective effects against lipid peroxidation. This study aimed to investigate the possible beneficial effect of L-carnitine as an antioxidant agent against acetaminophen induced hepatic toxicity in rats. Material and Methods: Four rat groups (N=7 in each group. Group I is the control, group II received 500 mg/kg/ body weight of L-carnitine for 7 days by oral route, group III received 640/kg/ bw of acetaminophen by oral route, group IV acute acetaminophen group pretreated with L-carnitine for 7 days by gastric tube gavage tube. The liver of all rats were removed for investigation using light and electro microscopic studies. Results: Acetaminophen caused massive centrilobular necrosis and massive degenerative changes. The electron-microscopic study showed few mitochondria, increased fat droplets and scanty smooth endoplasmic reticulum (SER, rough endoplasmic reticulum (RER.These changes were reduced by L-carnitine pretreatment. Conclusion: those results suggest that acetaminophen results damage in the liver as an acute effect and L-carnitine ameliorated the adverse effects of acetaminophen via its antioxidant role

  17. Mitigation of statins-induced cytotoxicity and mitochondrial dysfunction by L-carnitine in freshly-isolated rat hepatocytes.

    Science.gov (United States)

    Abdoli, N; Azarmi, Y; Eghbal, M A

    2015-01-01

    Statins are widely used as anti hyperlipidemic agents. Hepatotoxicity is one of their adverse effects appearing in some patients. No protective agents have yet been developed to treat statins-induced hepatotoxicity. Different investigations have suggested L-carnitine as a hepatoprotective agent against drugs-induced toxicity. This study was designed to evaluate the effect of L-carnitine on the cytotoxic effects of statins on the freshly-isolated rat hepatocytes. Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via portal vein. Cells were treated with the different concentrations of statins (simvastatin, lovastatin and atorvastatin), alone or in combination with L-carnitine. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers. Furthermore, the effects of statins on cellular reduced and oxidized glutathione reservoirs were evaluated. In accordance with previous studies, an elevation in ROS formation, cellular oxidized glutathione and lipid peroxidation were observed after statins administration. Moreover, a decrease in cellular reduced glutathione level and cellular mitochondrial membrane potential collapse occurred. L-carnitine co-administration decreased the intensity of aforementioned toxicity markers produced by statins treatment. This study suggests the protective role of L-carnitine against statins-induced cellular damage probably through its anti oxidative and reactive radical scavenging properties as well as its effects on sub cellular components such as mitochondria. The mechanism of L-carnitine protection may be related to its capacity to facilitate fatty acid entry into mitochondria; possibly adenosine tri-phosphate or the reducing equivalents are increased, and the toxic effects of statins toward mitochondria are encountered.

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

    Directory of Open Access Journals (Sweden)

    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. Does L-carnitine increase serum TNF -α and IGF-1 during liver regeneration in the rat?

    OpenAIRE

    PEHLİVAN, Mevlüt

    2009-01-01

    Aim: We sought to evaluate the effect of L-carnitine administration on the levels of IGF-1, TNF-a, and lipid peroxidation during hepatic regeneration for up to 72 h in an experimental partial hepatic resection rat model. Materials and methods: Sixty rats were divided into 3 groups: control and low-dose (100 mg/kg) and high-dose (200 mg/kg) L-carnitine. Each group was divided into 2 sub groups (24 and 72 h after partial hepatectomy). Partial (70%) hepatectomy was performed after 7 days of int...

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

    OpenAIRE

    Murat Caloglu; Vuslat Yurut Caloglu; Tulin Yalta; Omer Yalcin; Cem Uzal

    2012-01-01

    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...

  1. L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake

    OpenAIRE

    Yakup Yürekli; Perihan Ünak; Çiğdem Yenisey; Türkan Ertay; Fazilet Zumrut Biber Müftüler; Emin İlker Medine

    2011-01-01

    Objective: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. Material and Methods: Male Wistar rats were randomly divided into six groups of six animals each. 1) Control (saline; 5 ml/kg intraperitoneally); 2) L-carnitine (CAR; 300 mg/kg intraperitoneally); 3) Amifostine (AMI; 200 mg /kg intraperitoneally); 4) Cisplatin (CIS;7 mg/k...

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

    OpenAIRE

    Ozorio, R.; Ginneken, van, CJJM Kees; Thillart, van den, G.; M.W.A. Verstegen; 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 isonitrogenous diets containing a fat level of 100 or 190 g kg-1 diet and one of the two levels of carnitine (15 and 1000 mg kg-1). Fish grew from 61 to 162 g in 10 wk. Thereafter, 6 fish per group swam v...

  3. Carnitine tailored Sensors on Surface Molecular Imprinting based on Graphene layers

    OpenAIRE

    Truta, Liliana A.A.N.A.; Nádia S. Ferreira; M. Goreti F. Sales

    2013-01-01

    III Jornadas de Electroquímica e Inovação (Electroquímica e Nanomateriais), na Universidade de Trás-os-Montes e Alto Douro, Vila Real, 16 a 17 de Setembro de 2013 A new biosensor based on surface molecularly imprinted polymer (MIP) on graphene layers was successfully developed. It consists in a 3D polymeric network created on top of surface and around the target template, Carnitine (CRT), a potential biomarker of ovary cancer. The polymeric structure was obtained after radical polyme...

  4. Effect of exogenous proline, betaine, and carnitine on growth of Listeria monocytogenes in a minimal medium.

    Science.gov (United States)

    Beumer, R R; Te Giffel, M C; Cox, L J; Rombouts, F M; Abee, T

    1994-04-01

    Three Listeria monocytogenes strains isolated from food or food-processing environments were used to assess the response of this species to salinity in a chemically defined minimal medium. Growth in a minimal medium containing five essential amino acids and glucose as a carbon and energy source was comparable to growth in a rich medium (brain heart infusion broth). In the absence and presence of 3% NaCl the final cell numbers reached in minimal medium were 10(9) and 10(7) CFU/ml, respectively. Growth under the latter conditions could not be detected by spectrophotometry by measuring A660. Apparently, this technique was not suitable for these experiments since the detection level was > 10(7) CFU/ml. Exogenously added proline (10 mM), trimethylglycine (betaine) (1 mM), and beta-hydroxy-gamma-N-trimethyl aminobutyrate (carnitine) (1 mM) significantly stimulated growth under osmotic stress conditions in minimal medium at both 37 and 10 degrees C. Betaine and carnitine are present in foods derived from plants and animals, respectively. Therefore, these compounds can contribute significantly to growth of L. monocytogenes in various foods at high osmolarities. PMID:8017923

  5. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.

    Science.gov (United States)

    Muoio, Deborah M; Noland, Robert C; Kovalik, Jean-Paul; Seiler, Sarah E; Davies, Michael N; DeBalsi, Karen L; Ilkayeva, Olga R; Stevens, Robert D; Kheterpal, Indu; Zhang, Jingying; Covington, Jeffrey D; Bajpeyi, Sudip; Ravussin, Eric; Kraus, William; Koves, Timothy R; Mynatt, Randall L

    2012-05-01

    The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance. By converting acetyl-CoA to its membrane permeant acetylcarnitine ester, CrAT regulates mitochondrial and intracellular carbon trafficking. Studies in muscle-specific Crat knockout mice, primary human skeletal myocytes, and human subjects undergoing L-carnitine supplementation support a model wherein CrAT combats nutrient stress, promotes metabolic flexibility, and enhances insulin action by permitting mitochondrial efflux of excess acetyl moieties that otherwise inhibit key regulatory enzymes such as pyruvate dehydrogenase. These findings offer therapeutically relevant insights into the molecular basis of metabolic inflexibility. PMID:22560225

  6. Effects of L-carnitine administration on growth performance, carcass traits, blood serum parameters and abdominal fatty acid composition of ducks.

    Science.gov (United States)

    Arslan, C; Citil, M; Saatci, M

    2003-10-01

    Effects of L-carnitine administration via drinking water on growth performance, carcass traits, blood serum parameters and abdominal fatty acid composition of ducks was examined. One hundred day-old Turkish native duck chicks were divided into two groups, each with five replicates and given the same diets with 0 and 200 mg/l carnitine chlorhydrate via drinking water. The study lasted 8 weeks, with the first 4 weeks as a starter and the last 4 weeks as grower period. At the end of the study five ducks were randomly selected from each subgroup for slaughter. Growth performance parameters of ducks were not affected significantly by L-carnitine administration. Live weight, daily weight gain, cumulative feed consumption and average feed conversion efficiency were found to be 1490 and 1621 g, 26.0 and 28.1 g, 5386 and 5662 g, 3.75 and 3.54 kg/kg in the control and in the carnitine groups respectively. L-carnitine administration did not effect carcass traits and serum cholesterol, total lipid, triglyceride and glucose levels. Total saturated fatty acid content of abdominal fat significantly decreased, mono- and polyunsaturated fatty acid content were not affected by L-carnitine administration. In conclusion, L-carnitine administration by drinking water did not affect growth performance, carcass traits and blood parameters in ducks.

  7. [Effects of panthenol and carnitine on aldehyde metabolic enzymes in rats with tetrachloromethane-induced liver injury].

    Science.gov (United States)

    Satanovskaia, V I; Pron'ko, P S; Gaĭshmanova, A V; Miskevich, D A

    2009-01-01

    Tetrachloromethane (2 g/kg, intragastric) produced a decrease in the activity of NAD- and NADH- dependent aldehyde dehydrogenases with high Km for aldehydes in rat liver. Panthenol and L-carnitine administered separately normalized the activity of aldehyde dehydrogenases, while a combination of the drugs did not produce any significant effect. PMID:19441727

  8. Stability of carboplatin, paclitaxel, and docetaxel with acetyl-l-carnitine during simulated Y-site administration.

    Science.gov (United States)

    Zhang, Yang; Scarlett, Cameron; Hutson, Paul

    2012-01-01

    The compatibility of acetyl-l-carnitine with three chemotherapy agents was studied during simulated Y-site administration. Acetyl-l-carnitine 30 mg/mL in 5% dextrose for injection (D5W) was combined with carboplatin 4 mg/mL, paclitaxel 2 mg/mL, and docetaxel 0.74 mg/mL in glass vials. Physical compatibility over the 4-hour storage at room temperature was assessed by visual examinations with unaided eye under fluorescent light and by measuring the percent transmittance at 600 nm. Chemical compatibility was measured by the percent of initial concentration remaining using stability-indicating high-performance liquid chromatographic-ultraviolet and high-performance liquid chromatographic-mass spectrometry methods. No visible particulate matter, haze, or color change was observed, and the percent transmittance was >95% for all admixtures. After a 4-hour incubation, 93.2% of the paclitaxel and 96.5% of docetaxel remained in separate mixtures with acetyl-l-carnitine. Carboplatin 4 mg/mL, paclitaxel 1.2 mg/mL, and docetaxel 0.74 mg/mL are physically and chemically compatible with acetyl-l-carnitine 30 mg/mLin D5W during a simulated 4-hour Y-site administration. PMID:23050317

  9. Short-term carnitine supplementation does not augment LCPomega3 status of vegans and lacto-ovo-vegetarians

    NARCIS (Netherlands)

    Fokkema, M Rebecca; van Rieke, Helen M.; Bauermann, O J; Smit, E N; Muskiet, F A J

    2005-01-01

    OBJECTIVE: Long-chain polyunsaturated omega-3 fatty acids (LCPomega3) synthesis, notably that of docosahexaenoic acid (DHA), from the precursor alpha-linolenic acid (ALA) proceeds with difficulty. We investigated whether carnitine supplementation augments the LCPomega3 status of apparently healthy v

  10. Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification

    NARCIS (Netherlands)

    Bruce, Clinton R.; Brolin, Camilla; Turner, Nigel; Cleasby, Mark E.; van der Leij, Feike R.; Cooney, Gregory J.; Kraegen, Edward W.

    2007-01-01

    A key regulatory point in the control of fatty acid ( FA) oxidation is thought to be transport of FAs across the mitochondrial membrane by carnitine palmitoyltransferase I (CPT I). To investigate the role of CPT I in FA metabolism, we used in vivo electrotransfer (IVE) to locally overexpress CPT I i

  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. Modulation of tissue fatty acids by L-carnitine attenuates metabolic syndrome in diet-induced obese rats.

    Science.gov (United States)

    Panchal, Sunil K; Poudyal, Hemant; Ward, Leigh C; Waanders, Jennifer; Brown, Lindsay

    2015-08-01

    Obesity and dyslipidaemia are metabolic defects resulting from impaired lipid metabolism. These impairments are associated with the development of cardiovascular disease and non-alcoholic fatty liver disease. Correcting the defects in lipid metabolism may attenuate obesity and dyslipidaemia, and reduce cardiovascular risk and liver damage. L-Carnitine supplementation was used in this study to enhance fatty acid oxidation so as to ameliorate diet-induced disturbances in lipid metabolism. Male Wistar rats (8-9 weeks old) were fed with either corn starch or high-carbohydrate, high-fat diets for 16 weeks. Separate groups were supplemented with L-carnitine (1.2% in food) on either diet for the last 8 weeks of the protocol. High-carbohydrate, high-fat diet-fed rats showed central obesity, dyslipidaemia, hypertension, impaired glucose tolerance, hyperinsulinaemia, cardiovascular remodelling and non-alcoholic fatty liver disease. L-Carnitine supplementation attenuated these high-carbohydrate, high-fat diet-induced changes, together with modifications in lipid metabolism including the inhibition of stearoyl-CoA desaturase-1 activity, reduced storage of short-chain monounsaturated fatty acids in the tissues with decreased linoleic acid content and trans fatty acids stored in retroperitoneal fat. Thus, L-carnitine supplementation attenuated the signs of metabolic syndrome through inhibition of stearoyl-CoA desaturase-1 activity, preferential β-oxidation of some fatty acids and increased storage of saturated fatty acids and relatively inert oleic acid in the tissues.

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

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    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

  14. The effects of exogenous l-carnitine on lipid peroxidation and tissue damage in an experimental warm hepatic ischemia-reperfusion injury model*

    OpenAIRE

    Canbaz, Hakan; Akca, Tamer; Tataroglu, Canten; Caglikulekci, Mehmet; Dirlik, Musa; Ayaz, Lokman; Ustunsoy, Ali Bora; Tasdelen, Bahar; Aydin, Suha

    2007-01-01

    Background:l-Carnitine is the essential endogenous factor for the transport of long-chain fatty acids from the cytoplasm to within the mitochondrion where the β-oxidation process takes place. l-Carnitine is a superoxide scavenger and an antioxidant that possesses an anti-ischemic action and a stabilizing effect on cell membranes. It may be of help in liver ischemia reperfusion injury. Results regarding the effects of l-carnitine on liver ischemia and reperfusion injury are few and conflicting.

  15. Correlation of Serum Free Carnitine with Serum Ferritin and Vitamin C Levels in Type II Diabetic Men

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    Ahmad Pourabbas

    2013-07-01

    Full Text Available Background: Diabetes is a major health problem worldwide. Type II diabetic patients are reported to have higher ferritin and lower vitamin C concentrations. Considering the role of ascorbic acid in carnitine biosynthesis and the limited information on free carnitine correlations with ferritin and vitamin C levels in diabetic patients without microvascular complications, this case-control study was conducted to determine ferritin and vitamin C levels in hyperlipidemic-diabetic men comparing to healthy controls; the correlation of free carnitine with ferritin and vitamin C levels were also studied in these patients.Methods: Thirty-five hyperlipidemic-diabetic and seventy healthy men, were included in the study by the convenience sampling method. Body Mass Index, blood pressure, fasting blood glucose, lipid profile, ferritin and vitamin C levels were assessed in both case and control groups; moreover, serum free carnitine was measured in both groups. Dietary assessments were performed using 24 hour recall and food frequency questionnaires.Results: Blood pressure, fasting blood glucose, cholesterol, triglyceride, LDL, and HDL concentrations were significantly higher in the case group. Mean serum ferritin concentrations were higher in diabetics comparing to controls (93.22±0.27 vs. 44.66±4.23 µg/l; whereas, mean plasma vitamin C in these patients were lower than the healthy subjects (0.68±0.07 vs. 0.89±0.05. Positive correlations were observed between free carnitine and vitamin C levels.Conclusion: According to the results, it could be suggested that vitamin C supplementation in diabetic patients with hyperlipidemia might be useful. In addition, inclusion of serum ferritin assay in routine evaluation of diabetic patients could be beneficial.

  16. Combination therapy with losartan and L-carnitine protects against endothelial dysfunction of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sleem, Mostafa; Taye, Ashraf; El-Moselhy, Mohamed A; Mangoura, Safwat A

    2014-12-01

    Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications and angiotensin II appears to play a pivotal role in this setting. The present study aimed to investigate whether the combination therapy with losartan and the nutritional supplement, L-carnitine can provide an additional protection against diabetes-associated endothelial dysfunction and elucidate the possible mechanism(s) underlying this effect. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in rat. Effects of losartan (20 mg/kg, orally, 3 months) and L-carnitine (200 mg/kg, orally, 3 months) on tumor necrosis factor (TNF)-α, oxidative stress parameters, endothelial nitric oxide synthase expression (eNOS), and vascular function were evaluated. Our results showed a marked increase in aortic superoxide anion (O2(-)) production and serum malondialdehyde (MDA) level alongside attenuating antioxidant enzyme capacities in diabetic rats. This was associated with a significant increase in anigiotensin II type 1 receptor gene expression and TNF-α serum level of diabetic rats alongside reducing aortic eNOS gene expression and nitric oxide (NO) bioavailability. The single or combined administration of losartan and L-carnitine significantly inhibited these changes. Additionally, the vascular endothelium-dependent relaxation with acetylcholine (ACh) in aortic diabetic rat was significantly ameliorated by the single and combined administration of losartan or L-carnitine. Noteworthy, the combination therapy exhibited a more profound response over the monotherapy. Collectively, our results demonstrate that the combined therapy of losartan and L-carnitine affords additive beneficial effects against diabetes-associated endothelial dysfunction, possibly via normalizing the dysregulated eNOS and reducing the inflammation and oxidative stress in diabetic rats.

  17. Exploration of lipid metabolism in relation with plasma membrane properties of Duchenne muscular dystrophy cells: influence of L-carnitine.

    Directory of Open Access Journals (Sweden)

    Françoise Le Borgne

    Full Text Available Duchenne muscular dystrophy (DMD arises as a consequence of mutations in the dystrophin gene. Dystrophin is a membrane-spanning protein that connects the cytoskeleton and the basal lamina. The most distinctive features of DMD are a progressive muscular dystrophy, a myofiber degeneration with fibrosis and metabolic alterations such as fatty infiltration, however, little is known on lipid metabolism changes arising in Duchenne patient cells. Our goal was to identify metabolic changes occurring in Duchenne patient cells especially in terms of L-carnitine homeostasis, fatty acid metabolism both at the mitochondrial and peroxisomal level and the consequences on the membrane structure and function. In this paper, we compared the structural and functional characteristics of DMD patient and control cells. Using radiolabeled L-carnitine, we found, in patient muscle cells, a marked decrease in the uptake and the intracellular level of L-carnitine. Associated with this change, a decrease in the mitochondrial metabolism can be seen from the analysis of mRNA encoding for mitochondrial proteins. Probably, associated with these changes in fatty acid metabolism, alterations in the lipid composition of the cells were identified: with an increase in poly unsaturated fatty acids and a decrease in medium chain fatty acids, mono unsaturated fatty acids and in cholesterol contents. Functionally, the membrane of cells lacking dystrophin appeared to be less fluid, as determined at 37°C by fluorescence anisotropy. These changes may, at least in part, be responsible for changes in the phospholipids and cholesterol profile in cell membranes and ultimately may reduce the fluidity of the membrane. A supplementation with L-carnitine partly restored the fatty acid profile by increasing saturated fatty acid content and decreasing the amounts of MUFA, PUFA, VLCFA. L-carnitine supplementation also restored muscle membrane fluidity. This suggests that regulating lipid metabolism

  18. Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline-deprived myocardium: the effects of carnitine.

    Science.gov (United States)

    Strilakou, Athina; Perelas, Apostolos; Lazaris, Andreas; Papavdi, Asteria; Karkalousos, Petros; Giannopoulou, Ioanna; Kriebardis, Anastasios; Panayiotides, Ioannis; Liapi, Charis

    2016-02-01

    Choline has been identified as an essential nutrient with crucial role in many vital biological functions. Recent studies have demonstrated that heart dysfunction can develop in the setting of choline deprivation even in the absence of underlying heart disease. Matrix metalloproteinases (MMPs) are responsible for extracellular matrix degradation, and the dysregulation of MMP-2 and MMP-9 has been involved in the pathogenesis of various cardiovascular disorders. The aim of the study was to investigate the role of MMPs and their inhibitors (TIMPs), in the pathogenesis of choline deficiency-induced cardiomyopathy, and the way they are affected by carnitine supplementation. Male Wistar Albino adult rats were divided into four groups and received standard or choline-deficient diet with or without L-carnitine in drinking water (0.15% w/v) for 1 month. Heart tissue immunohistochemistry for MMP-2, MMP-9, TIMP-1, and TIMP-2 was performed. Choline deficiency was associated with suppressed immunohistochemical expression of MMP-2 and an increased expression of TIMP-2 compared to control, while it had no impact on TIMP-1. MMP-9 expression was decreased without, however, reaching statistical significance. Carnitine did not affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. The pattern of TIMP and MMP modulation observed in a choline deficiency setting appears to promote fibrosis. Carnitine, although shown to suppress fibrosis, does not seem to affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. Further studies will be required to identify the mechanism underlying the beneficial effects of carnitine.

  19. Comparative acute effects of l-carnitine and dl-carnitine on hepatic catabolism of l-alanine and l-glutamine in rats

    Institute of Scientific and Technical Information of China (English)

    Gisele LOPES; Vilma A F G GAZOLA; Sharize B GALENDE; Wilson ALVES-DO-PRADO; Rui CURI; Roberto B BAZOTTE

    2004-01-01

    AIM: To compare the acute effects of l-carnitine (LCT) and dl-camitine (DLC) on hepatic catabolism of l-alanine andl-glutamine in rats. METHODS: Livers from 24 h fasted and fed rats were perfused in situ. The substrates l-alanine (5 mmol/L) and l-glutamine (5 mmol/L) were employed. The gluconeogenic and ureogenic activity was measured as the difference between the rates of glucose and urea released during and before the infusion of l-glutamine or l-alanine. RESULTS: LCT (60 μmol/L) but not DLC (60 μmol/L and 120 μmol/L) increased the production of glucose and urea froml-glutamine. However, neither LCT (60 μmol/L and 120 μmol/L) nor DLC (60 μmol/L and 240 μmol/L) showed any significant effect on hepatic glucose and urea production froml-alanine.CONCLUSION: The results showed a different acute effect of LCT and DLC on the activation of hepatic gluconeogenesis and ureagenesis promoted byl-glutamine, reinforcing the idea that DLC could not replace LCT.

  20. Synergistic Effect of Probiotics, Butyrate and l-Carnitine in Treatment of IBD

    Directory of Open Access Journals (Sweden)

    Mahsa Moeinian

    2013-07-01

    Full Text Available Genetic, environmental factors, dysregulation of immune system, intestinal microbes and oxidative stress are the most important factors that play the role in the pathogenesis of inflammatory bowel disease (IBD. Current treatments do not always result in complete remission and usually accompanied with several adverse effects. Recent studies showed that nuclear factor-kappa B (NF-κB, tumor necrosis factor-α (TNF-α and oxidative stress play the pivotal role in the induction of inflammation. Butyrate, l-Carnitine, and probiotics have the potential to control inflammation by reduction of main inflammatory cytokines, including NF-κB and TNF-α. They also stimulate antioxidant enzymes and inhibit IκB kinase (IKK. Regarding the beneficial effects of these three compounds in inflammation via several mechanisms, we hypothesize that the mixture of these compounds would be synergistically effective in reduction of inflammation and alleviation of IBD. Further experimental investigations are needed, to evaluate the hypothesis.

  1. Short Term Administration of L-Carnitine Can Be Detrimental to the Ischemic Heart

    Directory of Open Access Journals (Sweden)

    Moslem Najafi

    2014-03-01

    Full Text Available Previous studies have shown that L-carnitine (LC supplementation may exert a cardioprotective effect in cardiomyopathy, prevent arrhythmias in myocardial infarction and increase exercise tolerance in angina. Interestingly, we demonstrated that short term preischemic administration of LC can be detrimental to ischemic heart. In isolated rat hearts treated with LC for 10 min before ischemia, a marked and concentration dependent arrhythmogenic activity were produced during both ischemia and reperfusion as increases in the number of ventricular ectopic beats, ventricular tachycardia and incidence of ventricular fibrillation. We hypothesized that preischemic using of LC for an inadequate time may pose arrhythmogenic activity, due to incomplete metabolism of fatty acids which in turn lead to production of toxic long chain fatty acid metabolites and also because of interruption in glucose oxidation.

  2. Effects of L-carnitine and Pentoxifylline on the Activity of Lactate Dehydrogenase C4 isozyme and Motility of Testicular Spermatozoa in Mice

    OpenAIRE

    Aliabadi, Elham; Karimi, Fatemeh; Rasti, Mozhgan; Akmali, Masoumeh; Esmaeilpour, Tahereh

    2013-01-01

    Background Extracted sperm from the testis have poor motility. Moreover, their motility changes during their journey through epidydimis. Meanwhile, they face high concentration of L-carnitin. In addition, lactate dehydrogenase C4 (LDH-C4) gene disorders has been shown to cause impaired sperm motility, leading to infertility in male mice. The aim of this study was to evaluate sperm motility and LDH-C4 enzyme activity upon L-carnitine (LC) and Pentoxifylline (PTX) administrations in mice. Metho...

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

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    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.

  4. L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake

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    Yakup Yürekli

    2011-04-01

    Full Text Available Objective: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. Material and Methods: Male Wistar rats were randomly divided into six groups of six animals each. 1 Control (saline; 5 ml/kg intraperitoneally; 2 L-carnitine (CAR; 300 mg/kg intraperitoneally; 3 Amifostine (AMI; 200 mg /kg intraperitoneally; 4 Cisplatin (CIS;7 mg/kg intraperitoneally; 5 Cisplatin plus L-carnitine (CIS + CAR; 6 Cisplatin plus amifostine (CIS + AMI. L-carnitine and amifostine were injected 30 minutes before cisplatin in Group 5 and 6. Tc 99m DMSA, 7.4 MBq/0.2 ml, was injected through the tail vein 72 hours after the drug administration. Rats were killed and kidneys removed by dissection 2 hours after the injection of the radiopharmaceutical. The percentage of the injected dose per gram of kidney tissue (%ID/g was calculated. Renal function was monitored by measuring BUN and plasma levels of creatinine. Lipid peroxidation and glutathione content were determined by measuring malondialdehyde (MDA and reduced glutathione (GSH in kidney tissue homogenates. Results: Tc 99m DMSA uptake per gram tissue of the kidney as %ID/g was 29.54±4.72, 29.86 ± 7.47 and 26.37 ± 4.54 in the control, CAR and AMI groups respectively. %ID/g was the lowest of all the groups, 11.60±3.59 (p<0.01, in the cisplatin group. Carnitine or amifostine administration 30 minutes before cisplatin injection resulted a significant increase in %ID/g, 21.28±7.73 and 18.97±3.24 respectively, compared to those of cisplatin-treated rats (p<0.002. A marked increase in plasma BUN and creatinine indicating nephrotoxicity and acute renal failure was observed in the cisplatin-treated group. MDA and GSH levels were concordant with cisplatin-induced oxidative stress in the kidney tissue. Conclusion: The results showed that L-carnitine significantly

  5. The Effects of Different Levels of Dietary Protein and L-Carnitine on Blood Sugar and Lipids of the New GIFT Strain of Juvenile Nile Tilapia (Oreochromis niloticus

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    Gang Chen

    2009-01-01

    Full Text Available The new GIFT (Genetically Improved Farmed Tilapia strain of Nile tilapia is a popular cultivated fish in Asia, but intensive aquaculture using nutritionally imbalanced feed has led to disorder of lipid metabolisms. An 8-week feeding experiment was conducted in order to assess the effects of different levels of L-carnitine (0, 200, 400, 600, and 800 mg/kg and dietary protein (22, 25, and 28% on blood sugar and blood lipid contents of the new juvenile GIFT strain of Nile tilapia. Results showed that dietary protein and L-carnitine had significant influences on glucose (GLU, high-density lipoprotein–cholesterol (HDL-C, total cholesterol (TC, triglyceride (TG, and low-density lipoprotein–cholesterol (LDL-C in the blood serum. The contents of GLU and HDL-C increased with the increases in dietary protein and L-carnitine levels, while the contents of TC, LDL-C, and TG decreased with the increases in dietary protein and L-carnitine levels. The interactive effect of both dietary protein and L-carnitine was most significant on GLU (p = 0.0001, followed by TG (p = 0.001, TC (p = 0.005, HDL-C (p = 0.056, and LDL-C (p = 0.109. These results suggested that high levels of dietary protein and L-carnitine supplementation reduce blood lipids and the burden of the fish liver.

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

    International Nuclear Information System (INIS)

    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).

  7. EFFECT OF FATTY-ACID CONCENTRATE (FAC AND CARNITINE ON PERFORMANCE, PHYSIOLOGICAL CONDITION AND MEAT QUALITY OF BROILER CHICKENS

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    Ryadchikov V. G.

    2016-09-01

    Full Text Available An experiment was conducted to examine the effect of fatty acid concentrate (FAC, as a new source of energy and carnitine on performance, physiological condition and meat quality of broiler chickens. In experiment there were four groups of 80 chickens of cross Hubbard each (males: females=40:40 in age period 0-41 days. 1 group (control received in during the periods 0-14, 15-28 and 29-41days, sunflower oil (SO respectively 5.34%, 5.50%, and 6.10%, group 2 received the same amounts of FAC instead SO, 3 group - mixture SO:FAC (50:50, 4 group -FAC + 0,25% carnitine. Final body weight: 1 group = 2574±29 g, 2 group FAC= 2553±27 g 3 group SO + FAC = 2531±34 g., 4 group FAC+0,25 carnitine = 2520±34 g. Feed conversion, digestibility of nutrients, blood hematology and biochemistry, the condition of organs, meat quality and cutting of carcass of chickens on FAC had no any differences from the same signs in chicks on SO. Carnitine had a positive effect on chicken growth only in the period 0-14 and less 15-28 days; in the period 29-41 days daily gain was below, than that in 1-3 groups. Canitine reduced the content of liver fat. Outcome: FAC is a satisfactory source of energy, comparable with vegetable oils. The price of FAC is 30% lower in comparison with sunflower oil and soybean oils, therefore its use in broiler poultry farming instead of vegetable oils will be of great economic importance

  8. Contributions of Phosphorylation to Regulation of OCTN2 Uptake of Carnitine are Minimal in BeWo Cells

    OpenAIRE

    Rytting, Erik; Audus, Kenneth L.

    2007-01-01

    Physiological functions of organic cation transporters (OCTs) in the placenta include transporting essential nutrients from the maternal to fetal circulations. OCTN2 transports carnitine with high affinity, and the transport of several drugs has also been shown to be mediated by this transporter. In this work, the role of phosphorylation and dephosphorylation mechanisms in regulating OCTN2 was investigated by observing the effects of various activators and inhibitors of kinases and phosphatas...

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

    OpenAIRE

    Wang, Xiaoyu

    2015-01-01

    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 a...

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

    OpenAIRE

    Wang XY; Wang JQ; Wang ZH; Wang QJ; Li H.

    2015-01-01

    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 adver...

  11. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain

    OpenAIRE

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2014-01-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar ...

  12. Effects of L-Carnitine and Cinnamon Extract Treatment on Lens Crystallins of Rats Fed High Fructose Diet

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    Mohamed H. Mahfouz

    2011-01-01

    Full Text Available Problem statement: Rats fed high dietary fructose are documented to form an acquired model of insulin resistance; the present study aims to investigate possible changes in lens crystallins of rats fed high fructose diet and the effects of administration of each exogenous L-Carnitine (CA and Cinnamon Extract (CE on protein glycation, oxidative stress and redox homeostasis in this rat model. Approach: A total number of 60 male Wister rats of body weight 120-160 g were divided into 4 groups of 15 rats each. Group 1 received control diet, while groups 2, 3 and 4: rats received high fructose diet (60g/100 g diet. After 2 weeks from fructose feeding, animals of group 3 were treated with L-carnitine (300 mg g-1 body weight/day i.p., while animals of group 4 were treated with cinnamon extract (0.5 mL/rat/day orally. At the end of experimental period (30 days, serum levels of glucose and insulin were determined. Lenses of each animal were dissected; molecular weights of crystalline, oxidative stress markers, early glycation of lens proteins and carbonyl group were assayed. Results: A significant decline in antioxidants and increase in lipid peroxidation products, protein oxidation and protein glycation were observed in lens samples obtained from fructose-fed rats. Administration of each CA and CE to fructose-fed rats significantly attenuated oxidative damage and protein glycation and returned levels of antioxidants to near those in control group. Chromatographic analysis of lens crystalline of rats fed high fructose diet showed diffused peaks, indicating crystalline aggregation. Conclusion: The results of the present study indicate that dietary fructose disturbs lens integrity and administration of L-carnitine or cinnamon extract may safeguard the lens by minimizing the protein aggregation, preventing glycation and oxidative stress in animals fed high fructose diet. L-carnitine has more potent effects than CE in this animal model.

  13. Role of Protective Effect of L-Carnitine against Acute Acetaminophen Induced Hepatic Toxicity in Adult Albino Rats

    OpenAIRE

    Zeinab M. Gebaly* and Gamal M. Aboul Hassan

    2012-01-01

    Background: Acetaminophen, a widely used analgesic and antipyretic is known to cause hepatic injury in humans and experimental animals when administered in high doses. It was reported that toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing to the beta-oxidation of fatty acid in the mitochondria. It is a known antioxidant with protective effects against lipid peroxidati...

  14. Muscle alkali-soluble protein, carnitine, water and electrolytes in patients with persistent post-operative infection.

    Science.gov (United States)

    Soop, M; Forsberg, E; Thörne, A; Cederblad, G; Bergström, J; Forsberg, A M; Hultman, E

    1989-10-01

    The muscle contents of water, electrolytes, creatine, alkali-soluble protein (ASP) and carnitine were determined using percutaneous muscle biopsy technique. Seven patients with prolonged catabolic states and subsequent respiratory failure were studied. Twelve age- and sex-matched healthy subjects were used for comparison. The muscle content of alkali-soluble protein in relation to the content of DNA was less than half of control values, indicating a loss of more than 50% of muscle protein content. The muscle carnitine content was 25.9 +/- 6.5 mumol/g alkali-soluble protein, suggesting a preserved muscle carnitine concentration. Total muscle water was increased by over 20%, mainly due to an increase in extracellular water. Muscle sodium and chloride contents were doubled. The content of magnesium was slightly reduced but muscle potassium was normal. The marked depletion of muscle protein may have contributed to the requirements for artificial ventilation and the difficulties in weaning off the ventilator. The increase in muscle water masks the loss of metabolically active muscle tissue yielding low values for energy expenditure when relating to body weight. The benefit of the use of the ASP/DNA ratio in nutritional assessment is emphasised.

  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.

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

    International Nuclear Information System (INIS)

    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)

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

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    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.

  18. Advance of research of detection methods forL-carnitine%左旋肉碱检测方法研究进展

    Institute of Scientific and Technical Information of China (English)

    马兴; 高云; 崔颖; 张海滨; 高健会

    2015-01-01

    左旋肉碱是一种类维生素的氨基酸衍生物,广泛存在于生物体内,在脂肪酸代谢中起重要作用。近年来,左旋肉碱越来越广泛地应用于保健食品、减肥药、婴幼儿奶粉和运动员补充剂中,因此,对其进行准确定量检测面临更高的技术要求。目前,研究人员对左旋肉碱进行了有关生物化学、药代动力学及毒理学等方面的广泛研究,与此同时开发了大量用于检测食品、营养补充剂和配方药物中左旋肉碱的方法。本文简要介绍了左旋肉碱的性质、生理功能和应用,分类总结了已开发的左旋肉碱检测方法,展望了左旋肉碱检测方法的未来发展方向。%ABSTRACT:L-carnitine is a vitamin-like amino acid derivative, which is widely existed in organisms. L-carnitine plays an important role in fatty acids metabolism. In recent years,L-carnitine has been increasingly used in health foods, diet pills, infant formula and supplement for athletes. Therefore the accurate quantitative detection methods forL-carnitine are needed. So far,L-carnitine has been investigated in biochemical, pharmacokinetic and toxico-kinetic studies and thus many detection methods has been developed for the determination ofL-carnitine in foods, dietary supplements and pharmaceutical formulations. This article briefly introduced the properties, physiological functions and applications ofL-carnitine, classified and summarized the developed detection methods forL-carnitine, and discussed the future development ofL-carnitine detection methods.

  19. New molecularly-imprinted polymer for carnitine and its application as ionophore in potentiometric selective membranes.

    Science.gov (United States)

    Moret, Joséphine; Moreira, Felismina T C; Almeida, Sofia A A; Sales, M Goreti F

    2014-10-01

    Carnitine (CRT) is a biological metabolite found in urine that contributes in assessingseveral disease conditions, including cancer. Novel quick screening procedures for CRT are therefore fundamental. This work proposes a novel potentiometric device where molecularly imprinted polymers (MIPs) were used as ionophores. The host-tailored sites were imprinted on a polymeric network assembled by radical polymerization of methacrylic acid (MAA) and trimethylpropane trimethacrylate (TRIM). Non-imprinted polymers (NIPs) were produced as control by removing the template from the reaction media. The selective membrane was prepared by dispersing MIP or NIP particles in plasticizer and poly(vinyl chloride), PVC, and casting this mixture over a solid contact support made of graphite. The composition of the selective membrane was investigated with regard to kind/amount of sensory material (MIP or NIP), and the need for a lipophilic additive. Overall, MIP sensors with additive exhibited the best performance, with near-Nernstian response down to ~1×10(-4)mol L(-1), at pH5, and a detection limit of ~8×10(-5)mol L(-1). Suitable selectivity was found for all membranes, assessed by the matched potential method against some of the most common species in urine (urea, sodium, creatinine, sulfate, fructose and hemoglobin). CRT selective membranes including MIP materials were applied successfully to the potentiometric determination of CRT in urine samples. PMID:25175239

  20. 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. PMID:23308261

  1. L-carnitine esters as "soft", broad-spectrum antimicrobial amphiphiles.

    Science.gov (United States)

    Calvani, M; Critelli, L; Gallo, G; Giorgi, F; Gramiccioli, G; Santaniello, M; Scafetta, N; Tinti, M O; De Angelis, F

    1998-06-18

    A new class of antimicrobial, "soft", quaternary ammonium l-carnitine esters, of the type (CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-, has been designed, with R1 and R2 being in general long-chain alkyl substituents. The series shows good activity against a wide range of bacteria, yeasts, and fungi. Lipophilicity has been measured by RP-HPLC method to give the logarithm of the experimental capacity factor (log k'), and a quantitative relationship has been determined between log k' and the theoretical partition coefficient (CLOGP); also, bond-dipole descriptors have been introduced into calculations by accounting for polar moieties present within the apolar cores of the molecules, giving a more refined calculated capacity factor (log k'calcd). Finally the latter has been related to the antimicrobial activity (MIC values). The proposed models are predictive for the best broad-spectrum antimicrobial compound within the series. PMID:9632355

  2. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes

    Science.gov (United States)

    Calderon-Dominguez, María; Sebastián, David; Fucho, Raquel; Weber, Minéia; Mir, Joan F.; García-Casarrubios, Ester; Obregón, María Jesús; Zorzano, Antonio; Valverde, Ángela M.; Serra, Dolors

    2016-01-01

    The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders. PMID:27438137

  3. Decreased cerebrospinal fluid levels of L-carnitine in non-apolipoprotein E4 carriers at early stages of Alzheimer's disease.

    Science.gov (United States)

    Lodeiro, María; Ibáñez, Clara; Cifuentes, Alejandro; Simó, Carolina; Cedazo-Mínguez, Ángel

    2014-01-01

    Increasing evidence suggest that Alzheimer's disease (AD) is a heterogeneous disorder that includes several subtypes with different etiology and progression. Cerebrospinal fluid (CSF) is being used to find new biomarkers reflecting the complexity of the pathological pathways within this disease. We used CSF and clinical data from patients to investigate the status of asymmetric dimethyl-L-arginine, creatine, suberylglycine, and L-carnitine along AD progression. These molecules play important roles in mitochondrial function and dysfunction in mitochondrial metabolism are involved in AD pathology. We found that non-APOE4 carriers show lower levels of L-carnitine in CSF early in AD. L-carnitine levels correlate with amyloid-β (Aβ) levels and Mini-Mental State Examination score, but do not add to the specificity or sensitivity of the classical AD CSF biomarkers, Aβ42, phospho-tau, and total-tau. Our results suggest APOE genotype-dependent differences in L-carnitine synthesis or metabolism along AD, and insinuate that L-carnitine treatments would be more beneficial for AD patients not carrying the APOE4 isoform.

  4. 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.

  5. 左旋肉碱的生理功能及应用进展%The Physiological Function and Application of L-carnitine

    Institute of Scientific and Technical Information of China (English)

    ZHOU You-ya; WANG Xue

    2001-01-01

    L-carnitine is an essential matter of the body as protein, fat and water do. It is also a natual matter exsists in animal body and human body. With the advance of research,L-carnitine has been accepted and used widely. On the basis of consulting lots of reference,the paper summarizes the physiological function and application of L-carnitine.%L-肉碱如同蛋白质、脂肪、水一样,是人体必需的营养物质.随着研究的深入,L-肉碱已被人们广泛接受,并得到普遍应用.在查阅大量文献基础上,综述了L-肉碱的生理功能及应用情况.

  6. 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

    Flux control analysis of eight reactions involved in oxidative phosphorylation of mitochondria from rat quadriceps muscle was performed under circumstances resembling in vivo conditions of carbohydrate or fatty acid oxidation. The major flux control at a respiration rate of 55% of state 3...... with the fatty acid oxidation or transport. Flux control of ADP generation was specifically tested at three different respiration rates, 30, 55 and 75% of state 3. At all respiration rates control was higher with pyruvate and pyruvate + palmitoyl-carnitine compared with palmitoyl-carnitine as substrate. Also...... the control was lower at 75% compared to 30% of the state 3 respiration both with pyruvate and pyruvate + palmitoyl-carnitine as substrate, suggesting that muscle respiration moves from "demand control" to "supply control" as respiration increases....

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

    Directory of Open Access Journals (Sweden)

    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

  8. Effects of dietary supplementation with L-carnitine and fat on blood acid-base responses to handling in slaughter weight pigs.

    Science.gov (United States)

    Bertol, T M; Ellis, M; Hamilton, D N; Johnson, E W; Ritter, M J

    2005-01-01

    Blood acid-base responses to handling were evaluated in slaughter weight pigs fed diets supplemented with l-carnitine and fat. The study was carried out as a randomized block design with a 2 x 2 factorial arrangement of treatments: 1) dietary L-carnitine supplementation (0 vs. 150 ppm, as-fed basis); and 2) dietary fat supplementation (0 vs. 5%, as-fed basis). Sixty pigs (91.1 +/- 5.14 kg BW) were housed in mixed-gender groups of five and had ad libitum access to test diets (0.68% true ileal digestible lysine, 3,340 kcal of ME/kg, as-fed basis) for 3 wk. At the end of the feeding period (110.3 +/- 7.52 kg BW), pigs were subjected to a standard handling procedure, which consisted of moving individual animals through a facility (12.2 m long x 0.91 m wide) for eight laps (up and down the facility), using electric prods (two times per lap). There was no interaction between dietary L-carnitine and fat supplementation for any measurement. Pigs fed 150 ppm of supplemental L-carnitine had lower baseline blood glucose (P pressure of oxygen, and glucose, and also increased (P < 0.01) rectal temperature. Free fatty acid concentrations were increased by handling in pigs fed both 0 and 5% fat and 150 ppm L-carnitine. In conclusion, dietary L-carnitine supplementation at the level and for the feeding period evaluated in the current study had a relatively small but positive effect on decreasing blood pH changes in finishing pigs submitted to handling stress; however, dietary fat supplementation had little effect on blood acid-base balance. PMID:15583045

  9. Effect of L-carnitine supplementation on growth performance, nutrient utilization, and nitrogen balance of broilers fed with animal fat

    Directory of Open Access Journals (Sweden)

    P. Murali

    2015-04-01

    Full Text Available Aim: This experiment was conducted to evaluate the effect of L-carnitine supplementation on growth performance, nutrient utilization and nitrogen balance in broilers fed with animal fat. Materials and Methods: 80 day-old Cobb commercial broiler chicks were randomly assigned into two dietary treatment groups with four replicates of ten chicks each. The diets were isonitrogenous and isocaloric. The birds in both the control (T1 and treatment group (T2 were fed with a diet having 5% animal fat, while the treatment group (T2 was supplemented with 900 mg of L-carnitine. The birds were fed with standard broiler starter ration up to 4 weeks of age and finisher ration up to 6 weeks of age. Results: The average body weight (g, cumulative feed intake (g and cumulative feed conversion ratio belonging to groups T1 and T2 at 6th week of age were 2091.25 and 2151.11, 3976.49 and 4171.68, 1.97 and 1.96 respectively. The percentage availability of the nutrients of two experimental rations T1 and T2 was 68.23 and 68.00 for dry matter, 58.72 and 55.98 for crude protein, 73.85 and 71.35 for ether extract, 34.19 and 33.86 for crude fiber, 79.18 and 79.59 for nitrogen free extract, 70.24 and 70.03 for energy efficiency and nitrogen balance (g/day were 2.35 and 2.39, respectively. Conclusion: This study suggests that the supplementation of 900 mg L-carnitine in diet with added animal fat had no effect on growth performance, nutrient utilization, and nitrogen balance of broilers.

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

    OpenAIRE

    Kazemi-Fard M; Yousefi S; Dirandeh E; Rezaei M

    2015-01-01

    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 e...

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

    OpenAIRE

    Panchamoorthy Rajasekar; Carani Venkatraman Anuradha

    2007-01-01

    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 sho...

  12. Effect of Feed Additive on Base of L-carnitine in Drinking Water on Internal and External Egg Quality

    OpenAIRE

    Cyril Hrnčár; Martin Gašparovič; Ján Weis; Henrieta Arpášová; Veronika Pistová; Martin Fik; Jozef Bujko

    2016-01-01

    The objective of present study was to investigate the effect of feed additive on base of L-carnitine (30%) on some parameters of egg quality. Totally 40 White Leghorn laying hens were divided in two groups: control group (n=20) received drinking water without any additives and experimental group (n=20) received feed additive in dose 1 ml per 1.2 l of drinking water for a period of 5 days in 2 week intervals from 26 to 56 week of age. Hens in both groups were feeding ad libitum with commercial...

  13. Acetyl-L-carnitine improves behavior and dendritic morphology in a mouse model of Rett syndrome.

    Directory of Open Access Journals (Sweden)

    Laura R Schaevitz

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder affecting 1 in 10,000 girls. Approximately 90% of cases are caused by spontaneous mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2. Girls with RTT suffer from severe motor, respiratory, cognitive and social abnormalities attributed to early deficits in synaptic connectivity which manifest in the adult as a myriad of physiological and anatomical abnormalities including, but not limited to, dimished dendritic complexity. Supplementation with acetyl-L-carnitine (ALC, an acetyl group donor, ameliorates motor and cognitive deficits in other disease models through a variety of mechanisms including altering patterns of histone acetylation resulting in changes in gene expression, and stimulating biosynthetic pathways such as acetylcholine. We hypothesized ALC treatment during critical periods in cortical development would promote normal synaptic maturation, and continuing treatment would improve behavioral deficits in the Mecp2(1lox mouse model of RTT. In this study, wildtype and Mecp2(1lox mutant mice received daily injections of ALC from birth until death (postnatal day 47. General health, motor, respiratory, and cognitive functions were assessed at several time points during symptom progression. ALC improved weight gain, grip strength, activity levels, prevented metabolic abnormalities and modestly improved cognitive function in Mecp2 null mice early in the course of treatment, but did not significantly improve motor or cognitive functions assessed later in life. ALC treatment from birth was associated with an almost complete rescue of hippocampal dendritic morphology abnormalities with no discernable side effects in the mutant mice. Therefore, ALC appears to be a promising therapeutic approach to treating early RTT symptoms and may be useful in combination with other therapies.

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

    International Nuclear Information System (INIS)

    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 [3H]-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 Ca2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca2+-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 Ca2+ to the medium. This result was consistent with a competition between Ca2+ 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 Ca2+

  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. 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

  17. L-carnitine effectively improves the metabolism and quality of platelet concentrates during storage.

    Science.gov (United States)

    Deyhim, Mohammad Reza; Mesbah-Namin, Seyed Alireza; Yari, Fatemeh; Taghikhani, Mohammad; Amirizadeh, Naser

    2015-04-01

    Human platelets undergo structural and biochemical alternations during storage which are collectively called platelet storage lesion (PSL). PSL is characterized as metabolic and functionally changes. It causes decrease in platelet recovery and survival. Here, we evaluated the effect of L-carnitine (LC) on the metabolism, function, and mitochondrial metabolic activity of platelet during storage. Platelet-rich plasma was used to prepare platelet concentrate (PC) in Iranian Blood Transfusion Organization. For this purpose, ten PC bags from healthy donors were stored at 22 °C with gentle agitation in the presence or absence of LC. The effects of LC (15 mM) on the platelet quality were assessed by analyzing the levels of glucose, lactate, ATP, and lactate dehydrogenase (LDH) activity. Platelet aggregations induced by arachidonate and ristocetin were analyzed by aggregometer. Platelet mitochondrial melablolic activity was measured by tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay; platelet count and mean platelet volume were also determined by a hematology analyzer during 5 days of PC storage. The results indicated that LC could significantly decrease lactate concentration and glucose consumption accompanied with the increased oxygen consumption in stored PC. LDH activity also less significantly increased in LC-treated PC on days 2 and 5 of storage. Platelet aggregation in response to the ristocetin and arachidonate was significantly higher in LC-treated PC than that in untreated PC on day 5 of storage. Finally, platelet mitochondrial metabolic activity less significantly decreased in LC-treated PC compared to the control group on days 2 and 5 of storage. It seems that LC would be a good additive to reduce PSL and improve the platelet metabolism and quality of the stored PC for platelet transfusion therapy.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Carnitine deficiency and its related diseases%肉碱缺乏及其相关疾病的研究进展

    Institute of Scientific and Technical Information of China (English)

    房玥晖; 蔡美琴

    2009-01-01

    L-carnitine plays an essential role in the beta-oxidation of fatty acids by transporting long chain acyl-coenzyme A into the mitochondrial matrix.Carnitine deficiency may lead to various diseases,including lipid storage myopathies,systemic carnitine deficiency syndrome,cardiomyopathy,obesity,and infertility.This article summarizes the causes of carnitine deficiency and elucidates the clinical features and treatment strategies of its related diseases.%肉碱是脂肪β-氧化过程中长链脂酰辅酶A透过线粒体内膜时的转运体,其缺乏导致脂质沉积性肌病、全身肉碱缺乏综合征、心肌病、肥胖、男性不育等疾病.本文主要综述肉碱缺乏的原因及所导致的相关疾病的主要临床表现和治疗手段.

  3. 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....

  4. 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.

  5. Microwave-assisted extraction and quantitative LC/ID-MS measurement of total choline and free carnitine in food standard reference materials.

    Science.gov (United States)

    Phillips, Melissa M; Sander, Lane C

    2012-01-01

    The Stakeholder Panel on Infant Formula and Adult Nutritionals of AOAC INTERNATIONAL has declared both choline and carnitine to be priority nutrients in infant formulas, and ongoing efforts exist to develop or improve Official Methods of Analysis for these nutrients. As a result, matrix-based certified reference materials are needed with assigned values for these compounds. In this work, traditional acid and enzymatic hydrolysis procedures were compared to microwave-assisted acid hydrolysis, and conditions optimized to provide complete sample hydrolysis and recovery of total choline from four food standard reference materials (SRMs): whole milk powder, whole egg powder, infant formula, and soy flour. The extracts were analyzed using LC on a mixed-mode column (simultaneous RP and ion exchange) with isotope dilution-MS detection to achieve simultaneous quantification of total choline and free carnitine. Total choline has been determined in these four food matrixes with excellent precision (0.65 to 2.60%) and accuracy, as confirmed by use of SRM 1849 Infant/Adult Nutritional Formula as a control material. Free carnitine has been determined in two of these food matrixes with excellent precision (0.69 to 2.19%) and accuracy, as confirmed by use of SRM 1849 Infant/Adult Nutritional Formula as a control material. Limitations in simultaneous determination of total choline and free carnitine resulted from extreme differences in concentration of the two components in egg powder and soy flour (at least three orders of magnitude). Samples required dilution to prevent poor LC peak shape, which caused decreased precision in the determination of low concentrations of free carnitine. Despite this limitation, the described method yields results comparable to current AOAC Official Method 999.14 Choline in Infant Formula, with a decrease of more than 2 h in sample preparation time. PMID:23175983

  6. 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.

  7. 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.)

  8. 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)

    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 Ni2+-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 [3H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The Km for carnitine was 36 μM. [3H]carnitine transport was inhibited by carnitine analogues and some Cys and NH2 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.

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

    Directory of Open Access Journals (Sweden)

    Giuseppe D’Antona

    2014-01-01

    Full Text Available 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.

  10. Identification of Cyclopropylacetyl-(R)-carnitine, a Unique Chemical Marker of the Fatally Toxic Mushroom Russula subnigricans.

    Science.gov (United States)

    Matsuura, Masanori; Kato, Suguru; Saikawa, Yoko; Nakata, Masaya; Hashimoto, Kimiko

    2016-01-01

    A toxic mushroom, Russula subnigricans, causes fatal poisoning by mistaken ingestion. In spite of the potent bioactivity, the responsible toxin had not been identified for about 50 years since its first documentation. Recently, we isolated an unstable toxin and determined the structure. The slow elucidation was partly due to the instability of the toxin and also due to misidentification of R. subnigricans for similar mushrooms. To discriminate genuine Russula subnigricans from similar unidentified Russula species, we searched for a unique chemical marker contained in the mushroom. Cyclopropylacetyl-(R)-carnitine specific to R. subnigricans was identified as a novel compound whose (1)H-NMR signals appearing in the upfield region were easily recognizable among the complicated signals of the crude extract. PMID:27250795

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

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Merra; Giovanni Gasbarrini; Lucrezia Laterza; Marco Pizzoferrato; Andrea Poscia; Franco Scaldaferri; Vincenzo Arena

    2012-01-01

    AIM:To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease.METHODS: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.RESULTS: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 < 0.01) after treatment.Only patients with UC showed a significant reduction of DAI,from a median 6.5 (IQR:4-9) before treatment to 2(IQR:1-3) after treatment (P < 0.01).Conversely,in CD patients,although displaying a clear reduction of DAI from 7 (IQR:5.5-7.5) before therapy to 1.5 (IQR:0

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Hongbiao Huang

    Full Text Available 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.

  14. Determination of carnitine and acylcarnitines in urine by high-performance liquid chromatography-electrospray ionization ion trap tandem mass spectrometry.

    Science.gov (United States)

    Vernez, Laurence; Hopfgartner, Gérard; Wenk, Markus; Krähenbühl, Stephan

    2003-01-17

    A high-performance liquid chromatography-mass spectrometry method has been developed for the simultaneous determination of native carnitine and eight acylcarnitines in urine. The procedure uses a solid-phase extraction on a cation-exchange column and the separation is performed without derivatization within 17 min on a reversed-phase C8 column in the presence of a volatile ion-pairing reagent. The detector was an ion trap mass spectrometer and quantification was carried out in the MS-MS mode. Validation was done for aqueous standards at ranges between 0.75 and 200 micromol/l, depending on the compound. Carnitine was quantified in urine and comparison with a radioenzymatic assay gave a satisfactory correlation (R2 = 0.981). The assay could be successfully applied to the diagnostic of pathological acylcarnitines profile of metabolic disorders in urines of patients suffering from different organic acidurias. PMID:12564691

  15. Effects of l-carnitine and/or maize distillers dried grains with solubles in diets of gestating and lactating sows on the intestinal barrier functions of their offspring.

    Science.gov (United States)

    Wei, Bingdong; Nie, Shaoping; Meng, Qingwei; Qu, Zhe; Shan, Anshan; Chen, Zhihui

    2016-08-01

    The objective of this study was to investigate the effects of l-carnitine and/or maize distillers dried grains with solubles (DDGS) in diets of gestating and lactating sows on the intestinal barrier functions of their offspring. The experiment was designed as a 2×2 factorial with two dietary treatments (soyabean meal v. DDGS) and two l-carnitine levels (0 v. 100 mg/kg in gestating diets and 0 v. 200 mg/kg in lactating diets). Sows (Landrace×Large White) with an average parity of 4·2 with similar body weight were randomly assigned to four groups of thirty each. Dietary supplementation with l-carnitine increased the total superoxide dismutase activity but decreased the concentration of malondialdehyde of the jejunal mucosa in newborn piglets and weaning piglets on day 21. Dietary supplementation with l-carnitine decreased the concentrations of IL-1β, IL-12 and TNF-α in the jejunal mucosa of newborn piglets and decreased the concentrations of IL-6 and TNF-α in the jejunal mucosa of weaning piglets on day 21. There was an interaction between dietary treatment and l-carnitine on the bacterial numbers of total eubacteria in the digesta of caecum in weaning piglets on day 21. Bacterial numbers of total eubacteria in weaning piglets on day 21 were significantly increased by l-carnitine only in soyabean meal diet, but there was no significant effect of l-carnitine in DDGS-based diet. Dietary supplementation with l-carnitine increased the bacterial numbers of Lactobacillus spp. and bifidobacteria spp. in the digesta of caecum in weaning piglets on day 21. Dietary supplementation with l-carnitine in sows affected the expression of tight junction proteins (claudin 1, zonula occludens-1 (ZO-1) and occludin) in the jejunal mucosa of their offspring by increasing the expression of ZO-1 mRNA in the jejunal mucosa of newborn piglets, and by increasing the expression of ZO-1 and occludin mRNA in the jejunal mucosa of weaning piglets on day 21. In conclusion, dietary

  16. Effects of Dietary L-carnitine and Betaine on Serum Biochemical Indices of Large Yellow Croaker (Pseudosciaena crocea Cultured in Floating Net Cages

    Directory of Open Access Journals (Sweden)

    Wei-guo Sang

    2012-10-01

    Full Text Available The objective of this study was to investigate the biochemical changes of large yellow croaker as affected by dietary supplements. Large yellow croaker (Pseudosciaena crocea is a marine species that is widely cultured in China due to its high commercial value. However, the cage-cultured large yellow croakers were found to be less tasty compared with wild large yellow croakers due to high lipid in their body, which significantly impacts the commercial markets. Triglycerides, cholesterol and free fatty acids are main lipid ingredients in the animal body. The fish were fed with basal diet or basal diet supplemented with L-carnitine (0.08% of dry weight diet or betaine (0.8% of dry weight diet for 12 weeks in seawater floating net cages (3×2×1.5 m each holding 60 fishes. Three net cages were assigned to each dietary treatment, as replications. The seawater temperature ranged from 18 to 31°C and salinity from 25 to 28 g/kg. Fish were hand-fed one of the experimental diets to apparent satiety twice daily (05:00 and 17:30 throughout the 12 week experimental period. The results indicate that L-carnitine or betaine in diets significantly reduced Serum Triglyceride (STG and Serum Cholesterol (SCH levels while increased Serum Free Fatty Acids (SFFA content (p<0.05. The diets of L-carnitine or betaine supplements on serum biochemical indices of that fish species have positive effects. These results suggested that the supplementation with L-carnitine or betaine is one of the effective ways to improve the meat quality of large yellow croakers cultured in floating net cages.

  17. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    OpenAIRE

    Vuslat Yurut-Caloglu; Murat Caloglu; Sevgi Eskiocak; Ebru Tastekin; Alaattin Ozen; Nukhet Kurkcu; Fulya Oz-Puyan; Zafer Kocak; Cem Uzal

    2015-01-01

    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 irradia...

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

    Institute of Scientific and Technical Information of China (English)

    Jin-Xiu Cheng; Xing Pan; Cui-Lan Liu; Hua Liu; Sheng-Jun Liu; Ling-Ling Wang

    2016-01-01

    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.

  19. Acetyl-L-Carnitine Supplementation During HCV Therapy With Pegylated Interferon-α 2b Plus Ribavirin: Effect on Work Performance; A Randomized Clinical Trial

    OpenAIRE

    Malaguarnera, Giulia; Pennisi, Manuela; Gagliano, Caterina; Vacante, Marco; Malaguarnera, Michele; Salomone, Salvatore; Drago, Filippo; Bertino, Gaetano; Caraci, Filippo; Nunnari, Giuseppe; Malaguarnera, Mariano

    2014-01-01

    Background: The health status of employees with chronic hepatitis C has major implications for organizations and labour market. Objectives: To assess the effects of Acetyl-L-Carnitine administration on work productivity, daily activity, and fatigue in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b and Ribavirin. Patients and Methods: In this prospective, randomized, placebo controlled, double blind clinical trial, 30 subjects (Group A) with chronic hepatitis, received...

  20. 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.

  1. Induction of PDK4 in the heart muscle of JVS mice, an animal model of systemic carnitine deficiency, does not appear to reduce glucose utilization by the heart.

    Science.gov (United States)

    Ushikai, Miharu; Horiuchi, Masahisa; Kobayashi, Keiko; Matuda, Sadayuki; Inui, Akio; Takeuchi, Toru; Saheki, Takeyori

    2011-03-01

    Pyruvate dehydrogenase kinase 4 (PDK4) mRNA has been reported as an up-regulated gene in the heart and skeletal muscle of carnitine-deficient juvenile visceral steatosis (JVS) mice under fed conditions. PDK4 plays an important role in the inhibition of glucose oxidation via the phosphorylation of pyruvate dehydrogenase complex (PDC). This study evaluated the meaning of increased PDK4 mRNA in glucose metabolism by investigating PDK4 protein levels, PDC activity and glucose uptake by the heart and skeletal muscle of JVS mice. PDK4 protein levels in the heart and skeletal muscle of fed JVS mice were increased in accordance with mRNA levels, and protein was enriched in the mitochondria. PDK4 protein was co-fractionated with PDC in sucrose density gradient centrifugation, like PDK2 protein; however, the activities of the pyruvate dehydrogenase complex (PDC) active form in the heart and skeletal muscle of fed JVS mice were similar to those in fed control mice. Fed JVS mice showed significantly higher glucose uptake in the heart and similar uptake in the skeletal muscle compared with fed control mice. Thus, in carnitine deficiency under fed conditions, glucose was preferentially utilized in the heart as an energy source despite increased PDK4 protein levels in the mitochondria. The preferred glucose utilization may be involved in developing cardiac hypertrophy from carnitine deficiency in fatty acid oxidation abnormality. PMID:21190881

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

    International Nuclear Information System (INIS)

    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. 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.

  4. 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.

  5. Quantitative analysis of the dynamic signaling pathway involved in the cAMP mediated induction of l-carnitine biosynthesis in E. coli cultures.

    Science.gov (United States)

    Hormiga, José; González-Alcón, Carlos; Sevilla, Angel; Cánovas, Manuel; Torres, Néstor V

    2010-04-01

    L-(-)-carnitine can be synthesized from waste bioprecursors in the form of crotonobetaine. Such biotransformation is carried out in E. coli by the enzymes encoded by operons regulated by the cAMP receptor proteins. Non-phosphorylated sugars, such as glycerol are used as energy and carbon source since glucose inhibits cAMP synthesis. Until now little attention has been paid to the regulatory signaling structure that operates during the transition from a glucose-consuming, non-l-carnitine producing steady state, to a glycerol-consuming l-carnitine producing steady state. In this work we aim to elucidate and quantify the underlying regulatory mechanisms operating in the abolition of the glucose inhibiting effect. For this purpose we make use of the systemic approach by integrating the available information and our own experimentally generated data to construct a mathematical model. The model is built using power-law representation and is used as a platform to make predictive simulations and to assess the consistency of the regulatory structure of the overall process. The model is subsequently checked for quality through stability and a special, dynamic sensitivity analysis. The results show that the model is able to deal with the observed system transient phase. The model is multi-hierarchical, comprising the metabolic, gene expression, signaling and bioreactor levels. It involves variables and parameters of a very different nature that develop in different time scales and orders of magnitude. Some of the most relevant conclusions obtained are: (i) the regulatory interactions among glucose, glycerol and cAMP metabolism are far stronger than those present in the l-carnitine transport, production and degradation processes; (ii) carnitine biosynthesis is very sensitive to the cAMP signaling system since it reacts at very low cAMP receptor concentrations, and (iii) ATP is a critical factor in the transient dynamics. All these model-derived observations have been

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

    Directory of Open Access Journals (Sweden)

    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

  7. Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.

    Science.gov (United States)

    Kocsis, Kitti; Frank, Rita; Szabó, József; Knapp, Levente; Kis, Zsolt; Farkas, Tamás; Vécsei, László; Toldi, József

    2016-09-22

    Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500μM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment. PMID:27378558

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Ergogenic effect of dietary L-carnitine and fat supplementation against exercise induced physical fatigue in Wistar rats.

    Science.gov (United States)

    Pandareesh, M D; Anand, T

    2013-12-01

    L-carnitine (LC) plays a central role in fatty acid metabolism and in skeletal muscle bioenergetics. LC supplementation is known to improve physical performance and has become widespread in recent years without any unequivocal support to this practice. A scientific-based knowledge is needed, to understand the implications of LC supplementation on physical fatigue. In current study, we have explored synergistic effects of dietary LC and fat content against physical fatigue in rats. Ninety male Wistar rats were supplemented with different concentrations of LC (0.15, 0.3, and 0.5 %) and fat content (5, 10, and 15 %) through diet in different combinations. Our results elucidated that LC (0.5 %) along with 10 and 15 % fat diet supplemented rats showed significant ergogenic effect. The swimming time until exhaustion was increased by ~2- and ~1.5-fold in rats fed with 10 and 15 % fat diet containing LC (0.5 %). LC supplementation improved the energy charge by increasing the levels of ATP, tissue glycogen, reduced GSH, plasma triglyceride, plasma glucose levels, and enzymatic antioxidant status, i.e., superoxide dismutase, catalase, and glutathione peroxidase. LC supplementation also significantly reduced lipid peroxidation, lactic acid, plasma urea nitrogen, creatinine, creatinekinase, and lactate dehydrogenase levels in various tissues compared to its respective control group. Thus the present study indicates that LC ameliorates the various impairments associated with physical endurance in rats. PMID:23661316

  10. 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

    The isobutyryl-CoA dehydrogenase (IBD) enzyme is involved in the degradation of valine. IBD deficiency was first reported in 1998 and subsequent genetic investigations identified acyl-CoA dehydrogenase (ACAD) 8, now IBD, as the gene responsible for IBD deficiency. Only three individuals homozygous...... 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......-glycine, and in vitro probe analysis of fibroblasts from two newborns indicated enzymatic IBD defect. Molecular genetic analysis revealed seven new rare variations in the IBD gene (c.348C>A, c.400G>T, c.409G>A, c.455T>C, c.958G>A, c.1000C>T and c.1154G>A). Furthermore, sequence analysis of the short-chain acyl...

  11. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Effects of Oral L-Carnitine Supplementation on Lipid Profile, Anemia, and Quality of Life in Chronic Renal Disease Patients under Hemodialysis: A Randomized, Double-Blinded, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Afsoon Emami Naini

    2012-01-01

    Full Text Available In patients on maintenance hemodialysis several factors reduce the body stored carnitine which could lead to dyslipidemia, anemia, and general health in these patients. We evaluated the effect of oral L-carnitine supplementation on lipid profiles, anemia, and quality of life (QOL in hemodialysis patients. In a randomized, double-blinded, placebo-controlled trial, end-stage renal disease (ESRD patients on hemodialysis received either L-carnitine 1 g/d (n=24 or placebo (27 patients for 16 weeks. At the end of the study, there was a significant decrease in triglyceride (-31.1±38.7 mg/dL, P=0.001 and a significant increase in HDL (3.7±2.8 mg/dL, P0.05. Erythropoietin dose was significantly decreased in both the carnitine (-4750±5772 mg, P=0.001 and the placebo group (-2000±4296 mg, P<0.05. No improvement was observed in QOL scores of two groups. In ESRD patients under maintenance hemodialysis, oral L-carnitine supplementation may reduce triglyceride and cholesterol and increase HDL and hemoglobin and subsequently reduce needed erythropoietin dose without effect on QOL.

  16. Selective inhibition of OCTN2 is more effective than inhibition of gamma-butyrobetaine dioxygenase to decrease the availability of l-carnitine and to reduce myocardial infarct size.

    Science.gov (United States)

    Liepinsh, Edgars; Makrecka, Marina; Kuka, Janis; Cirule, Helena; Makarova, Elina; Sevostjanovs, Eduards; Grinberga, Solveiga; Vilskersts, Reinis; Lola, Daina; Loza, Einars; Stonans, Ilmars; Pugovics, Osvalds; Dambrova, Maija

    2014-07-01

    l-Carnitine is a cofactor in the energy metabolism pathways where it drives the uptake and oxidation of long chain fatty acids (LCFA) by mitochondria. LCFA lipotoxicity causes mitochondrial damage and results in an insufficient energy supply and a decrease in l-carnitine content limits LCFA flux and protects mitochondria. Here, we tested whether the inhibition of GBB dioxygenase (BBOX) or organic cation transporter 2 (OCTN2) is the most effective strategy to decrease l-carnitine content. The activity of 51 compounds was tested and we identified selective inhibitors of OCTN2. In contrast to selective inhibitors of BBOX, OCTN2 inhibitors induced a 10-fold decrease in l-carnitine content in the heart tissues and a significant 35% reduction of myocardial infarct size. In addition, OCTN2 inhibition correlated with the inhibitor content in the heart tissues, and OCTN2 could potentially be an efficient target to increase drug transport into tissues and to reduce drug elimination by urine. In conclusion, the results of this study confirm that selective inhibition of OCTN2, compared to selective inhibition of BBOX, is a far more effective approach to decrease l-carnitine content and to induce cardioprotective effects. OCTN2 could potentially be an efficient tool to increase drug transport in tissues and to reduce drug elimination via urine. PMID:24836867

  17. The Effects of Different Levels of Dietary Protein and L-Carnitine on Blood Sugar and Lipids of the New GIFT Strain of Juvenile Nile Tilapia (Oreochromis niloticus)

    OpenAIRE

    Gang Chen; Minghui Zhang; Jiandong Zhang; Hongbiao Dong; Hui Zhou; Baogui Tang; Jiansheng Huang; Gang Shi; Ling Jiang; Zhaohe Wu

    2009-01-01

    The new GIFT (Genetically Improved Farmed Tilapia) strain of Nile tilapia is a popular cultivated fish in Asia, but intensive aquaculture using nutritionally imbalanced feed has led to disorder of lipid metabolisms. An 8-week feeding experiment was conducted in order to assess the effects of different levels of L-carnitine (0, 200, 400, 600, and 800 mg/kg) and dietary protein (22, 25, and 28%) on blood sugar and blood lipid contents of the new juvenile GIFT strain of Nile tilapia. Results sho...

  18. Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial

    OpenAIRE

    OZTURK, MEHMET ADNAN; KARDAS, ZEHRA; KARDAS, FATİH; GUNES, TAMER; KURTOGLU, SELİM

    2015-01-01

    The aim of the present study was to investigate the efficacy of L-carnitine therapy on the occurrence and prognosis of respiratory distress syndrome (RDS). A single blind, randomized controlled trial study was conducted on 130 infants with gestational ages of 28–36 weeks. Infants were assigned to experimental groups (groups 1 and 2) and control groups (groups 3 and 4). Groups 1 and 3 consisted of infants with RDS, and groups 2 and 4 groups were composed of infants without RDS. The experimenta...

  19. Primary carnitine deficiency in 17 patients: diagnosis, treatment and follow up%原发性肉碱缺乏症17例诊治与随访

    Institute of Scientific and Technical Information of China (English)

    韩连书; 顾学范; 叶军; 邱文娟; 张惠文; 王瑜; 季文君; 高晓岚; 李晓燕; 金晶

    2012-01-01

    目的 探讨原发性肉碱缺乏症的诊断与治疗.方法 利用串联质谱技术对27万例新生儿和1.2万例临床遗传代谢病疑似患儿进行游离肉碱及酰基肉碱检测,对游离肉碱降低的患儿进行肉碱转运蛋白基因突变检测确诊.对确诊患儿给予左旋肉碱治疗,100~300 mg/(kg·d),分3次静滴或口服.随访时间3个月~3年.结果 共确诊17例原发性肉碱缺乏症患儿,其中6例来自新生儿筛查,11例来自临床患儿.17例患儿均检测到基因突变.患儿血游离肉碱水平[(2.85±1.87)μmol/L]低于参考值(10 μmol/L),伴不同种类的酰基肉碱水平下降.治疗随访14例,给予左旋肉碱治疗1~3个月后,临床症状消失,血游离肉碱升至正常,由(2.91±2.01) μmol/L升至(20.63±8.32)μmol/L,其他酰基肉碱也升至正常.结论 采用串联质谱技术检测血游离肉碱、酰基肉碱水平及肉碱转运蛋白基因检测诊断了17例原发性肉碱缺乏症患儿,其中14例患儿经大剂量左旋肉碱治疗获得了较好的疗效.%Objective Many children were found to have low free carnitine level in blood by tandem mass spectrometry technology.In some of the cases the problems occurred secondary to malnutrition,organic acidemia and other fatty acid oxidation metabolic diseases,and some of cases had primary carnitine deficiency (PCD).In the present article,we discuss the diagnosis of PCD and evaluate the efficacy of carnitine in the treatment of PCD.Method We measured the free carnitine (CO) and acylcarnitine levels in the blood of 270 000 neonates from newborns screening program and 12 000 children with suspected clinical inherited metabolic diseases by tandem mass spectrometry.The mutations of carnitine transporter protein were tested to the children with low CO level and the diagnosis was made.The children with PCD were treated with 100-300 mg/kg of carnitine.Result Seventeen children were diagnosed with PCD,6 from newborn screening program and 11 from

  20. Effects on the Human Body of a Dietary Supplement Containing L-Carnitine and Garcinia cambogia Extract: A Study using Double-blind Tests

    OpenAIRE

    Yonei, Yoshikazu; Takahashi, Yoko; Hibino, Sawako; Watanabe, Miwako; Yoshioka, Toshito

    2008-01-01

    The effect of a dietary supplement with L-carnitine (600 mg/day) and Garcinia cambogia extract (500 mg/day as hydroxycitric acid) as main ingredients was studied in 35 healthy volunteers {48.3 ± 6.9 years, body mass index (BMI): 26.3 ± 1.7} in a double-blind test (18 subjects in the Test Group and 17 in the Control Group). The yearly examination includes the standard yearly medical tests done in Japan, tests for assessing hormonal age, and a survey for assessing physical and mental fitness of...

  1. 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. PMID:26918530

  2. 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.

  3. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    International Nuclear Information System (INIS)

    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

  4. 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.

  5. 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.

  6. Novel Mutations in the CPT1A Gene Identified in the Patient Presenting Jaundice as the First Manifestation of Carnitine Palmitoyltransferase 1A Deficiency.

    Science.gov (United States)

    Choi, Jong Sub; Yoo, Hyeoh Won; Lee, Kyung Jae; Ko, Jung Min; Moon, Jin Soo; Ko, Jae Sung

    2016-03-01

    Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme functioning in mitochondrial fatty acid oxidation (FAO) of the liver. Patients with CPT1A deficiency have impaired mitochondrial FAO and display hypoketotic hypoglycemia and hepatic encephalopathy as typical manifestations. In this report, we present a case of CPT1A deficiency presenting jaundice as the first manifestation. A 1.9 years old boy showed jaundice and elevated levels of free and total carnitine were observed. From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified. At the age of 2.2 years, hypoglycemia, tachycardia, and altered mental status developed just after cranioplasty for craniosynostosis. High glucose infusion rate was required for recovery of his vital signs and mentality. Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date. PMID:27066452

  7. Impact of L-Carnitine and Cinnamon on Insulin-Like Growth Factor-1 and Inducible Nitric Oxide Synthase Gene Expression in Heart and Brain of Insulin Resistant Rats

    Directory of Open Access Journals (Sweden)

    Mona A. Mohamed

    2010-01-01

    Full Text Available Problem statement: Evaluate the effects of daily administration of L-carnitine and cinnamon extract for two weeks on the expression of Insulin-like Growth Factor-1 (IGF-1 and inducible Nitric Oxide Synthase (iNOS genes in cardiac and brain tissues of rats with Insulin Resistance (IR. Approach: Rats were divided into 4 groups (8 animals each: Group (1 rats fed control diet (60% starch as control while groups (2, 3 and 4 fed high fructose diet (60% fructose. At the beginning of the 3rd week of feeding, rats of group (3 were treated with L-carnitine (300 mg kg-1 body weight/day, i.p. and animals of group (4 received a daily oral dose of cinnamon aqueous extract (0.5 mL rat-1. The animals were maintained in their respective groups for 4 weeks. Results: Feeding high fructose diet causes significant reduction in Insulin Receptor Substrate-1 (IRS-1 (amounted 30.65% and elevation in iNOS expression (reached 51% in the cardiac tissues as compared to control. In brain tissues, the IGF-1 mRNA was reduced in fructose loaded groups (28.81%. Administration of either L-carnitine or cinnamon extract significantly improves the expression of the cardiac studied genes but with no effects on the brain tissues. Conclusion: The present study illustrated that CE was more potent than L-carnitine in improving the IR.

  8. Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics

    Directory of Open Access Journals (Sweden)

    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

  9. Histopathological and electrophysiological indices of rotenone-evoked dopaminergic toxicity: Neuroprotective effects of acetyl-L-carnitine.

    Science.gov (United States)

    Sarkar, S; Gough, B; Raymick, J; Beaudoin, M A; Ali, S F; Virmani, A; Binienda, Z K

    2015-10-01

    Exposure to the natural pesticide, rotenone, a potent mitochondrial toxin, leads to degeneration in striatal nerve terminals and nigral neurons. Rotenone-induced behavioral, neurochemical and neuropathological changes in rats mimic those observed in Parkinson's disease (PD). Here, protective effects of acetyl-L-carnitine (ALC) in the brain dopaminergic toxicity after a prolonged exposure to rotenone were evaluated using electrophysiological and immunolabeling methods. Adult, male Sprague-Dawley rats were injected i.p. with rotenone alone (1 mg/kg) or rotenone with ALC (either 10 or 100 mg/kg; ALC10 or ALC100, respectively) once daily on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33 and 37. Control rats received either 100mg/kg ALC or vehicle (30% Solutol HS 15 in 0.9% saline) injections. Animals were weighed on injection days and monitored daily. Motor nerve conduction velocity (MCV) was assessed within two days after treatment using compound muscle action potentials (CMAP) detected from the tail muscle through surface receiver electrodes installed around the distal part of the tail. Rats were perfused immediately after testing with 4% paraformaldehyde and immunohistochemical analysis of dopamine transporter (DAT), tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and microglial CD11b marker was performed in the caudate-putamen (CPu) and the substantia nigra pars compacta (SNc) in order to estimate dopaminergic neuronal and transporter damage. Additionally, effects of ALC on preventing microglial or astrocytic hypertrophy were also evaluated. In rats exposed to rotenone and rotenone/ACL10, a significant increases in both proximal (S1) and distal (S2) motor latency and a decrease in MCV were detected in tail nerves (p<0.05). The conduction parameters in rats co-treated with rotenone/ACL100 were not different from control. It was found that 100 mg/kg ALC prevented loss of TH and a decline of DAT level in the midbrain and also prevented

  10. Empirical study on anti-fatigue effect of L-Carnitine%左旋肉碱抗疲劳实验研究

    Institute of Scientific and Technical Information of China (English)

    周筱燕; 陈静; 刘常秀; 李伟; 吴伟青; 刘超群

    2011-01-01

    目的 研究左旋肉碱抗疲劳的效果.方法 将健康雄性昆明小鼠80只随机分入四个组:实验前肌糖原和肝糖原测定组、负重游泳组、血乳酸测定组、尿素氮测定组,每个实验各20只小鼠.每个组再随机分成对照组和实验组,每组10只.对照组每天以蒸馏水灌胃,实验组以600mg/kg左旋肉碱灌胃,连续6周后分别测定肝糖原、肌糖原、游泳时间、血乳酸、血清尿素氮含量等指标,观察左旋肉碱抗疲劳效果.结果 左旋肉碱组小鼠游泳时间和运动前肌肝糖原含量较对照组明显增加(P0.05);运动后左旋肉碱组乳酸增加较对照组明显降低(P0.05),但休息120min后,左旋肉碱组血清尿素氮含量较对照组明显降低,恢复率显著增高(P<0.05).结论 左旋肉碱具有抗疲劳作用,其抗疲劳作用机理主要与左旋肉碱增加肌肝糖原储备,减少运动后肌肝糖原消耗,抑制乳酸生成.加速乳酸和尿素氮清除有关.%Objective To study the anti-fatigue effect of L-Carnitine. Methods 80 KM mice were randomly divided for 4experimental studies (20 mice / experiment), namely the hepatic and muscle glycogen test, adopted weight loading swimming test, serum lactic acid test and serum urea nitrogen contents test. In each experiment, the mice were randomly divided into 2groups ( 10/group), namely the control group and the treatment group. Mice in the treatment group were fed with 600 mg/kg of L-Carnitine for 6 weeks, and the mice in the control group were fed with distilled water. Swimming time, hepatic glycogen,mnsele glycogen, serum lactic acid, serum urea nitrogen contents were measured. Results The swimming time of the L-Carnitine treatment group was prolonged significantly (P<0.05). Before the swimming test, hepatic and muscle glycogen contents in the treatment group were higher than the control group (P<0.05). The rate of consumption of hepatic glycogen after swimming for 30 minutes and the rate of

  11. Modelling and analysis of central metabolism operating regulatory interactions in salt stress conditions in a L-carnitine overproducing E. coli strain.

    Directory of Open Access Journals (Sweden)

    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

  12. 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

    MaternalmRNA governs earlyembryonic development in fish and variation in abundance of maternal transcripts may contribute to variation in embryonic survival and hatch success in European eel, Anguilla anguilla. Previous studies have shown that quantities of the maternal gene products β......-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...... these genes in European eel after the mid-blastula transition, may be needed to sustain embryonic development and hatching success...

  13. Application of the antioxidant of L-carnitine in IVF cycles%抗氧化剂左卡尼汀在IVF中的应用

    Institute of Scientific and Technical Information of China (English)

    黄映琴; 覃爱平; 孙惟佳; 靳玉甫; 李柳铭; 欧奇志

    2013-01-01

    Objective To invetigate the efficacy of a treatment with antioxidant of L-carnitine in women undergoing in vitro fertilization (IVF) cycles. Methods One hundred and thirty women undergoing first IVF cycles in our center were analyzed from May to September 2011. All women were randomized into the control group and the study group. Women in the study group (n = 57) received L-carnitine, but women in the control group (n = 73) didn't received L-carnitine. Clinical effects of women in these two groups were compared. Results The level of estradiol (E2) on the day of hCG injection, number of fertilization, number of embryo cleavage , number of perfect embryos and total number of embryos available in the study group were higher than those in the control group (P < 0.05), but no significant difference in total number of oocytes retrieved, biochemical pregnancy rate, implantation rate, pregnant rate and abortion rate was found between these two groups. Significant increases in the level of estradiol (E2) on the day of hCG injection, number of fertilization, number of embryo cleavage , number of perfect embryos and total number of embryos available were shown in the women younger than 35 years old, not in those older than 35 years old, in the study group compared to those in the control group (P< 0.05, respectively). Conclusions L-carnitine could improve oocyte quality, enhance the number of mature oocytes, and increase the number of early embryonic formation and blastocyst development in some women, especially for the women younger than 35 years old.%目的:探讨抗氧化剂左卡尼汀在IVF-ET治疗中的临床疗效.方法:选择2011年5月至2011年9月在我院生殖中心初次行IVF治疗者130例,随机分为两组.左卡尼汀(L-camitine)用药组为研究组(57例),非用药组为对照组(73例).比较两组的临床结局情况.结果:研究组在HCG日的E2水平、受精数、卵裂数、优质胚胎数、可移植胚胎数均高于对照

  14. Research advances of carnitine palmitoyltransferase 1A%肉毒碱棕榈酰基转移酶1A的研究进展

    Institute of Scientific and Technical Information of China (English)

    魏婷; 张永煜; 张庆华

    2013-01-01

    在真核生物的脂肪酸代谢过程中,肉毒碱棕榈酰基转移酶(carnitine palmitoyltransfersse 1A,CPT1A)是长链脂肪酸由胞浆转移到线粒体氧化供能的关键限速酶.CPT1A基因可受到体内多种转录因子、激素以及代谢物的调节,同时影响相关代谢类疾病的发生发展,是疾病治疗和药物开发的新靶点和热点.全面综述了CPT1A基因在生理过程中的作用和调节,与疾病的相互关系以及相关药物的研究进展.%The majority of fatty acid β-oxidation occurs in mitochondria and is controlled by carnitine palmitoyltransferase 1A (CPT1A),which is a key regulator to facilitate the transfer of long-chain fatty acids across the mitochondrial membrane for β-oxidation in mammals.A variety of biologic compounds can regulate the activity of CPT1A and this regulation may influence the evolvement of several metabolic diseases.However,the transformation of CPT1A could bring new possibilities to researches and develop therapies and medicines for those related diseases.This paper mainly reviews the research progress of CPT1A's effect and regulation in the life progression and the development of the related diseases and pharmacies of CPT 1A.

  15. Genetic deficiency of carnitine/organic cation transporter 2 (slc22a5) is associated with altered tissue distribution of its substrate pyrilamine in mice.

    Science.gov (United States)

    Kato, Sayaka; Kato, Yukio; Nakamura, Tadakatsu; Sugiura, Tomoko; Kubo, Yoshiyuki; Deguchi, Yoshiharu; Tsuji, Akira

    2009-12-01

    Carnitine/organic cation transporter 2 (OCTN2) recognizes various cationic compounds as substrates in vitro, but information on its pharmacokinetic role in vivo is quite limited. This paper demonstrates altered tissue distribution of the OCTN2 substrate pyrilamine in juvenile visceral steatosis (jvs) mice, which have a hereditary defect of the octn2 gene. At 30 min after intravenous injection of pyrilamine, the tissue-to-plasma concentration ratio (K(p)) in the heart and pancreas was higher, whereas the K(p) in kidney and testis was lower in jvs mice compared with wild-type mice. Pyrilamine transport studies in isolated heart slices confirmed higher accumulation, together with lower efflux, of pyrilamine in the heart of jvs mice. The higher accumulation in heart slices of jvs mice was abolished by lowering the temperature, by increasing the substrate concentration, and in the presence of other H(1) antagonists or another OCTN2 substrate, carnitine, suggesting that OCTN2 extrudes pyrilamine from heart tissue. On the other hand, the lower distribution to the kidney of jvs mice was probably due to down-regulation of a basolateral transporter coupled with OCTN2, because, in jvs mice, (i) the K(p) of pyrilamine in kidney assessed immediately after intravenous injection (approximately 1 min) was also lower, (ii) the urinary excretion of pyrilamine was lower, and (iii) the uptake of pyrilamine in kidney slices was lower. The renal uptake of pyrilamine was saturable (K(m) approximately 236 microM) and was strongly inhibited by cyproheptadine, astemizole, ebastine and terfenadine. The present study thus indicates that genetic deficiency of octn2 alters pyrilamine disposition tissue-dependently. PMID:19821448

  16. Effect of L-carnitine and Hoodia gordonii Supplementation on Metabolic Markers and Physical Performance under Short Term Calorie Restriction in Rats

    Directory of Open Access Journals (Sweden)

    Swati Jain

    2016-01-01

    Full Text Available Calorie restriction can occur as a consequence of food shortage due to natural calamities, war like situations or voluntarily for health benefits. This state of negative energy balance leads to decrease in performance and increase in feeling of hunger. A normal individual can sustain himself on stored energy in form of body fat for a period of time. It was hypothesised that use of an appetite suppressant like Hoodia gordonii along with L-carnintine, which helps in fat oxidation can be used as strategy for coping adverse situation without compromising physical performance. The aim of the study was to evaluate the combined effect of H. gordonii and L-carnitine supplementation on metabolic changes and appetite regulatory peptides during calorie restriction. Male albino rats were divided into two groups (n=12 in each i.e. control (without treatment and treated (H. gordonii organic solvent extract and L-carnitine, orally for 5 days at a dose of 100 mg/kg under 25 per cent calorie restriction. Biochemical variables including regulatory peptides were estimated along with physical efficiency tests. Significant changes in ghrelin, leptin, corticosterone and thyroid hormones were observed in comparison to control. While blood glucose, AMP kinase decreased significantly in the treated group, an increase in CPT-1 activity was observed compared with controls. It is concluded that approach could be practically suitable and effective in emergency situations of combat or food shortage.Defence Science Journal, Vol. 66, No. 1, January 2016, pp. 11-18, DOI: http://dx.doi.org/10.14429/dsj.66.9178

  17. Current Research Review on Athletic Ability and Substance Metabolism After Supplementing L-carnitine%左旋肉碱对机体物质代谢及运动能力的影响研究进展

    Institute of Scientific and Technical Information of China (English)

    刘刚; 张蕴琨

    2012-01-01

    L-肉碱(即左旋肉碱L-carnitine)是机体内一种具有多种生理功能的氨基酸类物质,对机体血浆肉碱含量、肌肉酶活性以及更为重要的脂类代谢过程具有重要的调节作用,早期的研究主要关注补充L-肉碱后可以增强机体的耐力运动表现,近十年来对于L-肉碱作为肌肉能源选择以及生理功能调节者的重要作用的研究提出了许多富有见解的新观点;L-肉碱在通过线粒体膜转运脂肪酸的过程中发挥着重要的作用,在血浆中确实发现了血浆肉碱含量增加的情况。虽然一些研究表明,相对于运动能力而言,在口服肉碱后,并没有显示出其对健康人群机体物质代谢及健康状况会产生不可或缺的影响,但是绝大多数研究表明,L-肉碱可以帮助特定的人群在运动能力表现上达到一个较高的水平。%L-carnitine is an important functional amino acid derivative,which plays an indispensable role in modulating lipid metabolism,plasma carnitine and enzyme activity in muscular tissues.Biologically,carnitine is essential for the transport of long chain fatty acids across the outer-and inner' mitochor]drial membranes.Conflicting results characterized the early research focused on L-carnitine supplementation's ability to enhance endurance performance,and studies showed no changes occurred in muscle carnitine levels.Recent studies have focused upon a different paradigm for L-carnitine in regulating hypoxic stress and enhancing recovery from exercise.However,research over the past decade has shed new light on the importance of carnitine as a regulator of skeletal muscle fuel selection and physiological function.In conclusion,manipulating the carnitine pool of skeletal muscle at rest,both physiologically and pharmacologically,has provided insight into the regulation of skeletal muscle fat and carbohydrate oxidation,both at rest and during exercise,and the interchange between anaerobic and oxidative energy

  18. Effect of L-Carnitine Supplementation in Low Methionine Diets on Broilers' Growth Performance%低蛋氨酸日粮添加L-肉碱对肉仔鸡生产性能的影响

    Institute of Scientific and Technical Information of China (English)

    李春华

    2013-01-01

    L-carnitine supplementary effects on broilers with low methionine level diets were studied in this paper. 300 Avine broilers were randomly divided into 5 groups , each group consisted of 3 repeat 20 birds each repeat. The results showed:1,The broiler's growth performance dropped when 50mg/kg L-carnitine and no methionine were supplied in low methionine diet;2, The broiler's growth performance didn't change when 100mg/kg L-carnitine and no methionine were supplied in low methionine diet;3, The broiler's growth performance improved when 50mg/kg or 100mg/kg L-carnitine and 0.05%methionine were supplied low methionine diet.%本课题研究在低蛋氨酸日粮中添加L-肉碱对肉仔鸡的影响。试验选用300只1日龄健康的艾维茵肉仔鸡,将随机分成5组,每组3个重复,每个重复20只。试验结果表明:1.低蛋氨酸日粮中添加L-肉碱50 mg/kg时不补加蛋氨酸肉仔鸡的生产性能下降;2.添加L-肉碱100 mg/kg时不补加蛋氨酸不影响肉仔鸡的生产性能;3.添加L-肉碱50mg/kg或100mg/kg时蛋氨酸补加0.05%对肉仔鸡生产性能有改善作用。

  19. 肉毒碱对全胃肠外营养大鼠肝损害的作用%Addition of carnitine to total parenteran nutrition and its effects on development of hepatic injury in rats

    Institute of Scientific and Technical Information of China (English)

    郑进方; 梁力建

    2001-01-01

    目的:探讨肉毒碱对全胃肠外营养(TPN)大鼠肝损害的影响。方法:18只Wistar大鼠随机分为3组:A组,自由进食和进水;B组,TPN;C组,TPN+肉毒碱。实验结束后测氮平衡、肝功能、肝脂及肝脏组织学检查。结果:各组大鼠体重增加,获正氮平衡。各组间肝功能无差异。B组肝内脂肪显著增加,C组肝内脂肪明显减少。结论:肉毒碱能减轻TPN引起的肝脂肪变性。%AIM: Infusion of total parenteral nutrition (TPN) can lead tohepatic steatosis. In this study we attempted to reverse the injury by adding carnitine to TPN. METHODS: Adult wistar rats received internal jugular catheters and were divided into 3 groups randomly. Group A (n=6) chowed ad libitum, Group B (n=6) TPN for 1 wk, Group C (n=6) TPN with carnitine. Nitrogen balance was determined after 7 d. Peripheral venous blood was drawn for liver function tests. Livers were removed for morphologic studies and lipid content determination. RESULTS: All the rats gained the weight and maintained in positive nitrogen balance in the study.There were no significant differences in liver function tests among all groups. Hepatic lipid content was significantly elevated and hepatic steatosis was noted in group B. Hepatic lipid content and hepatic lipid infiltration were significantly lowered when carnitine was added to the TPN solution. CONCLUSION: Carnitine can palliate TPN-induced hepatic steatosis.

  20. 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

    OpenAIRE

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    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...

  1. 左旋肉碱与代谢综合征关系的研究进展%Development of the Studies on Relationships between L-carnitine and Metabolic Syndrome

    Institute of Scientific and Technical Information of China (English)

    范晶晶; 吕超; 滕文娇

    2011-01-01

    L-carnitine is an important component of the β oxidation process of mitochondrial fatty acid.It is mainly used for cardiovascular disease, liver disease and male reproductive system diseases in clinic. Recent studies have shown that L-carnitine through promoting the decomposition of fatty acids into the mitochondria,increase in blood levels of high density lipoprotein ways to improve some major symptoms of metabolic syndrome including ohesity , dyslipidemia,cardiovascular disease and hyperglycemia. Here the relationship between L-carnitine and some major symptoms of metabolic syndrome were reviewed.%左旋肉碱是线粒体脂肪酸β氧化过程中的重要成分,临床上主要用于心血管疾病、肝病与男性生殖系统疾病的治疗.近来有研究表明,左旋肉碱通过促进脂肪酸进入线粒体氧化分解,提高血液中高密度脂蛋白水平等方式改善代谢综合征中肥胖、血脂紊乱、心血管疾病和高血糖的临床症状.现就其与代谢综合征的主要临床症状的关系的研究进展做简要综述.

  2. The effects of L-carnitine and alpha-tocopherol on acid excretion defect during the acute ureteral obstruction in anaesthetized rats

    Directory of Open Access Journals (Sweden)

    Ashtiyani SC

    2010-01-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ureteral obstruction has been shown to induce renal oxidative stress, suppressed energy metabolism and defected acid excretion. This study was aimed to examine the improving effects of L-carnitine, a facilitating cofactor for mitochondrial oxidation of fatty-acids as well as a scavenger of free-radicals, and a-tocopherol as the most potent antioxidant on these renal disorders at early hours following release of unilateral ureteral obstruction. "n"nMethods: The left ureter was ligated in 60 anaesthetised rats, L-carnitine, a-tocopherol, or their vehicles (normal saline and olive oil, respectively were injected (i.p. in four groups. Each rat was re-anesthetized and cannulated, and ureteral legation was released at exactly 24h after UUO-induction. A 30-min clearance period performed to separately collect urine from both kidneys. The collected urine and arterial blood samples were given to pH-gas analyzer and autoanalyzer, and malondialdehyde (MDA, ATP and ADP levels were assessed in preserved kidneys. There were also sham and control groups (n=8-10 in each."n"nResults: In the post-obstructed kidney of vehicle-treated groups with respect to the equivalent kidney of sham group, there were increases in MDA (p<0

  3. 比较饮食摄取l-卡尼汀和dl-卡尼汀对氨中毒和肝代谢的作用%Comparative effects of diet supplementation with l-carnitine and dl-carnitine on ammonia toxicity and hepatic metabolism in rats

    Institute of Scientific and Technical Information of China (English)

    Vilma A F G GAZOLA; Rose M M DIAS; Gisele LOPES; Rui CURI; Roberto B BAZOTTE

    2001-01-01

    AIM: To compare the effects of chronic supplementation with l-camitine (LCT) and dl-carnitine (DLC) on am monia toxicity and hepatic metabolism. METHODS: Three groups of male adult rats were studied: 1) supple mented with LCT ( 1.2 mmol· kg- 1 · d- 1 ), 2 ) supple mented with DLC ( 1.2 mmol· kg- 1· d- 1 ), and 3) con trol group (COG) not supplemented. RESULTS: The treatment with LCT decreased the toxicity to ammonia. However, the supplementation with DLC did not show any significant effect. In contrast, the effects of the supplementation with LCT and DLC on hepatic metabolism were quite similar, ie, both groups showed: (a) intensified ammonia uptake and decreased urea pro duction from ammonia; (b) increased glucose and urea production from L-glutamine (5 mmol/L). CONCLU SION: The results suggested that LCT supplementation might protect against ammonia toxicity by extra-hepatic mechanisms.

  4. The Role of Neonatal Carnitine Palmitoyl Transferase Deficiency Type II on Proliferation of Neuronal Progenitor Cells and Layering of the Cerebral Cortex in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Heepeel Chang

    2007-06-01

    Full Text Available Neonatal Carnitine Palmitoyl Transferase Deficiency Type II, characterized by the absence of CPT II enzyme, is one of the lethal disorders of mitochondrial fatty acid oxidation. CPT II regulates the conversion of long chain fatty acids, so that its product, acyl-CoA esters, can enter the Krebs cycle and generate energy. Neonatal mutations of CPT II lead to severe disruption of the metabolism of long-chain fatty acids and result in dysmorphic features, cystic renal dysplasia, and neuronal migration defects. Examination of the brain from an approximately 15-week gestation human fetus with CPT II deficiency revealed premature formation of cerebral cortical gyri and sulci and significantly lower levels of neuronal cell proliferation in the ventricular and subventricular zones as compared to the reference cases. We used immunohistochemical markers to further characterize the effect of CPT II deficiency on progenitor cell proliferation and layering of neurons. These studies demonstrated a premature generation of layer 5 cortical neurons. In addition, both the total number and percentage of progenitor cells proliferating in the ventricular zone were markedly reduced in the CPT II case in comparison to a reference case. Our results indicate that CPT II deficiency alters the normal program of cellular proliferation and differentiation in the cortex, with early differentiation of progenitor cells associated with premature cortical maturation.

  5. Modulatory effects of vitamin E, acetyl-L-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer's disease in rat model.

    Science.gov (United States)

    Ahmed, Hanaa H

    2012-09-01

    Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder associated with aging. This study aimed to explore new markers for AD as total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); to determine the modulatory effects of vitamin E (VE), acetyl-L-carnitine (ALC) and α-lipoic acid (LA) on the investigated parameters and to evaluate the possible therapeutic role of these nutraceutical in AD-induced in rats. Our results revealed that brain acetylcholine esterase (AChE) activity and tHcy levels were significantly increased in AD model. Folic acid, vitamin B(12) levels and Na(+)/K(+) ATPase activity were markedly reduced. Plasma insulin and IGF-1 levels were noticeably decreased but plasma TNF-α and IL-1β concentrations were significantly increased, confirming that abnormal inflammatory response is associated with AD. Treatment by VE, ALC and LA restored the above mentioned parameters to about normal levels comparable to those of donepezil, indicating that tHcy, insulin, IGF-1, IL-1β and TNF-α may be considered as new biomarkers for AD. The study points to the potential restoring effects of VE, ALC and LA in AD model. Our study provides evidence for the importance of dietary supplementation in delaying the progression of age-related neurodegenerative diseases. PMID:21183322

  6. Molecular characterization of carnitine palmitoyltransferase IA in Megalobrama amblycephala and effects on its expression of feeding status and dietary lipid and berberine.

    Science.gov (United States)

    Lu, Kang-Le; Zhang, Ding-Dong; Wang, Li-Na; Xu, Wei-Na; Liu, Wen-Bin

    2016-01-01

    Carnitine palmitoyltransferase I (CPT I, EC 2.3.1.21) controls the main regulatory step of fatty acid oxidation, and hence studies of its molecular characterization are useful to understand lipid metabolism in cultured fish. Here, a full-length cDNA coding CPT I was cloned from liver of blunt snout bream Megalobrama amblycephala. This cDNA obtained covered 2499bp with an open reading frame of 2181bp encoding 726 amino acids. This CPT I mRNA predominantly expressed in heart and white muscle, while little in eye and spleen. The phylogenetic tree constructed on the basis of sequence alignments among several vertebrate species suggests that this blunt snout bream CPT I sequence belongs to the CPT IA family. In order to investigate the characterization of CPT IA mRNA expression, post-prandial experiment and feeding trial were conducted. The results showed that CPT IA mRNA expression was unchanged from 2 to 12h, and then significantly increased at 24h post-feeding in liver and heart. Berberine, an alkaloid, was identified as a promising lipid-lowering drug. In order to elucidate the effect of berberine on CPT I expression, fish were fed for 8 weeks with three diets (low-fat diet (LFD, 5% fat), high-fat diet (HFD, 15% fat), and berberine-supplemented diet (BSD, 15% fat). The results showed that HFD could decrease the expression of CPT IA and PPARα, while BSD increased those expressions.

  7. Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat.

    Science.gov (United States)

    Farahpour, Mohammad Reza; Ghayour, Sina Jangkhahe

    2014-12-01

    The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P fibers showed number and diameter of the myelinated fibers in CHIT/ALC were significantly higher than in control group. In immuohistochemistry, the location of reactions to S-100 in CHIT/ALC was clearly more positive than CHIT group. ALC when loaded in a chitosan conduit resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve. PMID:25448663

  8. Genetic analysis of ryanodine receptor 1 gene and carnitine palmitoyltransferase II gene: an autopsy case of neuroleptic malignant syndrome related to vegetamin.

    Science.gov (United States)

    Matsusue, Aya; Hara, Kenji; Kageura, Mitsuyoshi; Kashiwagi, Masayuki; Lu, Wang; Ishigami, Akiko; Gotohda, Takako; Tokunaga, Itsuo; Nisimura, Akiyoshi; Sugimura, Tomoko; Kubo, Shin-ichi

    2009-04-01

    We report an autopsy case of a man in his forties who died 2 days after taking an overdose of vegetamin. The autopsy findings were as follows: externally, the upper epidermis of some parts of the body had become loosened. The epidermis was easily detached from the dermis using the fingers. Viscous fluid adhered around the nose and mouth. The brain was edematous and weighed 1520 g. Skeletal muscle was discolored. The urine was a slightly red-tinged yellow. The organs showed congestion. Urine tests: urea nitrogen: 1.95 g/day; creatinine: 0.66 g/day; urine myoglobin: 1100 ng/mL. Blood level of drugs: phenobarbital: 38.2 microg/ml; promethazine: 2.22 microg/ml; chlorpromazine: 0.96 microg/ml. Immunohistochemistry identified myoglobin in the kidney. From these findings, his cause of death was considered to be vegetamin-induced neuroleptic malignant syndrome and rhabdomyolysis. Mutation of the ryanodine receptor 1 gene is associated with malignant hyperthermia. However, there was no mutation which causes amino acid substitution in the three hot-spot regions of the ryanodine receptor 1 gene. Partial deficiency of carnitine palmitoyltransferase II is the commonest cause of recurrent rhabdomyolysis in adults. The subject was found to be heterozygous for an amino acid exchange in exon 4, (1203)G-->A causing a (368)Val-->Ile amino acid substitution. It is necessary to examine other candidate gene mutations. PMID:19269221

  9. Cats in Positive Energy Balance Have Lower Rates of Adipose Gain When Fed Diets Containing 188 versus 121 ppm L-Carnitine

    Science.gov (United States)

    Gooding, M. A.; Minikhiem, D. L.

    2016-01-01

    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 (P 0.05). 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 (P 0.05). 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.

  10. Cats in Positive Energy Balance Have Lower Rates of Adipose Gain When Fed Diets Containing 188 versus 121 ppm L-Carnitine.

    Science.gov (United States)

    Gooding, M A; Minikhiem, D L; Shoveller, A K

    2016-01-01

    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 (P 0.05). 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 (P 0.05). 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. PMID:27652290

  11. Cats in Positive Energy Balance Have Lower Rates of Adipose Gain When Fed Diets Containing 188 versus 121 ppm L-Carnitine

    Science.gov (United States)

    Gooding, M. A.; Minikhiem, D. L.

    2016-01-01

    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 (P 0.05). 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 (P 0.05). 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. PMID:27652290

  12. Molecular and biochemical evidence on the protection of cardiomyocytes from phosphine-induced oxidative stress, mitochondrial dysfunction and apoptosis by acetyl-L-carnitine.

    Science.gov (United States)

    Baghaei, Amir; Solgi, Reza; Jafari, Abbas; Abdolghaffari, Amir Hossein; Golaghaei, Alireza; Asghari, Mohammad Hossein; Baeeri, Maryam; Ostad, Seyed Nasser; Sharifzadeh, Mohammad; Abdollahi, Mohammad

    2016-03-01

    The aim of the present study was to investigate the efficacy of acetyl-L-carnitine (ALCAR) on pathologic changes of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cellular apoptosis/necrosis induced by aluminum phosphide (AlP) poisoning. The study groups included: the Sham that received almond oil only; the AlP that received oral LD50 dose of aluminum; the AC-100, AC-200, and AC-300 which received concurrent oral LD50 dose of AlP and single 100, 200, and 300 mg/kg of ALCAR by intraperitoneal injection. After 24 h, the rats were sacrificed; the heart and blood sample were taken for measurement of biochemical and mitochondrial factors. The results specified that ALCAR significantly attenuated the oxidative stress (elevated ROS and plasma iron levels) caused by AlP poisoning. ALCAR also increased the activity of cytochrome oxidase, which in turn amplified ATP production. Furthermore, flow cytometric assays and caspase activity indicated that ALCAR prohibited AlP-induced apoptosis in cardiomyocytes. PMID:26773361

  13. Different involvement of promoter methylation in the expression of organic cation/carnitine transporter 2 (OCTN2 in cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Qiang Qu

    Full Text Available Organic cation/carnitine transporter 2 (OCTN2 is responsible for the cellular uptake of the antineoplastic agent, oxaliplatin. Epigenetic modification is a possible mechanism of altered drug-transporter expression in cancers, leading to altered efficacy of chemotherapeutic drugs. However, the mechanisms governing OCTN2 regulation are not completely understood. In this study, the low levels of OCTN2 in HepG2 and LS174T cells were elevated by the demethylating reagent, decitabine (DCA. To further reveal the epigenetic mechanism of down-regulation of OCTN2, we found that Region-1 within the OCTN2 promoter (spanning -354 to +85 was a determinant of OCTN2 expression in a luciferase reporter assay. Moreover, methylation-specific PCR (MSP and bisulfite genomic sequencing showed that the degree of individual methylated CpG sites within this region was inversely correlated with the levels of OCTN2 in different cancer cells. Application of DCA to HepG2 and LS174T cells reversed the hypermethylation status of the OCTN2 promoter and increased OCTN2 expression, enhancing cellular uptake of oxaliplatin. Thus, we identified that promoter methylation is responsible for epigenetic down-regulation of OCTN2 in HepG2 and LS174T cells. Given the essential role of OCTN2 in cancer cell uptake of chemotherapeutics, and thus treatment efficacy, pretreatment with a demethylating reagent is a possible strategy for optimizing pharmacotherapies against cancers.

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. A mixture of the aqueous extract of Garcinia cambogia, soy peptide and l-carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet

    OpenAIRE

    Kim, Yun Jung; Kim, Keun-Young; Kim, Min Sun; Lee, Jin Hee; Lee, Kang Pyo; Park, Taesun

    2007-01-01

    The aim of the present study was to investigate the anti-obesity effect of a mixture composed of Garcinia cambogia extract, soypeptide, and l-carnitine (1.2:0.3:0.02, w/w/w) in rats rendered obese by a high-fat diet (HFD). Sprague-Dawley rats were fed either the high-fat control diet (CD) or the 0.38% mixture-supplemented HFD (CD + M) for 9 weeks. The mixture significantly reduced body weight gain and the accumulation of visceral fat mass in a rat model of HFD-induced obesity. Moreover, the m...

  16. Metabolic Agents that Enhance ATP can Improve Cognitive Functioning: A Review of the Evidence for Glucose, Oxygen, Pyruvate, Creatine, and l-Carnitine

    Directory of Open Access Journals (Sweden)

    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.

  17. Muscle expression of a malonyl-CoA-insensitive carnitine palmitoyltransferase-1 protects mice against high-fat/high-sucrose diet-induced insulin resistance.

    Science.gov (United States)

    Vavrova, Eliska; Lenoir, Véronique; Alves-Guerra, Marie-Clotilde; Denis, Raphaël G; Castel, Julien; Esnous, Catherine; Dyck, Jason R B; Luquet, Serge; Metzger, Daniel; Bouillaud, Frédéric; Prip-Buus, Carina

    2016-09-01

    Impaired skeletal muscle mitochondrial fatty acid oxidation (mFAO) has been implicated in the etiology of insulin resistance. Carnitine palmitoyltransferase-1 (CPT1) is a key regulatory enzyme of mFAO whose activity is inhibited by malonyl-CoA, a lipogenic intermediate. Whereas increasing CPT1 activity in vitro has been shown to exert a protective effect against lipid-induced insulin resistance in skeletal muscle cells, only a few studies have addressed this issue in vivo. We thus examined whether a direct modulation of muscle CPT1/malonyl-CoA partnership is detrimental or beneficial for insulin sensitivity in the context of diet-induced obesity. By using a Cre-LoxP recombination approach, we generated mice with skeletal muscle-specific and inducible expression of a mutated CPT1 form (CPT1mt) that is active but insensitive to malonyl-CoA inhibition. When fed control chow, homozygous CPT1mt transgenic (dbTg) mice exhibited decreased CPT1 sensitivity to malonyl-CoA inhibition in isolated muscle mitochondria, which was sufficient to substantially increase ex vivo muscle mFAO capacity and whole body fatty acid utilization in vivo. Moreover, dbTg mice were less prone to high-fat/high-sucrose (HFHS) diet-induced insulin resistance and muscle lipotoxicity despite similar body weight gain, adiposity, and muscle malonyl-CoA content. Interestingly, these CPT1mt-protective effects in dbTg-HFHS mice were associated with preserved muscle insulin signaling, increased muscle glycogen content, and upregulation of key genes involved in muscle glucose metabolism. These beneficial effects of muscle CPT1mt expression suggest that a direct modulation of the malonyl-CoA/CPT1 partnership in skeletal muscle could represent a potential strategy to prevent obesity-induced insulin resistance. PMID:27507552

  18. Upregulation of mGlu2 receptors via NF-κB p65 acetylation is involved in the Proneurogenic and antidepressant effects of acetyl-L-carnitine.

    Science.gov (United States)

    Cuccurazzu, Bruna; Bortolotto, Valeria; Valente, Maria Maddalena; Ubezio, Federica; Koverech, Aleardo; Canonico, Pier Luigi; Grilli, Mariagrazia

    2013-10-01

    Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-κB p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-κB pathway, and in particular by p65 acetylation, and subsequent NF-κB-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressants. PMID:23670591

  19. Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity.

    Science.gov (United States)

    Maples, Jill M; Brault, Jeffrey J; Witczak, Carol A; Park, Sanghee; Hubal, Monica J; Weber, Todd M; Houmard, Joseph A; Shewchuk, Brian M

    2015-08-15

    The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity. PMID:26058865

  20. L-carnitine Effectively Induces hTERT Gene Expression of Human Adipose Tissue-derived Mesenchymal Stem Cells Obtained from the Aged Subjects

    Science.gov (United States)

    Farahzadi, Raheleh; Mesbah-Namin, Seyed Alireza; Zarghami, Nosratollah; Fathi, Ezzatollah

    2016-01-01

    Background and Objectives Human mesenchymal stem cells (hMSCs) are attractive candidates for cell therapy and regenerative medicine due to their multipotency and ready availability, but their application can be complicated by the factors such as age of the donors and senescence-associated growth arrest during culture conditions. The latter most likely reflects the fact that aging of hMSCs is associated with a rise in intracellular reactive oxygen species, loss of telomerase activity, decrease in human telomerase reverse transcriptase (hTERT) expression and finally eroded telomere ends. Over-expression of telomerase in hMSCs leads to telomere elongation and may help to maintain replicative life–span of these cells. The aim of this study was to evaluate of the effect of L-carnitine (LC) as an antioxidant on the telomerase gene expression and telomere length in aged adipose tissue-derived hMSCs. Methods For this purpose, cells were isolated from healthy aged volunteers and their viabilities were assessed by MTT assay. Quantitative gene expression of hTERT and absolute telomere length measurement were also performed by real-time PCR in the absence and presence of different doses of LC (0.1, 0.2 and 0.4 mM). Results The results indicated that LC could significantly increase the hTERT gene expression and telomere length, especially in dose of 0.2 mM of LC and in 48 h treatment for the aged adipose tissue-derived hMSCs samples. Conclusion It seems that LC would be a good candidate to improve the lifespan of the aged adipose tissue-derived hMSCs due to over-expression of telomerase and lengthening of the telomeres. PMID:27426092

  1. capacity (ID 4305, 4684), maintenance of normal blood LDL-cholesterol concentrations (ID 1494, 4684), contribution to normal spermatogenesis (ID 1822), “energy metabolism” (ID 1821), and increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy (ID 1495) pursuant

    DEFF Research Database (Denmark)

    Tetens, Inge

    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...

  2. Establishing a relationship between prolactin and altered fatty acid β-Oxidation via carnitine palmitoyl transferase 1 in breast cancer cells

    International Nuclear Information System (INIS)

    Mammary carcinomas have been associated with a high-fat diet, and the rate of breast cancer in overweight post-menopausal women is up to 50% higher than in their normal-weight counterparts. Epidemiological studies suggest that prolactin (PRL) plays a role in the progression of breast cancer. The current study examined breast cancer as a metabolic disease in the context of altered fatty acid catabolism by examining the effect of PRL on carnitine palmitoyl transferase 1 (CPT1), an enzyme that shuttles long-chain fatty acids into the mitochondrial matrix for β-oxidation. The effect of PRL on the adenosine 5'-monophosphate-activated protein kinase (AMPK) energy sensing pathway was also investigated. MCF-7 and MDA-MB-231 breast cancer cells and 184B5 normal breast epithelial cells treated with 100 ng/ml of PRL for 24 hr were used as in vitro models. Real-time PCR was employed to quantify changes in mRNA levels and Western blotting was carried out to evaluate changes at the protein level. A non-radioactive CPT1 enzyme activity assay was established and siRNA transfections were performed to transiently knock down specific targets in the AMPK pathway. PRL stimulation increased the expression of CPT1A (liver isoform) at the mRNA and protein levels in both breast cancer cell lines, but not in 184B5 cells. In response to PRL, a 20% increase in CPT1 enzyme activity was observed in MDA-MB-231 cells. PRL treatment resulted in increased phosphorylation of the α catalytic subunit of AMPK at Thr172, as well as phosphorylation of acetyl-CoA carboxylase (ACC) at Ser79. A siRNA against liver kinase B1 (LKB1) reversed these effects in breast cancer cells. PRL partially restored CPT1 activity in breast cancer cells in which CPT1A, LKB1, or AMPKα-1 were knocked down. PRL enhances fatty acid β-oxidation by stimulating CPT1 expression and/or activity in MCF-7 and MDA-MB-231 breast cancer cells. These PRL-mediated effects are partially dependent on the LKB1-AMPK pathway, although

  3. Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor α and carnitine palmitoyl acyl-CoA transferase 1A

    Institute of Scientific and Technical Information of China (English)

    Yang Cheng; Sébastien Dharancy; Mathilde Malapel; Pierre Desreumaux

    2005-01-01

    AIM: To elucidate the role of the peroxisome proliferator-activated receptor α (PPARα) and its target gene carnitine palmitoyl acyl-CoA transferase 1A (CPT1A)in the pathogenesis of hepatitis C virus (HCV) infection.METHODS: Liver samples were collected from the patients with chronic HCV infection and controls. HepG2cells were transfected with vector pEF352neo carrying.Two independent clones (clone N3 and N4) stably expressing HCV core protein were analyzed. Total RNA was extracted from cells and liver tissues. PPARα and CPT1A mRNAs were quantified by real-time polymerase chain reaction (PCR) using SYBR Green Master. Total extracted proteins were separated by polyacrylamide gel electrophoresis, and electroblotted. Membranes were incubated with the anti-PPARα antibody, then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for PPARα. Protein bands were revealed by an enhanced chemiluminescence reaction for PPARα. For immunohistochemical staining of PPARα, sections were incubated with the primary goat polyclonal antibody directed against PPARα at room temperature.RESULTS: Real-time PCR indicated that the PPARα level and expression level of CPT1A gene in hepatitis C patients lowered significantly as compared with the controls (1.8±2.8 vs 13±3.4, P = 0.0002; 1.1±1.5 vs 7.4+1, ,P = 0.004). Western blot results showed that the level of PPARα protein in the livers of hepatitis C patients was lower than that in controls (2.3±0.3 vs 3.6±0.2,P = 0.009). The immunohistochemical staining results in chronic hepatitis C patients indicated a decrease in PPARα staining in hepatocytes compared with those in the control livers. The in vitro studies found that in the N3 and N4 colon stably expressing HCV core protein, the PPARα mRNA levels were significantly lower than that in the controls.CONCLUSION: The impaired intrahepatic PPARα expression is associated with the pathogenic mechanism in hepatic injury during chronic HCV infection. HCV infection

  4. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kathryn J Swoboda

    Full Text Available BACKGROUND: Valproic acid (VPA has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA in vitro and in vivo. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

  5. 拮抗线粒体穿梭系统关键分子肉毒碱对肝脂肪代谢的影响%Antagonistic key molecule of mitochondrial carnitine shuttle system on effects of hepatic fat metabolism

    Institute of Scientific and Technical Information of China (English)

    姚敏; 汪晓莺; 王理; 姚登福; 姚登兵

    2014-01-01

    目的:探讨拮抗线粒体穿梭系统关键分子肉毒碱对肝脂肪氧化的影响。方法:野生型C57BJ/6j (wt/wt)鼠腹腔注射0.05%(W/W/d)肉毒碱相似物[3-(2,2,2-trimethyl hydrazinium) propionate dihydrate,THP]拮抗循环肉毒碱,对照鼠以等量生理盐水(0.85%,W/V)注射,2周后以乙醚麻醉处死留取肝组织;油红O染色观察肝组织脂肪积聚,从肝组织提取并以放射法分析长、短链脂酰肉毒碱,游离及总肉毒碱浓度。结果:THP 注射后鼠肝脏质量明显高于对照组(P<0.05),油红O染色证实模型鼠肝组织出现大量脂肪积聚,高于对照鼠的5~6倍;肝组织总、长链和游离肉毒碱比浓度(nmol/g湿重肝组织)显著高于对照组(P<0.05),分别为(392.16±53.08) vs (323.78±51.29)、(78.32±9.51) vs (65.80±7.73)和(252.28±28.21) vs (151.46±37.81),短链脂酰肉毒碱比浓度明显低于对照组(61.56±23.28 vs 106.92±41.16)。结论:肉毒碱是保证脂肪酸进行β-氧化关键分子和代谢的重要因素。%Objectiv e: To explore antagonistic key molecule of mitochondrial carnitine shuttle system on effects of hepatic fatty acid metabolism. Methods: Wild type C57BJ/6j(wt/wt) mice were intraperitoneally injected 0.05% of carnitine analogue [(3-(2,2,2-trimethyl hydrazinium, W/W/d) propionate dehydrate,THP)] to antagonistic carnitine, and the control mice with equal quantity saline (0.85%, W/V), and sacrificed with ether anesthesia after two weeks, and the livers were strained with oil red for observing hepatic fatty accumulation and the levels of different type carnitines including total, free, long, and short-chain were quantitatively analyzed in liver tissues by radiometric method. Results: After the mice injected with THP, the liver weight in the injected group was significantly increased(P<0.05) than that in the control group, with the fatty accu-mulation in hepatocytes. The hepatic specific concentrations(nmol/g wet liver) in the

  6. The Effect and Mechanism of L-Carnitine on Reproductive Performance of Sows%L-肉碱对母猪繁殖性能的影响及其作用机理

    Institute of Scientific and Technical Information of China (English)

    邓秋红; 贾刚; 王康宁

    2011-01-01

    L-carnitine, with the basic biological function of transferring the long-chain fatty acid into the mitochondria, has satisfactory effect on the growth and the improvement in the meat quality. In recent years, it has been found that L-carnitine can improve reproductive performance of pregnant and lactating sows. Most studies show that it can improve the sow's body condition and its breeding potential, promote the growth of litters and increase the birth weight and the weaning weight of piglets. The improvement of the sow' s body condition may be owing to the alteration of the fat and the protein metabolism. The higher birth weight of piglets may be owing to the effects that carnitine influences the insulin-like growth factor-axis in sows and leads to greater placenta, which in turn improves intra-uterine nutrition, and stimulates oxidation of glucose in the fetuses. The higher weaning weight may be due to an improved suckling behavior of piglets and the increased sow' s milk production.%L-肉碱的基本生物学功能在于参与长链脂肪酸在线粒体的转运过程,对于畜禽生长发育及肉质改善具有良好的作用.近年来,发现在妊娠和泌乳母猪日粮中添加L-肉碱还能改善母猪繁殖性能,主要表现为改善母猪自身体况及繁殖能力,促进胎儿的生长发育,增加仔猪的初生重及断奶重.母猪体况的改善可能与L-肉碱改变脂肪、蛋白质代谢有关;仔猪初生重的增加可能与肉碱影响胰岛素样生长因子系统( IGFs)促进胎盘生长,促进胎儿葡萄糖的氧化利用有关;而新生仔猪断奶重的提高则可能与仔猪吮乳习惯的改变和母猪泌乳量的增加有关.

  7. Cellular Uptake of TPS-L-Carnitine Synthesised as Transporter-based Renal Targeting Prodrug%转运体介导的肾靶向雷公藤内酯醇前体药物TPS-L-Carnitine的合成及体外细胞摄取研究

    Institute of Scientific and Technical Information of China (English)

    李里; 朱迪; 孙逊

    2012-01-01

    Objective To synthesize transporter-based renal targeting prodrug TPS-L-Camitine and to determine its cellular uptake in vitro. Methods Triptolide (TP) was conjugated with L-carnitine using succinate as the linker to form TPS-L-Carnitine, which could be specifically recognized by OCTN2, a cationic transporter with high affinity to L-Carnitine and is highly expressed on the apical membrane of renal proximal tubule cells. Cellular uptake assays of the prodrug and its parent drug were performed on HK-2 cells, a human proximal tubule cell line, in different temperature, concentration and in the presence of competitive inhibitors. Results TPS-L-Carnitine was taken up into HK-2 cells in a saturable and temperature- and concentration-dependent manner. The uptake process could be inhibited by the competitive inhibitors. The uptake of TPS-L-Carnitine was significantly higher than that of TP at 37 °C in the same drug concentration. TPS-L-Carnitine was taken through endocytosis mediated by transporter. Conclusion TPS-L-Carnitine provides a good renal targeting property and lays the foundation for further studies in vivo.%目的 研究有机阳离子转运体( OCTN2)介导的肾靶向雷公藤内酯醇(TP)前体药物TP丁二酸酯(TPS)-L-肉毒碱(TPS-L-Carnitine)的合成方法和体外靶向细胞摄取.方法 将TP与丁二酸酐在碱性条件下生成TPS,再与L-肉毒碱成酯得前体药物TPS-L-Carnitine,利用OCTN2对L-肉毒碱的特异性识别和结合,使前药主动靶向到肾近端小管上皮细胞.初步研究不同温度、浓度以及竞争抑制剂存在时人近端小管上皮细胞株HK-2细胞对前药和母体药物的摄取.结果 HK-2细胞对前药的吸收可饱和,具有温度和浓度依赖性,可被竞争抑制剂抑制,37℃相同给药浓度时,细胞对TPS-L-Carnitine的摄取明显多于TP,证实细胞对TPS-L-Carnitine的摄取机制是通过转运体介导的内吞作用.结论 TPS-L-Carnitine具有良好的肾靶向性,为进一步体

  8. 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

    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...... palmitoyltransferase 1B). CONCLUSIONS: 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......OBJECTIVE: 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...

  9. Effect of L-carnitine on nutritional status and anemia in maintenance hemodialysispatients%左卡尼汀对血液透析患者营养状态及贫血的影响

    Institute of Scientific and Technical Information of China (English)

    高志光; 张波; 李彦生

    2015-01-01

    目的:探讨左卡尼汀对血液透析患者营养状态及贫血的影响。方法回顾性分析我院2012年4月至2014年8月收治的60例血液透析患者临床资料,按是否给予左卡尼汀分为观察组和对照组,对照组常规透析、改善贫血等治疗,观察组是在对照组基础上,血液透析后观察组给予1.0 g左卡尼汀静脉注射,治疗3个月后比较两组患者贫血和营养状态。结果经过治疗后观察组患者Hb、Alb和Hct水平均较对照组高,差异有统计学意义(P<0.05)。治疗前两组患者TC、TG和BUN水平比较差异均无统计学意义(P>0.05),经过治疗后观察组BUN明显增高,TG明显降低,与对照组比较差异有统计学意义(P<0.05)。两组患者不良反应发生率比较差异无统计学意义(χ2=1.418,P>0.05)。结论左卡尼汀可有效改善血液透析患者的贫血及营养状态,应在血液透析的临床应用中广泛采用。%Objective This paper was to evaluate the application effect of L-carnitine on nutritional status and anemia inmaintenance hemodialysis patients.Methods A retrospective analysis was made on 60 cases of maintenance hemodialysispatients who received treatment in our hospital during April 2012and August 2014, they were divided into experimental group and control group according to whethergiven l-carnitine.Patients in control group were treated with same volume of salineand patients in the experimental group were treated with l-carnitine,nutritional status and anemia of the two groups after the treatment for 3 monthswere compared.Results After the treatment,the levels of Hb,Hct and Alb of experimental group were higher than that of control group, differences were statistically significant ( P 0.05 ).The concentration of BUN of experimental group increasedand TG concentration decreased after the treatment,there were statistically significantdifferences between the two groups (P0

  10. 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.

    2010-01-01

    OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS NADH- and FADH2-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). CONCLUSIONS 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. PMID:20682693

  11. Effect of L-carnitine on energy metabolism during renal ischemic reperfusion injury in rats%左卡尼汀对大鼠肾缺血再灌注损伤时能量代谢的影响

    Institute of Scientific and Technical Information of China (English)

    许益笑; 王德选; 卢立肖; 杨宇真; 杨青; 王丽; 熊锡山

    2011-01-01

    Objective:To probe the effect of L-carnitine on energy metabolism during renal ischemic reperfusion injury and the possible mechanisms.Methods: Model of renal ischemia-reperfusion was established, and 48 SD healthy rats were divided into untreated control and L-carnitine treated groups.Within each group, rats were further divided into four subgroups, Sham, and 1 h, 6 h and 12 h IR group (n=6).The levels of blood serum urea nitrogen (Bun) and creatinine (Scr), the free fatty acid (FFA) content and Na+-K+-ATPase activity in nephritic tissues were measured.The ultrastructural changes in renal tissue were observed under electron microscope.Results: In control groups, compared with those of the sham operation group,Scr and Bun levels at IR6h and IRl2h groups increased significantly (P<0.05 or P<0.01); the FFA content in nephritic tissues at IR12h group went up markedly (P<0.01) while the Na+-K+-ATPase activity of IR6h and IR12h groups declined obviously (P <0.05 or P<0.01).As to the L-carnitine treatment groups,compared with those of the control group rats with the same reperfusion time,the Bun levels of 12 h group and the Scr level of IR6h, 12h groups were obviously lower (each P<0.01); the FFA content in nephritic tissues at IR12h group was markedly lower while the Na+-K+-ATPase activity was obviously higher (each P<0.01).In addition,ultrastructure indicated injuries of the mitochondriarenal in tubular epithelial cell were attenuated after L-carnitine administration.Conclusion: L-carnitine protects kidney against acute renal ischemia reperfusion injury through promotion of β- oxidation of fatty acids, increasing Na+-K+ ATPase activity, and finally grading-up energy metabolism.%目的:探讨左卡尼汀对肾缺血再灌注损伤(RIRI)时能量代谢的影响及其机制.方法:健康SD大鼠48只,随机分为对照组和左卡尼汀治疗组(治疗组),组内再分为假手术组及再灌注1h(IR1h)、6h(IR6h)、12h(IR12h)组(n=6).建立大鼠肾急性

  12. 维持性血透患者应用左卡尼汀治疗的临床分析%The Clinical Analysis of L - Carnitine on Maintenance Hemodialysis Patient

    Institute of Scientific and Technical Information of China (English)

    钱春梅; 王秦; 许涛; 盛晓华; 汪年松

    2014-01-01

    Objective:To observe the clinical effects of combined therapy with Human erythropoietin(EPO)、iron sucrose and L - Carnitine in Maintenance hemodialysis(MHD)patients. To research the improvement of inflammation by L - Carnitine in di-abetes mellitus patients undergoing MHD. Methods:One hundred and sixty - six MHD patients were randomly divided into three groups(A、B、C). Every patients were treated by EPO,group B were treated by EPO and iron sucrose,group C were treated by EPO、iron sucrose and L - Carnitine. All the patients were treated for one year. Hemoglobin(Hb),hematokrit(HCT),Creactive protein (CRP),Triglyceride,cholesterol,total protein and albumin were examined before and after the treatment. According to the protopa-thy,the group C were divided into diabetes mellitus group(n = 18)and non diabetes mellitus group(n = 40). Observe the difference in CRP、white blood cell and neutrophile granulocyte between two groups treated with L - Carnitine. Results:The Hb level of all the three groups were higher than before. Compared with group A and group B,the HB level of group C showed much better. There was significant difference in HB level between group C and another two groups(P < 0. 05). There was significant difference in CRP be-tween group C and group A(P < 0. 05). In group C,diabetes nephropathy group showed significantly lower level of CRP(P < 0. 05). Conclusion:The combined therapy with L - Carnitine,EPO and iron sucrose was better than the treatment of EPO and iron solely. It could effectively control micro - inflammation on diabetes nephropathy and improve the quality of life.%目的:观察重组人红细胞生成素联合蔗糖铁、左卡尼汀治疗维持性血液透析(MHD)患者的临床疗效,研究左卡尼汀对糖尿病肾病 MHD 患者炎症改善情况。方法:166例维持性血液透析患者随机分为 A、B、C 三组,其中 A 组单纯应用益比奥,B 组益比奥联合应用蔗糖铁,C 组益比奥联合应用蔗糖

  13. Neuroprotective effect of L-carnitine on ischemic brain injury in rats%左旋肉碱对大鼠缺血性脑损伤的神经保护作用

    Institute of Scientific and Technical Information of China (English)

    张忠霞; 许顺江; 张宏; 崔冬生; 王涛; 牛静亚; 张睿; 周洁; 裴运海; 李江静

    2012-01-01

    Objective To observe the protective effect of L-carnitine on ischemic brain injury in rats and oxygen-glucose deprivation (OGD) induced damage in PCl2 cells, and to explore its possible mechanisms. Methods The focal cerebral ischemia rat models were made by the suture method. The infarction size was assessed by TTC staining. In vitro, PC12 cells were treated with sodium hydrosulfite (Na2S2O4) in combination with glucose deprivation. Cell viability was analyzed by using MTT assay while the necrosis and apoptosis were observed with SYTOX, PI, TUNEL staining. In addition, the activities of ATPase and SOD, as well as the MDA content, were also detected. Results The infarction size in the LC group was not obviously reduced compared with that of the model group by using TTC staining (P > 0.05). In vitro, when we pretreated PC 12 cells with LC, the cell viability, the activities of SOD and ATPase increased , while the number of apoptotic and necrotic cells, as well as the content of MDA decreased, compared with those of the OGD group (P <0. 05). Conclusion Short-term acute L-carnitine injection has no significant protective effect on ischemic brain injury in rats, but it could protect PC12 cells against oxygenglucose deprivation from damage, and it may exerte these effects through improving cell antioxidant capacity, inhibiting the lipid peroxidation, cell apoptosis and necrosis.%目的 观察左旋肉碱(L-carnitine,LC)对大鼠早期缺血性脑损伤和低氧低糖诱导神经细胞损伤的保护作用,并探讨其可能的作用机制.方法 线栓法制备大鼠局灶性脑缺血模型.TTC染色法观察脑梗死面积的改变.采用连二亚硫酸钠(Na2S2O4)合并低糖培养基培养PC12细胞,建立体外细胞低氧低糖模型;MTT法检测细胞活力的改变;SYTOX、PI、TUNEL染色观察细胞的坏死与凋亡;检测各组细胞SOD、ATP酶活性和MDA含量.结果 LC预处理组大鼠脑梗死灶面积较模型组无明显减小(P>0.05).LC预处理可

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. 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

  16. Localization and Function of Carnitine/Organic Cation Transporter OCTN1/2 in Ocular Epithelium%肉碱/有机阳离子转运体OCTN1/2在眼表上皮细胞的定位及功能

    Institute of Scientific and Technical Information of China (English)

    安翠平; 毕建成; 李宝全; 许顺江; 宋国威

    2014-01-01

    Objective To investigate the localization and transport function of carnitine/organic cation transporter 1/2(OC‐TN1/2) in ocular epithelium ,and to provide a structural and functional basis for further study of transport mechanism of L‐carnitine in human ocular epithelium.Methods Immunofluorescence staining was performed to investigate the localization of OCTN1 or OCTN2 in human ocular epithelial cells or rabbit corneal and conjunctival epithelium.Apical or basal uptake of [3 H]‐L‐carnitine was determined by using the polarized epithelial cells grown onto collagen‐coated porous filter support.Results OCTN1 and OCTN2 proteins were detected in HCLE and HCjE cells ,rabbit corneal and conjunctival epithelium ,and they were predominately located in the membranes of the cells. HCLE and HCjE cells were able to transfer [3 H]‐L‐carnitine and most L‐carnitine was uptaken through the apical part of the cells.Conclusion OCTN1 and OCTN2 are mainly located in the apical part of human corneal and conjunctival epithelial cells ,and they are potentially involved in the transport of L‐carnitine in ocular tis‐sues.%目的:检测肉碱/有机阳离子转运体1/2(carnitine/organic cation transporter 1/2,OCTN1/2)在眼表上皮细胞的表达定位及转运功能,为进一步阐明左旋肉碱在人眼表上皮细胞的转运机制提供实验依据。方法采用免疫细胞化学的方法分别检测人角膜缘上皮(human corneal limbal epithelia ,HCLE)细胞和人结膜上皮(human conjunctival epithe‐lia ,HCjE)细胞以及兔眼角膜和结膜上皮组织中OCTN1和OCTN2的表达定位;利用Ⅰ型胶原蛋白包被的双层培养板培养HCLE和 HCjE细胞,并使之建立紧密连结,采用放射摄入实验检测其基底端和顶端转运[3 H]‐L‐carnitine的功能。结果 OCTN1和OCTN2蛋白在HCLE和HCjE细胞及兔眼角膜和结膜上皮组织中均有表达,且主要分布在细胞膜上;

  17. 左旋卡尼汀在犬心房急性电重构中的抗氧化作用%Anti-oxidative stress effects of L-carnitine on acute atrial electrical re-modeling in dogs

    Institute of Scientific and Technical Information of China (English)

    官媛; 单兆亮; 郑强荪; 张晔; 郭红阳; 王玉堂

    2011-01-01

    目的:探讨左旋卡尼汀(L-carnitine,L-CN)抑制犬心房颤动(房颤)时心房急性电重构的作用机制.方法:18条成年杂种犬,随机分为生理盐水(NS)组、L-CN组和正常对照(normal control,NC)组.NS组予右心房600次/min快速起搏,诱发并维持房颤2 h;起搏前半小时静推生理盐水(300 mg/kg),继以液速50 ml/h维持静脉点滴2 h.L-CN组:右心房600 次/min快速起搏,诱发并维持房颤2 h,起搏前半小时静推L-CN(300 ms/kg),继以2.5mg/(kg·min)(液速50 ml/h)维持静脉点滴2 h.在不同观察时间点测定房颤前后电生理指标及静脉血氧化及抗氧化指标的变化.结果:①房颤后Ns组心房有效不应期(AERP)显著缩短(P<0.01),AERP的频率适应性显著下降(P<0.01);L-cN组房颤前后AERP和频率适应性无显著缩短;L-CN组较Ns组房颤诱发率明显降低(P<0.05).②NS组房颤时静脉血氧化应激产物较NC组显著增多(P<0.05),抗氧化指标显著下降(P<0.01).③L-CN组丙二醛(Malondialdehyd,MDA)生成显著减少(P<0.01),超氧化物歧化酶(superoxide dismutase,SOD)显著增加(P<0.05).结论:L-CN对房颤时氧化应激及电重构有明显保护作用,这种保护机制可能通过清除自由基,抑制脂质过氧化而发挥作用.%AIM: To evaluate the anti-oxidative stress effects of L-carnitine (L-CN) on tachycardiainduced acute atrial electrical remodeling in dogs. METHODS: Eighteen dogs were randomly divided into three groups: normal saline (NS) group, L-CN group and normal control (NC) group. In both NS and L-CN groups, right atrium was paced at 600 beats per minute (bpm) to induce atrial fibrillation (AF) and maintained for 2 h; 0. 9% normal saline (300 mg/kg, IV) or L-carnitine (300 mg/kg, IV)was given before the pace and 0.9% normal saline or L-carnitine [2.5 mg/(kg ·min), 50 ml/h, ID]was administered for 2 h. The observed atrial electrophysiology indexes included atrial effective refractory period (AERP), index of the AERP rate adaptation

  18. 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.

    Science.gov (United States)

    Naclerio, Fernando; Larumbe-Zabala, Eneko; Cooper, Robert; Allgrove, Judith; Earnest, Conrad P

    2015-01-01

    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 (Pexercise 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 (Pexercise leukocytosis. PMID:25915424

  19. 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

    Science.gov (United States)

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    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. PMID:24905907

  20. Effect of diet supplementation with l-carnitine on hepatic catabolism of l-alanine in rats%食物中添加l-卡尼汀对大鼠肝代谢l-丙氨酸的作用

    Institute of Scientific and Technical Information of China (English)

    Vilma A F G GAZOLA; Gisele LOPES; Daniel M LIMEIRA; Ricardo GALLETTO; Sebastiao GAZOLA; Rui CURI; Roberto B BAZOTTE

    2002-01-01

    AIM: To investigate the effects of chronic supplementation with l-carnitine (LCT) on hepatic catabolism ofl-alanine. METHODS: Two groups of male adultWistar rats were used: 1 ) supplemented with LCT ( 1.2mmol@ kg- 1@ d- 1 ) dissolved in the drinking water (LCTgroup) and 2) control group (COG) without LCT supplementation. After one week of LCT supplementationlivers from 24 h-fasted rats were perfused in situ and theproduction of glucose, urea, pyruvate, and l-lactate froml-alanine (5 mmoL/L) were measured. RESULTS:LCT decreased the production of glucose and urea froml-alanine. In agreement, pyruvate and l-lactate production from l-alanine were decreased. However, thesupplementation with LCT did not show any significanteffect on hepatic glucose production from pyruvate (5mmol/L) and l-lactate ( 2 mmol/L). CONCLU-SION: LCT supplementation decreased the conversion ofl-alanine to pyruvate. However the ability of the liver toconvert pyruvate to glucose was not affected by LCTtreatment.

  1. 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.

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

    Science.gov (United States)

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    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. PMID:24905907

  3. 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.

  4. 重症患者血清肉毒碱缺乏相关因素及其对住院时间的影响%Related factor of serum carnitine deficiency and influence of its deficiency on the length of hospital stay in critical ill patients

    Institute of Scientific and Technical Information of China (English)

    周昭雄; 邱春芳; 陈传希; 王陆豪; 陈娟; 陈敏英; 管向东; 欧阳彬

    2014-01-01

    )血清肉毒碱浓度较≤7 d者(3例)略有降低(μmol/L:8.44±5.00比13.24±3.65, t=1.610,P=0.119);血清肉毒碱浓度与ICU住院时间无相关性(r=-0.019,P=0.293)。住院病死率26.67%(8/30),死亡组与存活组血清肉毒碱无差异(μmol/L:12.24±6.52比7.72±3.91,t=-1.846,P=0.098);且血清肉毒碱浓度与住院病死率无相关性(r=0.340,P=0.066)。结论重症患者血清肉毒碱浓度明显下降,血清肉毒碱浓度与病情严重程度、血清TBil浓度相关;血清肉毒碱浓度较低的患者肠内喂养总量减少,住院时间延长。%Objective To investigate the related factors of serum carnitine deficiency in critical ill patients, and the influence of its deficiency on the length of hospital stay. Methods A prospective study was conducted. Critical ill patients with acute physiology and chronic health evaluationⅡ(APACHEⅡ)score>12 admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Sun Yat-sen University from March 2013 to September 2013 were enrolled. Serum carnitine concentration and indexes of organ function were determined,and the tolerance of enteral nutrition within 5 days,the length of hospital stay,the length of intensive care unit(ICU)stay,and the hospital mortality were recorded. The relationship between serum carnitine and indexes mentioned above was analyzed. Results Thirty critically ill patients were enrolled. Serum carnitine concentration was very low in all critically ill patients,i.e. (8.92±5.05)μmol/L(normal reference value at 43.5 μmol/L)at hospital admission. Serum carnitine concentration in patients with APACHEⅡscore>23(7 cases)was significantly lower than that in those with APACHEⅡscore 12-23(23 cases,μmol/L:5.33±1.72 vs. 10.02±5.24,t=2.300,P=0.001). Serum carnitine concentration in patients with serum total bilirubin(TBil)>19μmol/L(9 cases)was significantly lower than that in those with

  5. Ectoine and hydroxyectoine as protectants against osmotic and cold stress: uptake through the SigB-controlled betaine-choline- carnitine transporter-type carrier EctT from Virgibacillus pantothenticus.

    Science.gov (United States)

    Kuhlmann, Anne U; Hoffmann, Tamara; Bursy, Jan; Jebbar, Mohamed; Bremer, Erhard

    2011-09-01

    Virgibacillus pantothenticus has been shown to synthesize the compatible solute ectoine in response to high salinity or low growth temperature. We found that exogenously provided ectoine and hydroxyectoine also serve as protectants against these challenges. Transport studies with [(14)C]ectoine revealed that both types of stress induced a high-affinity ectoine uptake activity in V. pantothenticus. By using an Escherichia coli mutant defective in osmoprotectant uptake systems, a functional complementation approach for osmostress resistance in the presence of ectoine was employed to retrieve a gene encoding an ectoine transporter from V. pantothenticus. The cloned gene (ectT) encodes a protein (EctT) that is a member of the BCCT (betaine-choline-carnitine-transporter) family of carriers. Osmoprotection assays demonstrated that the EctT carrier mediates the preferential import of ectoine and hydroxyectoine but also possesses minor uptake activities for the compatible solutes proline and glycine betaine. Northern blot analysis with RNA isolated from V. pantothenticus revealed that a rise in the external osmolality or a reduction in growth temperature strongly increased the transcription of the ectT gene. Primer extension analysis demonstrated that ectT was transcribed under these conditions from a SigB-type promoter. SigB is the master regulator of the general stress regulon of bacilli and provides protection to cells against various challenges, including high salinity and low temperature. Both the synthesis of ectoine and the EctT-mediated uptake of ectoine and hydroxyectoine are triggered by the same environmental cues, high salinity and cold stress, and thereby provide, in a concerted fashion, the protection of V. pantothenticus against these challenges. PMID:21764932

  6. 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 < 0.05, One-way ANOVA and Newman-Keuls test). CO increased levels of ALA and EPA compared to RMO (p < 0.05). No significant differences were observed for DHA levels. CO also increased the expression of PPAR-α, ACOX1 and CAT-I. Only CAT-I levels were increased by RO. CO and RMO may be a nutritional alternative to provide ALA for its bioconversion to EPA and DHA, and to increase the expression of PPAR-α, ACOX1 and CAT-I, especially CO-oil.

  7. Protective effects of L-carnitine upon testicular ischemia-reperfusion damage in rats%左旋卡尼汀对大鼠睾丸缺血再灌注损伤的防护作用

    Institute of Scientific and Technical Information of China (English)

    官毅; 郑新民; 杨志伟; 李世文

    2009-01-01

    目的 探讨左旋卡尼汀对大鼠睾丸缺血再灌注后生精功能的影响.方法 30只成年健康雄性SD大鼠随机分为对照组、扭转组和治疗组,每组10只,建立右侧睾丸扭转复位动物模型(720°,2 h).扭转组和治疗组于复位前30 min分别腹腔注射生理盐水和左旋卡尼汀(500 mg/kg).复位后4 +h,每组各处死5只取扭转侧睾丸,分别检测组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)、过氧化氖酶(CAT)、谷胱甘肽过氧化物酶(GPx)活性以及热休克蛋白70(HSP70)的含量.复位后24 h,取每组剩余大鼠的扭转侧睾丸,检测生精细胞凋亡指数(AI)和组织病理学参数.结果 治疗组平均生精细胞AJ和MDA水平明显低于扭转组[AJ(6.87 4±2.47)比(17.13 4±3.56),MDA(160±15)比(199 ±15)nmoL/g],抗氧化酶活性和HSP70含量显著高于扭转组[SOD(1638±153)比(1078 4±158)U/g,CAT(317±28)比(188 ±33)U/g,GPx(667 ±94)比(311±65)U/g,HSP70(0.87±0.13)比(0.25 ±0.04)],组织病理学损害较扭转组轻,差异均有统计学意义(均P<0.05).结论 左旋卡尼汀对睾丸缺血再灌注后的生精能力具有保护作用,其机制可能是通过诱导热休克蛋白表达而实现.%Objective To investigate the protective effects of L-carnitine upon testicular ischemiareperfusion injury in rats. Methods Sprague-Dawley rats were divided into 3 groups (n = 10). In those animals undergoing unilateral testicular torsion, right testes were rotated 720° for 2 h. Sham operated group served as a control group. Torsion group underwent 2 h torsion and saline was injected intraperitoneally at 30min pre-detorsion. Treatment group underwent similar torsion but L-carnitine (500 mg/kg) was infused intraoperatively. The right testes of 5 animals in each group were excised after 4 h reperfusion for measuring the levels of malondialdehyde (MDA) and heat shock protein 70 (HSPT0), evaluation of activities of antioxidant enzyme including superoxide dismutase (SOD), catalase (CAT

  8. Effects of Dietary L-Carnitine on Growth Performance, Body Composition and Blood Parameters of Japanese Flounder (Paralichthys olivaceus) Juvenile%饲料中添加L-肉碱对牙鲆幼鱼生长、生化组成及血液指标的影响

    Institute of Scientific and Technical Information of China (English)

    高小强; 田青杰; 石洪玥; 姜志强

    2012-01-01

    The effects of L-carnitine on growth performance, body composition and blood parameters for juvenile Japanese flounder {Paralichthys olivaceus) with initial body weight of 10.30 ?0.12 g were investigated. The juveniles were fed with diets that supplied with Z-carnitine at 0, 300, 600, 900, 1 200 and 1 500 mg/kg diet. The results showed that juveniles fed with the diet added with 1 200 mg/kg I-carnitine got significant rise in body weight and special growth rate in contrast to that in control group, and the feed conversion ratio in this group got significantly lower than that in control group (P0.05). Crude lipid of muscle and liver were negative correlation with supplemented with Z-carnitine, and there were significant differences compared with the control group (P 0.05). Glutamate-oxaloacetate transaminase (AST), total cholesterol (CHOL), triglyceride (TG) and blood urea nitrogen (BUN) that supplemented with 1 200 mg/kg L-carnitine were significantly lower than that of the control group (P0.05), but the content of total protein and low density lipoprotein was descended and the content of high density lipoprotein was promoted, according to the increased dietary I-carnitine level. In conclusion, under the condition of this experiment, adding I-carnitine will promote the growth parameters of Japanese Flounde (Paralichthys olivaceus) and reduce crude lipid content of fish, at the same time, the optimal dietary L-carnitine level was estimated to be 1200 mg/kg.%研究0、300、600、900、1 200、1 500 mg/kg 6个L-肉碱添加水平对牙鲆(Paralichthys olivaceus)幼鱼生长、生化组成和血液指标的影响.结果表明:添加量为1 200 mg/kg的处理组牙鲆幼鱼的增重率和特定生长率显著提高,饲料系数显著降低(P< 0.05);随着饲料中L-肉碱含量的增加,肝指数呈现下降趋势,且在添加量为900~1 500 mg/kg时,各组较对照组差异显著(P<0.05);饲料中添加L-肉碱显著降低各实验组脏体比(P<0.05),而

  9. 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.

    Directory of Open Access Journals (Sweden)

    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.

  10. 添加不同植物油和L-肉碱对公猪精液品质和性欲的影响%Different Vegetable Oils and L-carnitine Influence Libido and Semen Characteristics of Breeding Boars

    Institute of Scientific and Technical Information of China (English)

    白小龙; 吴德; 林燕; 方正锋; 车炼强; 单妹

    2011-01-01

    The study was conducted to investigate the effects of supplementation with polyunsaturated fatty acids of different vegetable oils and L-carnitine on boar libido, semen characteristics, fatty acid composition of sperm and semen antioxidant properties. Thirty adult Pietrain x Duroc hybrid boars with similar age and body condition were randomly divided into 3 groups with 10 replicates and 1 pig in each replicate. The diet of group 1 was supplemented with 1.5% soybean oil; group 2 was supplemented with 1.5% soybean oil +200 mg/kg L-carnitine; group 3 was supplemented with 0. 3% of soybean oil +1.2% flax seed oil +200 mg/kg L-carni-tine. The feeding trial lasted for 16 weeks. The results showed that the semen volume and ejaculation duration of boars in group 3 were significantly higher than those in the other two groups (P 0.05). During 8 to 16 weeks, the sperm docosahexaenoic acid (DHA, n-3) content and activity of superoxide dismutase (SOD) of boars in group 3 were significantly higher than those in the other groups (P <0.05). The malondialdehyde ( MDA) content in semen of boars in group 1 was significantly higher than those in the other groups (P <0.01) during 8 to 16 weeks. The results suggest that dietary polyunsaturated fatty acids and L-camitine could enhance the boar libido, increase the sperm DHA content and semen antioxidant properties, and finally improve the boar semen production, sperm motility and sperm density. [Chinese Journal of Animal Nutrition, 2011, 23(8):1361-1369]%本研究旨在考察富含多不饱和脂肪酸(polyunsaturated fatty acid,PUFA)的不同植物油和L-肉碱的不同添加方式对种公猪精液品质、性欲、精子脂肪酸组成及精液抗氧化性能的影响.试验选用30头年龄、体况相近的成年皮特兰×杜洛克杂交种公猪,随机分为3组,每组设10个重复,每个重复1头猪.试验组公猪分别饲喂添加1.5%大豆油(试验组1)、1.5%大豆油+ 200 mg/kg L-肉碱(试验组2)、0.3%大豆油+1.2%

  11. Effects of L-carnitine on the contents of MPO and NO in rats with renal ischemic reperfusion injury%左卡尼汀对肾缺血再灌注损伤大鼠肾组织MPO和NO含量的影响

    Institute of Scientific and Technical Information of China (English)

    许益笑; 张睿喆; 王德选; 倪世容; 王万铁; 郑绿珍; 王丽; 熊锡山; 郭坤元

    2012-01-01

    Aim:To investigate possible mechanisms involved in the protection of L-carnitine against renal ischemic reperfusion injury( RIRI ) in rats. Methods:A total of 48 SD healthy rats were divided into control and L-carnitine groups ( n = 24 ). Model of RIRI was established in the two groups,and 6 rats were killed at ischemic reperfusion( IR ) 0,1 ,6,and 12 h. The contents of serum urea nitrogen( BUN ) and creatinine( Cr ),the myeloperoxidase ( MPO ) and NO in nephridial tissue were measured. The pathological changes in renal tissue were observed. Results:In the two groups,Cr and BUN contents of the IR 0 ,1,6,12 h rats were obviously different F_group = 5. 116 and 6. 602, F_time = 15. 235 and 47. 118 ,P < 0. 05 ). Comparing with those of IR 0 h killed rats ,Cr and BUN contents of the IR 6 and 12 h killed rats increased significantly; Cr and BUN contents of the IR 6 and 12 h killed rats were lower in L-carnitine group than those in the control group( P < 0. 05 ). In the two groups, MPO and NO contents of the IR 0,1,6,12 h rats were obviously different( F_group = 6. 259 and 3.729,F_time =7.709 and 39.671 ,P <0.05 ). Comparing with those of IR 0 h killed rats,MPO content of the IR 12 h killed rats increased significantly in the two groups;MPO content of the IR 12 h killed rats was higher in control group than that in the L-carnitine group( P <0.05 ). In the two groups,comparing with those of IR 0 h killed rats,NO content of the IR 12 h killed rats decreased significantly; NO content of the IR 12 h killed rats was lower in control group than that in the L-carnitine group( P <0.05 ). In addition,renal histological injuries were attenuated after L-carnitine administration. Conclusion: L-carnitine protects kidney against acute RIRI through inhibiting neutrophil aggregation,lowering the release of MPO and increasing the synthesis of NO in the renal tissue.%目的:探讨左卡尼汀对肾缺血再灌注损伤(RIRI)大鼠能量代谢的影响及其机制.方法:健康SD大鼠48只

  12. 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

  13. Genetics Home Reference: carnitine palmitoyltransferase II deficiency

    Science.gov (United States)

    ... myalgia and rhabdomyolysis may be triggered by exercise, stress, exposure to extreme temperatures, infections, or fasting. The first episode usually occurs during childhood or adolescence. Most people with the myopathic form of CPT ...

  14. 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

  15. Effects of exogenous carnitine on function of respiratory chain and antioxidant capacity in mitochondria of myocardium after exhaustive running in rats%肉碱对大鼠力竭运动后心肌线粒体呼吸链功能及抗氧化能力的影响

    Institute of Scientific and Technical Information of China (English)

    李洁; 余小燕

    2012-01-01

    目的:探讨肉碱对大鼠心肌线粒体呼吸链功能及抗氧化能力的影响.方法:40只2月龄雄性Wistar大鼠随机均分为4组(n=10):对照组(C)、补充肉碱组(LC)、运动训练组(T)、运动训练+补充肉碱组(TLC).LC和TLC组每天按300 mg/(kg bw.d)剂量灌胃补充肉碱一次,T组和TLC组进行递增负荷水平跑台运动训练,共6周.力竭运动后即刻取样,差速离心法提取线粒体.分光光度法测定线粒体呼吸链CⅠ~Ⅳ、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量.结果:与C组相比,LC组、T组和TLC组CⅠ及CⅣ活性均显著升高(P<0.05,P<0.01),T组和TLC组CⅡ及CⅢ活性均显著升高(P<0.05,P<0.01);与LC组相比,TLC组CⅠ~Ⅳ活性均显著升高(P<0.05,P<0.01);与T组相比,TLC组CⅠ及CⅣ活性均显著升高(P<0.05).与C组相比,LC组、T组和TLC组SOD活性均显著升高、MDA含量均显著降低(P <0.05,P<0.01);与LC组和T组相比,TLC组SOD活性均显著升高、MDA含量均显著降低(P<0.05).结论:补充肉碱及运动训练均可提高心肌线粒体呼吸链功能及抗氧化能力,从而提高机体的运动能力,且肉碱与运动训练具有协同作用.%Objective: To investigate the effect of exogenous carnitine on function of respiratory chain and antioxidant capacity in mitochondria of myocardium in rats. Methods: Forty male Wistar rats were randomized to 4 groups ( n = 10): static control(C) , supplementation of carnitine(LC) , exercise-training(T) and training with supplementation of carnition(TLC) . LC and TLC animals were perfused carnitine by the dose of 300 nig/kg bwd. T and TLC animals were forced to performed 6-week treadmill training. Heart were prepared immediately after exhaustive running. Myocardium mitochondria was extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complex (C) I -IV and superoxide dismutase (SOD) , malondialdehyde (MDA) level

  16. Effects of Dietary L-carnitine on Performance, Egg Quality and Lipid Metabolism in Laying Hens%饲粮中添加L-肉碱对产蛋鸡生产性能、蛋品质及脂质代谢的影响

    Institute of Scientific and Technical Information of China (English)

    徐少辉; 武书庚; 张海军; 齐广海

    2011-01-01

    本试验旨在研究饲粮中添加L-肉碱对产蛋鸡生产性能、蛋品质和脂质代谢的影响.选用576只产蛋率和体重相近、健康的53周龄海兰褐产蛋鸡,随机分成6个处理,每个处理6个重复,每个重复16只鸡.6种试验饲粮分别添加0、25、50、100、200或400 mg/kg L-肉碱,试验期6周.结果表明:1)饲粮中添加L-肉碱未显著影响产蛋率、日采食量、平均蛋重和料蛋比(P>0.05);2)饲粮中添加L-肉碱显著提高了试验第3周时鸡蛋的蛋白高度和哈夫单位(P<0.05),其中以25 mg/kg组最佳;添加L-肉碱还提高了试验第6周时鸡蛋蛋壳强度(P<0.05),其中25 mg/kg组和200 mg/kg组较佳;饲粮中添加L-肉碱有提高试验第3周和第6周蛋黄颜色的趋势(P=0.07,P=0.06),对蛋壳厚度和蛋形指数影响不显著(P>0.05);3)饲粮中添加L-肉碱显著降低了产蛋鸡血清中甘油三酯和低密度脂蛋白胆固醇含量及试验第6周总胆固醇和高密度脂蛋白胆固醇含量(P<0.05).由此可知,饲粮添加L-肉碱不影响产蛋鸡生产性能,但可改善鸡蛋品质,降低血脂;综合考虑成本和鸡蛋品质,以饲粮中添加L-肉碱25 mg/kg为宜.%The objective of this study was to investigate the effects of dietary L-camitine on performance, eggquality and lipid metabolism in laying hens. A total of five hundred and seventy-six 53-week-old healthy Hyline laying hens with similar egg production rate and body weight were chosen and divided into 6 groups with 6 replicates per group and 16 hens per replicate. The diets were the corn-soybean meal based diets with different levels of L-carnitine (0, 25, 50, 100, 200 and 400 mg/kg). The experiment lasted for 6 weeks. The results showed as follows: 1 ) L-camitine supplementation had no significant effects on egg production rate, average egg weight, daily feed intake, and ratio of feed to egg weight ( P > 0.05 ); 2 ) the supplementation of L-cami-tine in the diet significantly increased the

  17. 蝇蛆粉和L-肉碱对青鱼生长、免疫与抗氧化指标及抗病力的影响%The Influence of Maggot Meal and L-Carnitine on Growth,Immunity, Antioxidant Indices and Disease Resistance of Black Carp(Mylopharyngodon Piceus)

    Institute of Scientific and Technical Information of China (English)

    明建华; 叶金云; 张易祥; 杨霞; 吴成龙; 邵仙萍; 刘沛

    2013-01-01

    This experiment was conducted to study the influences of dietary maggot meal and L - carnitine on growth, non - specific immunity and antioxidant capacity of black carp (Mylopharyngodon piceus ). 270 healthy fish with initial body weight of (72. 23 ± 1. 81) g were selected and randomly divided into three groups;one control and two tested. Three isonitrogenous and isoenergetic diets were formulated, when the control group was fed with basal diet and two tested groups were fed with diets supplemented with 25 g/kg maggot meal and 150 mg/kg L - carnitine respectively. After feeding them for 60 days, we investigated the growth performance, muscle composition, biochemical parameters of blood and liver and mortality and relative survival rate after their infection with Aeromonas hydrophila. The results showed that, compared with the control, in maggot meal and L - carnitine groups, some indices were significantly improved such as the weight gain and specific growth rates, the levels of total protein ( TP) , lysozyme ( LSZ) , complement 3 and 4 (C3 and C4) ,glutathione peroxidase (GSH -Px) in serum and the activities of superoxide dis-mutase (SOD) ,CSH - Px and catalase ( CAT) in liver (P 0. 05). The other indices, such as serum glutamic - pyruvic transaminase (GPT) and glutamic - oxaloacetic transaminase (GOT),survival rates,the fish physical indices and muscle composition were not significantly different among the three groups (P >0. 05). The challenge experiment with A. Hydrophila showed that the mortality of fish could be reduced in the maggot meal and L - carnitine groups compared with the control. Therefore, the diet supplemented with 25 g/kg maggot meal or 150 mg/kg L - carnitine could promote the growth of black carp, improve the non - specific immunity and antioxidation capacity and enhance fish resistance to disease.%研究蝇蛆粉和L-肉碱对青鱼(Mylopharyngodon piceus)生长、非特异性免疫和抗氧化能力的影响.选取初始体重(72.23 ±1

  18. Clinical Observation of L-carnitine Combined with Erythropoietin in the Treatment of Hemodialysis Patients with Anemia%左卡尼汀联合促红细胞生成素改善维持性血透患者贫血的临床分析

    Institute of Scientific and Technical Information of China (English)

    高建民; 陈伟; 徐燕; 陶润

    2015-01-01

    目的 分析左卡尼汀联合促红细胞生成素改善维持性血透患者贫血的临床结果. 方法 随机抽选2011年4月-2013年5月,该院接收维持性血透贫血患者60例,按入院顺序分成两组(实验组、对照组),对照组患者血液透析结束后给予促红细胞生成素,实验组在该基础上添加左卡尼汀,比对两组患者临床结果. 结果 实验组患者血红蛋白、红细胞压积水平、促红细胞生成素用量、高血压疾病病发率和对照组相比,差异有统计学意义(P<0.05). 结论 维持性血透患者贫血治疗期间联合使用左卡尼汀、促红细胞生成素,效果突出,可改善患者血红蛋白、红细胞压积水平,减少药物使用量,值得临床积极推广使用.%Objective To analyze the clinical results of combined L-carnitine and erythropoietin treatment of hemodialysis patients with anemia. Methods Decimation in April 2011 to may 2013. In our hospital received maintenance hemodialysis anemia patients 60 cases, according to the order of admission into two groups (experimental group and control group), the control group patients af-ter dialysis treated with erythropoietin, the experimental group on the basis of added L-carnitine, two groups of patients with clini-cal results comparison. Results Hemoglobin, red blood cell blood pressure product, erythropoietin dosage, and hypertension inci-dence were significantly different between the experimental group and the control group (P<0.05). Conclusion Maintenance hemodialysis patients with anemia combined with levocarnitine and erythropoietin (EPO) element, the effect is prominent, improve-ments in patients with hemoglobin and red blood cell pressure level of product, reduce the dosage of the drug, worthy of clinical and actively promote the use of.

  19. 高效液相色谱法测定牡蛎大豆肽肉碱口服液中维生素B6含量的不确定度评定%Uncertainty evaluation of determination of vitamin B6 content in oyster soybean peptide carnitine oral liquid by high per- formance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    庞学斌; 张伟; 邱颖姮; 邬晓鸥

    2015-01-01

    Objective Uncertainty evaluation of determination of vitamin B6 content in oyster soybean peptide carnitine oral liquid by high performance liquid chromatography(HPLC assay). Methods HPLC was adopted for the determination of vitamin B6 content. Mathematical model was established for the evaluation of uncertainty to quantize influential factors of uncertainty and evaluate the uncertainty factors further. Results The content of vitamin B6 in sample oral liquid was 0.498 mg/100mL,in which, the relative uncertaintyof vitamin B6 content was 0.024 9,the standard uncertainty was 0.0124 mg/100 mL,the expanded uncertainty was 0.024 8 mg/100 mL(k=2). Conclusion The calculation method is practical and reliable,being access to the uncertainty eval—uation of content of vitamin B6 in oyster soybean peptide carnitine oral liquid by high performance liquid chromatography. Upon the evaluation,it is found that the quantitative repetitive of the HPLC is the major impact.%目的:评定高效液相色谱法(HPLC法)测定牡蛎大豆肽肉碱口服液中维生素B6含量的不确定度。方法采用HPLC法测定试样中维生素B6的含量,根据建测量模型,确定影响不确定度的分量,并加以评定量化,得出合成不确定度和扩展不确定度。结果试样中维生素B6含量测得值为0.498 mg/100 mL,其中B6含量的相对不确定度为0.0249,标准不确定度为0.0124 mg/100 mL,扩展不确定度为0.0248 mg/100 mL(k=2)。结论建立的计算方法实用、可靠,可以用于HPLC法测定牡蛎大豆肽肉碱口服液中维生素B6含量的不确定度评定,经评定发现,高效液相色谱仪定量重复性对不确定度的影响最大。

  20. Expression of a cDNA isolated from rat brown adipose tissue and heart identifies the product as the muscle isoform of carnitine palmitoyltransferase I (M-CPT I). M-CPT I is the predominant CPT I isoform expressed in both white (epididymal) and brown adipocytes.

    Science.gov (United States)

    Esser, V; Brown, N F; Cowan, A T; Foster, D W; McGarry, J D

    1996-03-22

    We set out to determine if the cDNA encoding a carnitine palmitoyltransferase (CPT)-like protein recently isolated from rat brown adipose tissue (BAT) by Yamazaki et al. (Yamazaki, N., Shinohara, Y., Shima, A., and Terada, H. (1995) FEBS Lett. 363, 41-45) actually encodes the muscle isoform of mitochondrial CPT I (M-CPT I). To this end, a cDNA essentially identical to the original BAT clone was isolated from a rat heart library. When expressed in COS cells, the novel cDNA and our previously described cDNA for rat liver CPT I (L-CPT I) gave rise to products with the same kinetic characteristics (sensitivity to malonyl-CoA and Km for carnitine) as CPT I in skeletal muscle and liver mitochondria, respectively. When labeled with [3H]etomoxir, recombinant L-CPT I and putative M-CPT I, although having approximately the same predicated masses (88.2 kDa), migrated differently on SDS gels, as did CPT I from liver and muscle mitochondria. The same was true for the products of in vitro transcription and translation of the L-CPT I and putative M-CPT I cDNAs. We conclude that the BAT cDNA does in fact encode M-CPT I. Northern blots using L- and M-CPT I cDNA probes revealed the presence of L-CPT I mRNA in liver and heart and its absence from skeletal muscle and BAT. M-CPT I mRNA, which was absent from liver, was readily detected in skeletal muscle and was particularly strong in heart and BAT. Whereas the signal for L-CPT I was more abundant than that for M-CPT I in RNA isolated from whole epididymal fat pad, this was reversed in purified adipocytes from this source. These findings, coupled with the kinetic properties and migration profiles on SDS gels of CPT I in brown and white adipocytes, indicate that the muscle form of the enzyme is the dominant, if not exclusive, species in both cell types.

  1. Effects of dietary L-carnitine on growth, fat content and biochemical indexes of blood of tilapia (Oreochromis niloticus×Oreochromis aureus)%L-肉碱对奥尼罗非鱼生长、脂肪含量及血浆相关生化指标的影响

    Institute of Scientific and Technical Information of China (English)

    黄凯; 陈涛; 战歌; 麻艳群; 于丹; 蒋焕超

    2010-01-01

    取奥尼罗非鱼(Oreochromis niloticus×Oreochromis aureus)750尾,随机分为5组(每组150尾),分别饲喂添加0、50、100、150和200 mg/kg L-肉碱(L-carnitine)的饲料,以研究L-肉碱对奥尼罗非鱼生长、脂肪含量及血浆相关生化指标的影响,饲养周期为65 d.结果表明:饲料中肉碱添加量为150 mg/kg时,奥尼罗非鱼增重率和肥满度分别较对照组高19.91%和8.42%(P0.05);血浆中的胆固醇、甘油三酯含量分别降低9.82%(P>0.05)和65.43%(P0.05);白蛋白升高37.19%(P<0.05).在本研究条件下,建议奥尼罗非鱼饲料中L-肉碱添加量为150 mg/kg.

  2. Effects of L-carnitine on Egg Quality and Antioxidative Ability of Laying Hens Fed Diets Supplemented with Sunflower Oil%L-肉碱对饲粮中添加葵花油的产蛋鸡抗氧化功能及鸡蛋品质的影响

    Institute of Scientific and Technical Information of China (English)

    徐少辉; 张亚男; 武书庚; 张海军; 齐广海

    2011-01-01

    本试验旨在探讨L-肉碱和葵花油对产蛋鸡生产性能、抗氧化功能和鸡蛋品质的影响.选用288只产蛋率和体重相近、健康的27周龄海兰褐产蛋鸡,随机分成4组,每组6个重复,每个重复12只鸡.对照组试鸡饲喂基础饲粮,试验组试鸡分别饲喂在基础饲粮中添加3%葵花油、3%葵花油+200 mg/kg L-肉碱和3%葵花油+400 mg/kgL-肉碱的饲粮.试验期6周.结果表明:1)饲粮中添加L-肉碱和葵花油对产蛋鸡的生产性能影响不显著(P>0.05).2)与对照组相比,饲粮中添加3%葵花油显著降低第6周鸡蛋哈夫单位(P<0.05),添加L-肉碱可缓解葵花油造成的哈夫单位的下降;葵花油对第6周鸡蛋蛋壳强度无显著影响(P>0.05),与对照组相比,L-肉碱显著提高了第6周鸡蛋蛋壳强度(P<0.05)并有提高蛋白高度的趋势(P=0.06).3)与对照组相比,饲粮中添加3%葵花油显著降低第6周蛋鸡血清总抗氧化能力(T-AOC)(P<0.05),添加L-肉碱缓解了因葵花油而造成的T-AOC的下降;葵花油使得第6周蛋鸡血清丙二醛(MDA)含量显著升高(P<0.05),添加L-肉碱可缓解添加葵花油导致的MDA含量的升高;葵花油对血清超氧化物歧化酶(SOD)活性无显著影响(P>0.05),但显著提高了血清谷胱甘肽过氧化物酶(GSH-Px)活性(P<0.05),饲粮中添加400 mg/kg L-肉碱后,显著提高了第6周蛋鸡血清SOD活性(P<0.05),但对血清GSH-Px活性无显著影响(P>0.05).结果提示,饲粮中添加3%葵花油降低了蛋鸡蛋品质,影响了机体抗氧化能力,添加L-肉碱可改善鸡蛋品质并提高蛋鸡的抗氧化功能.%The objective of this study was to investigate the effects of L-carnitine and sunflower oil (SFO) on performance, egg quality and antioxidative ability of laying hens. A total of two hundred and eighty eight 27-week-old healthy Hyline laying hens with similar egg production rate and weight were selected as experimental animals and divided

  3. L-肉碱强化卤虫对草鱼、鳙鱼和鲤鱼开口苗中长链脂肪酸组成的影响%Effects of L-carnitine enriched Artemia on medium and long chain fatty acids composition in first feeding larvae of grass carp,bighead carp and common carp,Ctenopharyngodon idella,Aristichysn obilis,Cyprinus carpio

    Institute of Scientific and Technical Information of China (English)

    陈玉珂; 蔺丽丽; 宋丹; 裴怀全; 朱成成; 张东鸣

    2012-01-01

    【目的】研究L-肉碱强化卤虫对草鱼、鳙鱼和鲤鱼开口苗中长链脂肪酸组成的影响。【方法】用0(对照,CK),1,100,1 000 mg/L的L-肉碱分别强化卤虫无节幼体(Artemia sp.)12 h,投喂3种鱼开口苗21 d,测定鱼开口苗体内的脂肪酸含量,分析中长链脂肪酸(C14-C24)的组成。【结果】草鱼和鳙鱼开口苗的1和100 mg/L处理组的C18∶2n-6、C18∶3n-3、C20∶4n-6、DHA和EPA含量较对照组显著增加(P<0.05);3种鱼开口苗的1 mg/L处理组的C14-C24脂肪酸总含量、饱和脂肪酸和单不饱和脂肪酸含量较其他3组大多显著降低(P<0.05);草鱼和鳙鱼开口苗的100 mg/L处理组的多不饱和脂肪酸、n-3+n-6族脂肪酸以及DHA+EPA含量较对照组显著升高(P<0.05);L-肉碱强化的卤虫对鲤鱼开口苗多不饱和脂肪酸、n-3+n-6族脂肪酸及DHA+EPA含量没有显著影响(P>0.05)。【结论】在本试验条件下,以100 mg/L L-肉碱强化卤虫无节幼体投喂鱼开口苗,可显著改善草鱼和鳙鱼开口苗的中长链脂肪酸组成,但对鲤鱼开口苗中长链脂肪酸组成的影响较小。%【Objective】Effects of L-carnitine enriched Artemia on medium and long chain fatty acids composition in first feeding larvae of three freshwater fish were studied.【Method】The experimental larvae were reared in a 50 L tank with stocking density of 40 fish/L at(25±1) ℃ for 21days.The newly hatched Artemia nauplii,enriched with 4 levels(0,1,100,1000 mg/L)of L-carnitine at(25±1) ℃ for 12 h,were used as starter food for rearing larvae.The medium and long chain fatty acids composition(C14-C24)in the experimental larvae were determined by GC and evaluated.【Result】Linoleic acid,linolenic acid,arachidonic acid,EPA and DHA content were significantly(P〈0.05)improved by feeding 1and 100 mg/L L-carnitine enriched nauplii than the control group in the first feeding larvae of grass carp

  4. Influence of L-carnitine on the Content of H-FABP and cTnI in Patients with Acute Myocardial Infarction after PCI%左卡尼汀对急性心肌梗死PCI术患者血清H-FABP和cTnI水平的影响

    Institute of Scientific and Technical Information of China (English)

    张科芝

    2015-01-01

    目的:探讨左卡尼汀对急性心肌梗死急诊行PCI治疗患者血浆心型脂肪酸结合蛋白(H-FABP)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)水平的影响。方法:选取笔者所在医院2012年11月-2014年12月收诊的100例急性心肌梗死患者作为研究对象,按照随机数字表法将其分为治疗组和对照组,每组50例。对照组按心血管指南行急诊PCI治疗,治疗组在此治疗基础上加用左卡尼汀3.0 g+0.9%氯化钠注射液250 ml静脉滴注(术中),以后1次/d,连续7 d。检测两组患者PCI术前及PCI术后6、12、24、48 h的血浆H-FABP、CK-MB、cTnI数值。结果:治疗组血浆H-FABP、CK-MB、cTnI水平在术后相同时间点均较对照组降低,差异均有统计学意义(P<0.05)。行PCI术患者术后6 h血浆H-FABP明显高于术前(P<0.05),24 h恢复至术前水平。结论:左卡尼汀对缺血再灌注心肌细胞有保护作用,检测H-FABP有利于早期判断患者的心肌损伤,以便及早干预。%Objective:To investigate the curative effect of L-carnitine on the content of heart fatty acid binding protein(H-FABP),creatine kinase isoenzyme-MB(CK-MB) and myocardial troponin(cTnI) in acute myocardial infarction(AMI) patients with PCI.Method:A total of 100 AMI patients with PCI admitted to our hospital from November 2012 to December 2014 were selected as research objects,they were divided into the treatment group and the control group according to the random number table method,50 cases in each group.The control group was treated with routine therapy,the treatment group was treated with Levocarnitine 3 g+physiological saline 250 ml intravenous drip every day on the basis of above routine treatment for seven days.The H-FABP,CK-MB,cTnI in plasma of AMI Patients with PCI were detected before and after PCI 6,12,24,48 h.Result:The H-FABP, CK-MB,cTnI levels in plasma of the treatment group at the same point of time after operation were significantly

  5. 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

  6. Study on Anti-obesity and Lipid-lowering of Chinese Medicine Xianti Formula with L-carnitine Tartrate Salt%中药纤体组方加左旋肉碱酒石酸盐减肥降脂作用实验研究

    Institute of Scientific and Technical Information of China (English)

    操红缨; 李萍; 刘静

    2012-01-01

    Objective : To investigate effects of anti-obesity and lipid-lowering of Chinese medicine Xianti formula ( XTA ) and XTA with 1-carnitine tartrate salt ( XTB ) in niutritional obesity rats model. Methods : Made obesity model with high fat food, through observing body weight, food intake, food utilization, fat weight, body fat ratio; serum triglyceride ( TG ), total cholesterol ( TC ), high-density lipoprotein ( HDL-C ), low density lipoprotein ( LDL-C ) levels to assess effects of losing weight and lowering lipid of test samples. Results : Body weight of high fat feed group rats significant higher than normal group, tip that obesity model made successfully. Compared with model group, XTA high dose group rats'body weight significantly reduce ( P<0.05 ), food utiliazation of low and medium dose group all reduced ( P<0.05 ),low,medium and high dose group rats' fat weight and body fat ratio significantly reduced( P<0.05 ) Compared with model group, XTB middle and high dose group rats' body weight significantly reduced ( P<0.05 ), food utiliazation of low and high dose group all reduced ( P<0.05 ) low, medium and high dose group rats' fat weight and body fat ratio significantly reduced ( P<0.01~0.05 ); XTA medium and high doses group, XTB low, medium and high dose groups'serum TG were significantly lower ( P<0.05 ); LDL-C of XTB high dose group rats lower, but its HDL-C significantly rise ( P<0.05 ). Conclusion: XTA and XTB can lose weight through inhibiting nutritional obesity rat growth, lower fat weight and food utilization, and also have the effect of regulating blood lipid.Further more, there is a trend that XTB better than XTA., tip that Chinese medicine Xianti formula add 1-carnitine tartrate salt can enhance its effects of anti-obesity and lipid-Lowering.%目的:探讨中药纤体组方(XTA)和中药纤体组方加左旋肉碱酒石酸盐(XTB)对营养性肥胖大鼠减肥降脂的作用.方法:利用高脂饲料饮食建立营养性肥胖大鼠模型,通过

  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. Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

    Science.gov (United States)

    ... deficiency Related Information How are genetic conditions and genes named? ... Boneh A, Dweikat I, Zater M, Meiner V, Gutman A, Brivet M. A novel SLC25A20 splicing mutation in patients of different ethnic origin with ...

  9. Effects of fenofibrate on gene expression of carnitine palmitoyltransferase 1 in liver and skeletal muscle and its influence on insulin sensitivity%非诺贝特对肝脏和肌肉肉毒碱脂酰转移酶1基因表达及胰岛素敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    白秀平; 李宏亮; 杨文英; 萧建中; 王冰; 杜瑞琴; 楼大钧

    2008-01-01

    Objective To study the effects of fenofibrate (FF),a peroxisome proliferator activated receptor (PPAR)α activator,on the expression of carnitine palmitoyltransferase 1 (CPT-1) mRNA in liver and muscle and its influence on insulin sensitivity.Methods Thirty-two normal 8 week-old male SD rats were randomly divided into 3 groups:normal control group,fed with normal food for 3 weeks (NC group,n=10),high fat diet group,fed with high fat food (HF group,n=10),and high fat diet supplemented group,n=12).Fast serum triglyceride (TG) level was tested by automatic biochemical analyzer after 8~10 h fasting.Euglycemic-hyperinsulinemic clamp method was used to calculate the glucose infusion rate (GIR) so as to evaluate the insulin sensitivity.By the end of experiment the rats were killed with their internal organs taken out.The triglyceride (TG) contents of liver and skeletal muscle were measured using Folch method.Real-time PCR was used to detect the mRNA expression.of CPT-1 in the liver and skeletal muscles.Results As compared with the NC group.the TG levels of serum,liver,and skeletal muscle of the HF group were higher than those of the NC group by 0.45-fold,2.14-fold,and 10.64-fold respectively.liver of the HF group was not significantly different from that of the NC group(P>0.05);the expression of CPT-1 mRNA in skeletal muscle of the HF group was lower than that of the NC group by 71%(P<0.01).The CPT-1 mRNA expression in liver and skeletal muscle of the FF group were significantly higher than those of the HF group by 1.00 and 1.05 times respectively(both P<05).The GIR was negatively correlated with the levels in the liver(r=-0.87.P<0.01)and in the skeletal muscle (r=-0.78,P<0.01).Conclusion Fenofibrate promotes the oxygenation of fatty acids by up-regulating the CPT-1 mRNA expression in the liver and skeletal muscles,thus improving the insulin sensitivity.%目的 探讨非诺贝特对肝脏、肌肉肉毒碱脂酰转移酶1表达及胰

  10. 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…

  11. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder

    OpenAIRE

    Frye, R E; Melnyk, S; MacFabe, D F

    2013-01-01

    Autism spectrum disorder (ASD) has been associated with mitochondrial disease (MD). Interestingly, most individuals with ASD and MD do not have a specific genetic mutation to explain the MD, raising the possibility of that MD may be acquired, at least in a subgroup of children with ASD. Acquired MD has been demonstrated in a rodent ASD model in which propionic acid (PPA), an enteric bacterial fermentation product of ASD-associated gut bacteria, is infused intracerebroventricularly. This anima...

  12. 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 standar

  13. Effect of exogenous proline, betaine, and carnitine on growth of Listeria monocytogenes in a minimal medium.

    OpenAIRE

    Beumer, R. R.; te Giffel, M.C.; Cox, L.J.; Rombouts, F M; Abee, T

    1994-01-01

    Three Listeria monocytogenes strains isolated from food or food-processing environments were used to assess the response of this species to salinity in a chemically defined minimal medium. Growth in a minimal medium containing five essential amino acids and glucose as a carbon and energy source was comparable to growth in a rich medium (brain heart infusion broth). In the absence and presence of 3% NaCl the final cell numbers reached in minimal medium were 10(9) and 10(7) CFU/ml, respectively...

  14. Perinatal upregulation of intestinal transport of carnitine (C) in newborn pigs

    Energy Technology Data Exchange (ETDEWEB)

    Li, B.U.K.; Murray, R.D.; Heitlinger, L.A.; McClung, H.J.; Hughes, A.M.; O' Dorisio, T.M.; Sloan, H.R. (Columbus Children' s Hospital, OH (United States) Ohio State Univ., Columbus (United States))

    1990-02-26

    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{sub 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 ({sup 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.

  15. In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease

    NARCIS (Netherlands)

    Mescka, Caroline; Moraes, Tarsila; Rosa, Andrea; Mazzola, Priscila; Piccoli, Bruna; Jacques, Carlos; Dalazen, Giovana; Coelho, Juliana; Cortes, Marcelo; Terra, Melaine; Regla Vargas, Carmen; Dutra-Filho, Carlos S

    2011-01-01

    Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase (BCKAD) leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and val

  16. Prophylactic and Therapeutic Potential of Acetyl-L-carnitine against Acetaminophen-Induced Hepatotoxicity in Mice.

    Science.gov (United States)

    Alotaibi, Salman A; Alanazi, Abdulrazaq; Bakheet, Saleh A; Alharbi, Naif O; Nagi, Mahmoud N

    2016-01-01

    Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen-induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N-acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N-acetylcystiene in the treatment of acetaminophen toxicity.

  17. [COMPARISON OF FREE CARNITINE LEVELS WITH NUTRITIONAL STATUS IN INFANTILE NEPHROPATHYC CISTINOSIS PATIENTS].

    Science.gov (United States)

    Guillén-López, Sara; Ibarra-González, Isabel; Belmont Martínez, Leticia; Juárez-Cruz, Merit Valeria; Vela-Amieva, Marcela

    2015-12-01

    Introducción: la cistinosis nefropática infantil (CNI) es una enfermedad genética debida a un defecto del transporte de la cistina, con la subsecuente acumulación de este aminoácido predominantemente en el riñón. Existen pocos estudios sobre la evaluación del estado nutricional en pacientes con esta patología, pero se sabe que tienen una excreción de carnitina urinaria aumentada, lo que puede dar como resultado una deficiencia plasmática y muscular de este compuesto; sin embargo, la suplementación de carnitina en CNI es controversial. Objetivo: comparar la concentración sanguínea de carnitina libre (C0) con el estado nutricional de una cohorte de pacientes con CNI. Material y métodos: evaluación antropométrica mediante la medición de peso, talla, perímetro braquial (PB) y pliegue cutáneo tricipital (PCT). La C0 se cuantificó mediante espectrometría de masas en tándem en muestras de sangre en ayuno. Resultados: se analizaron 10 pacientes con CNI, 5 con y 5 sin trasplante renal. De acuerdo con el IMC, 3/10 presentaron desnutrición. La reserva de masa magra se encontró baja en 8/10 pacientes (3 no trasplantados y todos los trasplantados). El PB mostró correlación con las concentraciones sanguíneas de C0 (r2 = 0,353); Los pacientes no trasplantados tuvieron niveles de C0 significativamente más bajos que los trasplantados (Chi2 = 0,0027). Conclusión: en esta población de pacientes con CNI se encontró un 70% de sujetos con C0 baja, que se correlaciona con la masa magra disminuida. Es recomendable hacer una evaluación nutricional de rutina que incluya los tres parámetros antropométricos como parte del seguimiento médico-nutricional integral de estos pacientes.

  18. Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of partial carnitine palmityl transferase II deficiency

    OpenAIRE

    Rigante, Donato; Bersani, Giulia; Compagnone, Adele; Zampetti, Anna; Nisco, Alessia; Sacco, Emanuela; Marrocco, Raffaella

    2009-01-01

    Abstract We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term. The recurrence of rhabdomyolysis required a muscular biopsy showing a disturbance of fatty acid ?-oxidation p...

  19. Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of partial carnitine palmityl transferase II deficiency.

    Science.gov (United States)

    Rigante, Donato; Bersani, Giulia; Compagnone, Adele; Zampetti, Anna; De Nisco, Alessia; Sacco, Emanuela; Marrocco, Raffaella

    2011-06-01

    We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term. The recurrence of rhabdomyolysis required a muscular biopsy showing a disturbance of fatty acid β-oxidation pathway. PMID:19855973

  20. Characterization of in vitro models for evaluation of molecular mechanisms involved in the action of Acetyl-L-Carnitine

    OpenAIRE

    Lapa, Joana Filipa Ramos

    2014-01-01

    Pensa-se que a acetil-L-carnitina (ALC) tem ação neuroprotetora, principalmente por prevenir a disfunção mitocondrial no sistema nervoso central e periférico. A ALC é bem conhecida por afetar o metabolismo e a bioenergética do cérebro, e por isso é expetável que alguns dos mecanismos envolvidos na sua ação possam estar relacionados com o metabolismo e absorção de glucose. No entanto, os mecanismos subjacentes à ação da ALC não são ainda bem conhecidos. Os modelos celulares são ferramentas ...

  1. Variations in IBD (ACAD8) in children with elevated C-4-carnitine detected by tandem mass spectrometry newborn screening

    NARCIS (Netherlands)

    C.B. Pedersen; C. Bischoff; E. Christensen; H. Simonsen; A.M. Lund; S.P. Young; D.D. Koeberl; D.S. Millington; C.R. Roe; D.S. Roe; R.J.A. Wanders; J.P.N. Ruiter; L.D. Keppen; Q. Stein; I. Knudsen; N. Gregersen; B.S. Andresen

    2006-01-01

    The isobutyryl-CoA dehydrogenase (IBD) enzyme is involved in the degradation of valine. IBD deficiency was first reported in 1998 and subsequent genetic investigations identified acyl-CoA dehydrogenase (ACAD) 8, now IBD, as the gene responsible for IBD deficiency. Only three individuals homozygous o

  2. 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

    -CHO) or 2) a low-carbohydrate diet (L-CHO) before exercise to alter muscle glycogen content as well as to induce, respectively, low and high rates of fat oxidation. Leg fat oxidation was 122% higher during exercise in L-CHO than in H-CHO (P ...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...

  3. Discovery of a long-chain carbamoyl aminocarnitine derivative, a reversible carnitine palmitoyltransferase inhibitor with antiketotic and antidiabetic activity.

    Science.gov (United States)

    Giannessi, Fabio; Pessotto, Pompeo; Tassoni, Emanuela; Chiodi, Piero; Conti, Roberto; De Angelis, Francesco; Dell'Uomo, Natalina; Catini, Roberto; Deias, Roberto; Tinti, Maria Ornella; Carminati, Paolo; Arduini, Arduino

    2003-01-16

    The synthesis and pharmacological activity of reversible CPT I inhibitors as potential antiketotic and antidiabetic drugs are reported. Such inhibitors constitute a series of enantiomerically pure aminocarnitine derivatives having the general formula (CH3)3N+CH2CH(ZR)CH2COO- (with Z = ureido, carbamate, sulfonamide, and sulfamide moieties; R = C7-C14 linear alkyl chains). A primary pharmacological screening based on the evaluation of CPT I activity in intact rat liver (L-CPT I) mitochondria revealed the best activity for the (R) forms of ureidic derivative 17 (ZR = NHCONHR, R = C14), sulfonamidic derivative 7 (ZR = NHSO2R, R = C12), and sulfamidic derivative 9 (ZR = NHSO2NHR, R = C11). The IC50 values are 1.1, 0.7, and 0.8 microM, respectively. For the carbamic derivative 11 (ZR = NHCOOR, R = C8), an IC50 of 9.5 microM was observed. In addition, an extraordinarily high selectivity toward the liver isoform with respect to the heart isoform (muscle-CPT I identical with M-CPT I) was found for the ureidic compound 17 (IC50(M-CPT I) vs IC50(L-CPTI) = 39.4), as well as for other ureidic or carbamic compounds. Diabetic db/db mice treated orally with 17 and 7 for 45 days at a dose of 50 mg/kg twice a day showed a good reduction of serum glucose levels with respect to the untreated db/db mice (p < 0.01). In addition, 17 showed antiketotic activity in normal fasted rats. 17 has been selected for development as a potential antiketotic and antidiabetic drug. PMID:12519067

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

    OpenAIRE

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

    2014-01-01

    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.

  5. Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays.

    Science.gov (United States)

    Chen, Li; Wang, Jiaolong; Mouser, Glen; Li, Yan Chun; Marcovici, Geno

    2016-06-01

    Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd.

  6. 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

    the population frequency of this variant, we determined CPT1A p.P479L genotypes in 1111 Greenland Inuit. Associations between genotype and variation in plasma total cholesterol, triglycerides, LDL, HDL, apolipoprotein (apo) B, and apo A-I were also investigated. We found the L479 allele occurs at a high...... subsequently studied. However, CPT1A p.P479L was associated with elevated plasma HDL and apo A-I levels. The association with increased levels of HDL and apo A-I suggest that the polymorphism might protect against atherosclerosis....

  7. 补充L-肉碱在运动训练中的研究进展%The research progress on supplement L-carnitine during sports training

    Institute of Scientific and Technical Information of China (English)

    赵奋军; 余小燕

    2008-01-01

    采用文献资料法,介绍了L-肉碱的生理功能.运动训练对L-碱的影响,以及L-肉碱对不同形式运动能力的影响.综述了L-肉碱在运动训练中的研究现状及该领域研究中存在的问题,L-肉碱在运动训练中的研究意义,将来值得研究的方向.以此为补充左旋肉碱在提高运动能力中的应用提供一定的理论依据.

  8. Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet.

    Directory of Open Access Journals (Sweden)

    Gaetano Serviddio

    Full Text Available There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH. The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I, the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.

  9. Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays.

    Science.gov (United States)

    Chen, Li; Wang, Jiaolong; Mouser, Glen; Li, Yan Chun; Marcovici, Geno

    2016-06-01

    Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26990224

  10. 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...

  11. Metabolomic Research on Newborn Infants With Intrauterine Growth Restriction

    Science.gov (United States)

    Liu, Jing; Chen, Xin-Xin; Li, Xiang-Wen; Fu, Wei; Zhang, Wan-Qiao

    2016-01-01

    Abstract To compare differences in metabolites between newborns with intrauterine growth restriction (IUGR) and those who are appropriate for gestational age (AGA) in order to understand the changes in metabolites of newborns with IUGR and to explore the possible metabolic mechanism of tissue and organ damages in patients with IUGR, with the ultimate goal of providing the basis for clinical intervention. A total of 60 newborns with IUGR and 60 AGA newborns who were hospitalized in the neonatal intensive care unit of our hospital between January 2011 and December 2015 and who underwent metabolic disease screening were enrolled in this study. The differences in 21 amino acids and 55 carnitines in peripheral blood, as well as changes in the ratios of free carnitine and acylcarnitine to total carnitine, were compared. Metabolites, particularly alanine, homocysteine, leucine, methionine, ornithine, serine, tyrosine, isovaleryl carnitine, and eicosenoyl carnitine, differed according to newborns’ birth weight (<3rd percentile, 3rd–5th percentiles, 5th–10th percentiles, and 10th–90th percentiles), with those with lower birth weight showing the greater difference (P < 0.05). Metabolites also differed by gestational age, and the differences observed were mainly as follows: preterm and full-term newborns showed differences in metabolites, mainly in alanine, proline, cerotoyl carnitine, and tetradecanedioyl carnitine (P < 0.05); preterm and full-term AGA newborns showed differences in metabolites, mainly in alanine, glutamine, homocysteine, pipecolic acid, proline, heptanoyl carnitine, and sebacoyl carnitine (P < 0.05); and preterm and full-term newborns with IUGR showed differences in metabolites, mainly in arginine, glutamic acid, homocysteine, histidine, leucine, isoleucine, ornithine, serine, threonine, tryptophan, valine, heptanoyl carnitine, decanoyl carnitine, linoleyl carnitine, methylmalonyl carnitine, glutarylcarnitine, sebacoyl carnitine

  12. L-carnitine prevents gentamicin-induced impairment of hair cell in newborn guinea pigs%L-肉碱对庆大霉素致子代豚鼠毛细胞损伤干预作用

    Institute of Scientific and Technical Information of China (English)

    郝帅; 田颖; 姜菲菲; 姜学钧

    2012-01-01

    Objective To evaluate the role of L-camitine(LCAR) supplementation in hearing threshold and cochlear damage in newborn guinea pigs exposed to gentamicin in utero. Methods Pregnant albino guinea pigs were intraperitoneally injected with 100 mg/kg body weight gentamicin once a day for 7 consecutive days,or gentamicin and LCAR at gestational day 51 to 57. At postnatal day 14,the pups were examined in the distortion product otoacoustic emission( DPOAE) task. The temporal bones were immunohistochemically stained for caspase-3, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) method. Results Gentamicin used during pregnancy decreased the DPOAE threshold shifts at different frequencies of 1,2,4,5,and 8 kHz(8. 38 ±2. 28,12. 56 ±3.22,10.46 ± 1. 98,12. 22 ± 1.72,and 17.73 ±2. 16 dB,respectively). In contrast,LCAR supplementation,coincidentally with gentamicin exposure,ameliorated these changes( 14. 26 ±1.47,20. 98 ±2. 39,19. 23 ±2. 15,22.56 ± 1. 41,and 29. 13 ±3. 14 dB,respectively). In addition, gentamicin used during pregnancy increased the percentage of apoptotic cells in hair cells( 34.6% ), but LCAR supplementation decreased the percentage of apoptotic cells( 15.1% ,P <0. 05). Conclusion Our data offer a conceptual framework for designing clinical trials using a safe nutrient,LCAR,as a simple preventive strategy for gentamicin-induced ototoxicity.%目的 观察围产期L-肉碱对庆大霉素暴露致子代豚鼠听力损伤及耳蜗毛细胞凋亡的影响.方法 将18只孕中期豚鼠按体重随机分为3组,从孕51 ~57 d,对照组腹膜内注射生理盐水100 mg/kg、庆大霉素组腹膜内注射庆大霉素100 mg/kg,L-肉碱组腹膜内注射庆大霉素100 mg/kg同时以饮水方式给予L-肉碱100 mg/mL;出生后14 d,检测子代豚鼠畸变产物耳声发射(distortion product otoacoustic emission,DPOAE)改变,应用原位末端转移酶标记技术(TUNEL)染色和免疫组化检测毛细胞凋亡情况.结果 围产期庆大霉素暴露致子代豚鼠DPOAE幅值在频率1、2、4、6、8kHz下分别为(8.38±2.28)、(12.56±3.22)、(10.46±1.98)、(12.22±1.72)、(17.73±2.16)dB,L-肉碱组在相同频率下DPOAE幅值分别为(14.26±1.47)、(20.98±2.39)、( 19.23±2.15)、(22.56±1.41)、(29.13±3.14)dB;庆大霉素暴露致子代豚鼠耳蜗毛细胞凋亡率为34.6%,L-肉碱可降低毛细胞凋亡率至15.7% (P <0.05).结论 L-肉碱对庆大霉素致子代豚鼠耳毒性具有干预作用.

  13. 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

    OpenAIRE

    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.

    2010-01-01

    OBJECTIVE 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. RESEARCH DESIGN AND METHODS Mitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-r...

  14. Efect of L-Carnitine on Protein Digestibility of Diet of Common Carp%肉毒碱对鲤夏花鱼种饲料蛋白质消化率的影响

    Institute of Scientific and Technical Information of China (English)

    路桥; 董静; 王绍露; 吕玲; 陈勇

    2008-01-01

    用分别添加了0、50、100、150、200、250mg/kg饲料纯肉毒碱的饲料饲养相同的鲤夏花鱼种,比较其对每种饲料蛋白质的消化率.结果表明:肉毒碱具有明显的促进鲤饲料蛋白质消化的作用,并且添加量在100mg/kg时促消化作用最好.

  15. Effects of Levocarnitine on Brachial-Ankle Pulse Wave Velocity in Hemodialysis Patients: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Terumi Higuchi

    2014-12-01

    Full Text Available Background and Aims: Atherosclerotic cardiovascular disease is the most common cause of mortality in patients with end-stage kidney disease. Chronic kidney disease patients often exhibit a deficiency in l-carnitine due to loss during hemodialysis (HD. We studied the effects of l-carnitine supplementation on brachial-ankle pulse wave velocity (baPWV, a marker of atherosclerosis, in HD patients. Methods: This was a prospective, open-label, randomized, parallel controlled, multi-center trial testing the anti-atherosclerotic efficacy of oral l-carnitine administration (20 mg/kg/day. HD patients (n = 176, mean age, 67.2 ± 10.3 years old; mean duration of HD, 54 ± 51 months with plasma free l-carnitine deficiency (<40 μmol/L were randomly assigned to the oral l-carnitine group (n = 88 or control group (n = 88 and monitored during 12 months of treatment. Results: There were no significant differences in baseline clinical variables between the l-carnitine and control groups. l-carnitine supplementation for 12 months significantly increased total, free, and acyl carnitine levels, and reduced the acyl/free carnitine ratio. The baPWV value decreased from 2085 ± 478 cm/s at baseline to 1972 ± 440 cm/s after six months (p < 0.05 to 1933 ± 363 cm/s after 12 months (p < 0.001 of l-carnitine administration, while no significant changes in baPWV were observed in the control group. Baseline baPWV was the only factor significantly correlated with the decrease in baPWV. Conclusions: l-carnitine supplementation significantly reduced baPWV in HD patients. l-carnitine may be a novel therapeutic strategy for preventing the progression of atherosclerotic cardiovascular disease.

  16. Usefulness of Levocarnitine and/or Branched-Chain Amino Acids during Invasive Treatment for Hepatocellular Carcinoma.

    Science.gov (United States)

    Iwasa, Motoh; Sugimoto, Ryosuke; Ishihara, Tomoaki; Sekoguchi-Fujikawa, Noriko; Yoshikawa, Kyoko; Mifuji-Moroka, Rumi; Tanaka, Hideaki; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

    2015-01-01

    Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (L-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine+BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine+BCAA and BCAA-alone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb. PMID:26875483

  17. 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.

  18. Suplementación con carnitina para perder peso: Una aproximación bioquímica

    Directory of Open Access Journals (Sweden)

    José Henry Osorio

    2011-11-01

    Full Text Available Carnitine is a molecule involved in transporting activated fatty acids among different cellular compartments, which is most likely present in all animal species, and in numerous microorganisms and plants. Recently the trend in the field of weight control is to include carnitine in the diet as an agent responsible for weight loss. In the present review, some findings are discussed from a biochemical point of view to illustrate if the use of carnitine for weight loss can be considered fiction or reality.

  19. An Open-label Phase 2 Study of UX007 (Triheptanoin) in Subjects With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

    Science.gov (United States)

    2015-12-15

    Long-chain Fatty Acid Oxidation Disorders (LC-FAOD); Carnitine Palmitoyltransferase (CPT II) Deficiency; Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency; Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency; Trifunctional Protein (TFP) Deficiency

  20. Influence of L-carnitine in Elderly Patients with Maintenance Hemodialysis and Nutritional Status of Lipids%左卡尼汀对老年维持性血液透析患者血脂及营养情况的影响

    Institute of Scientific and Technical Information of China (English)

    谢鸣部; 潘淼; 王芳; 李大勇; 刘小华; 陈晶; 黄智敏

    2013-01-01

    Objective:To study the impact of levocarnitine on lipid profile and malnutrition in elderly maintenance hemodialysis (MHD). Methods: 72 elderly patients on MHD were randomly divided into treatment group and control group. The treatment group was given levocarnitine 1g by intravenous injection at the end of each hemodialysis. The duration oftherapy was six months. The control group was given physiological saline by intravenous injection at the end of each hemodialysis. The frequency and duration of therapy were the same in the two groups. Total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein serum albumin, prealbumin, transferring, and hemoglobin were measured. Results: Total cholesterol, triglyceride, low density lipoprotein were reduced in treatment group compared with control group (P <0.05). Serum albumin, prealbumin, transferring, and hemoglobin were increased in treatment group compared with control group ( P < 0. 05). Conclusions:Levocarnitine can significantly improve malnutrition and lipid profile function in elderly hemodialysis patients.%目的:观察应用左卡尼汀对老年维持性血液透析( maintenance hemodialysis,MHD)患者血脂及营养情况的影响。方法将72例老年MHD患者随机分为治疗组和对照组,治疗组于每次血液透析结束前从静脉缓慢注入左旋肉碱1g 加生理盐水20 ml,共6个月。对照组于结束前静脉注入生理盐水20 ml,频次及疗程同治疗组,疗程共6个月。比较两组治疗前后患者的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、血清白蛋白(ALB)、前白蛋白(PAB)、转铁蛋白(TF)、血红蛋白(HGB)水平。结果治疗组经左旋肉碱治疗6个月后,与治疗前及对照组比较,TG、CHO、LDL水平下降,ALB、PAB、TF、Hb水平上升,其差异有统计学意义(均P<0.05)。结论左旋肉碱可改善老年维持性血液透析的血脂异常和营养不良。

  1. 左卡尼汀联合促红细胞生成素治疗肾性贫血的疗效比较分析%L-carnitine joint erythropoietin production treatment comparative analysis of the efficacy of renal anemia

    Institute of Scientific and Technical Information of China (English)

    刘金平

    2016-01-01

    目的 观察左卡尼汀联合促红细胞生成素治疗肾性贫血的临床疗效.方法 选取我院2013年10月~2014年10月收治的慢性肾衰竭并发肾性贫血患者60例,将其分为治疗组和对照组各30例.两组患者均在血液透析治疗过程中给予皮下注射促红细胞生成素进行治疗,同时辅以口服铁剂、叶酸和VitB12等进行对症治疗,治疗组在此基础上联合应用左卡尼汀进行治疗.观察比较两组在血红蛋白(Hb)、血细胞比容(Hct)变化水平和促红细胞生成素(rhuEPO)用量等方面的指标变化.结果 两组患者治疗后Hb和Hct均明显升高;治疗组患者在维持患者Hb和Hct开始水平的情况下,其rhuEPO的用量不断减少,对照组患者rhuEPO用量无明显变化;治疗组患者临床治疗总有效率92.0%,明显高于对照组(74.0%);治疗组不良反应发生率显著低于对照组(P<0.05).结论 左卡尼汀联合促红细胞生成素治疗肾性贫血能够显著提高患者的临床治疗效果,且不良反应较少.

  2. 苯丙酮尿症患儿微量营养素、氨基酸、肉碱营养状况的研究%Nutritional state analysis of micronutrient, mino acids and carnitine in children with phenylketonuria treated with dietotherapy.

    Institute of Scientific and Technical Information of China (English)

    张立琴; 苏乃仑; 赵彩红; 傅平

    2011-01-01

    [Objective] To analysis nutritional problem in children with phenylketonuria treated with dietotherapy,so as to provide a basis for intervention.[Methods] 46 children with phenylketonuria detected by neonatal screening in Qingdao were studied and compared to 61 matched normal children born at the same time. Nutritional state of the children was evaluated on the blood biochemical parameters,analysis of amino acids in serum respectively. [Results] Dthe blood Zn,Cu in children with phenylketonuria were lower than those of the normal controls(P0. 05). [Conclusions] The present findings strongly suggest that there were nutrient deficiencies in children with phenylketonuria, though having been early-diagn6sed and early-treated. Timely identification and correction of the nutrient deficiencies in children with phenylketonuria are important. To seek the best treatment program is the direction of our efforts.%[目的]研究低苯丙氨酸饮食治疗的苯丙酮尿症( phenylketonuria,PKU)儿童饮食治疗过程中微量营养素、氨基酸、肉碱的营养状况,为寻求其最佳治疗方案提供依据. [方法]选取1997年12月-2005年6月经青岛市新生儿疾病筛查中心确诊的PKU患儿46例作为病例组,选取性别、年龄与病例组匹配、无任何躯体及精神疾病的正常儿童61例作为对照组,对所有病例进行血常规、微量元素、氨基酸和肉碱检测. [结果]1)两组儿童血锌、铜含量的差异有统计学意义(P<0.05),且病例组儿童锌缺乏明显多于对照组(x2=7.017,P=0.008);2)两组儿童血液中天冬氨酸、甲硫氨酸、苯丙氨酸、精氨酸、瓜氨酸、甘氨酸、鸟氨酸含量的差异均有高度统计学意义(P<0.01).3)游离肉碱、乙酰基肉碱、丙酰基肉碱、丁酰基肉碱的差异均无统计学意义(P>0.05). [结论]经新生儿疾病筛查得到早期诊断,早期进行常规饮食治疗的PKU患儿仍然存在某些微量营养素缺乏,治疗过程中氨基酸、肉碱虽在正常范围之内,但仍低于正常儿童.因此,必须定期对低苯丙氨酸饮食治疗的PKU的患儿进行氨基酸、肉碱的监测,及时发现并纠正PKU儿童所存在的营养偏差,寻求PKU儿童最佳的饮食治疗方案.

  3. Estrategias de ingeniería metabólica y biología de sistemas aplicadas a la producción de L(-)carnitina por Escherichia coli= Metabolic engineering and systems biology strategies for L(-)carnitine production in Escherichia coli

    OpenAIRE

    Arense Parra, Paula

    2014-01-01

    Esta Tesis Doctoral recoge el trabajo de investigación que se ha realizado en dos líneas desarrolladas de forma paralela sobre Escherichia coli. Por un lado, la optimización de un proceso de biotransformación para mejorar la síntesis de L( )-carnitina mediante técnicas de ingeniería metabólica. Y por otro, la determinación de los principales efectos que provoca la exposición prolongada a altas concentraciones de sal y su respuesta de adaptación, principalmente cuando las fuentes de carbono pu...

  4. Lipid storage myopathies with unusual clinical manifestations

    Directory of Open Access Journals (Sweden)

    Uppin Megha

    2008-01-01

    Full Text Available We describe the clinical presentation, course and pathologic findings found in three adult patients with lipid storage myopathy. Excessive lipid storage was found in Type 1 fibers of muscle. Clinical improvement on oral levo-carnitine therapy suggests the possibility of carnitine deficiency as the most likely etiology in two of the patients and one had mitochondrial myopathy confirmed on genetic analysis.

  5. Possible mechanism for species difference on the toxicity of pivalic acid between dogs and rats

    International Nuclear Information System (INIS)

    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

  6. Domain Modeling: NP_003994.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_003994.2 chr9 Structural and Mutational Characterization of L-carnitine Binding ...to Human carnitine Acetyltransferase c1s5oa_ chr9/NP_003994.2/NP_003994.2_holo_9-599.pdb blast 81W,86Y,99P,320Y,322H,326E,431Y,433S,444T,497R,531S,532T,533S,545F,548V 322H 152 0 ...

  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. PMID:20691590

  8. 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.

  9. Control of lipid oxidation during exercise: role of energy state and mitochondrial factors

    DEFF Research Database (Denmark)

    Sahlin, K; Harris, R C

    2008-01-01

    Despite considerable progress during recent years our understanding of how lipid oxidation (LOx) is controlled during exercise remains incomplete. This review focuses on the role of mitochondria and energy state in the control of LOx. LOx increases in parallel with increased energy demand up...... and CHO oxidation and relative fuel utilization is mainly controlled by substrate availability and the capacity of the metabolic pathways. In the high-intensity domain (>60%VO(2max)) there is a pronounced decrease in energy state, which will stimulate glycolysis in excess of the substrate requirements...... of the oxidative processes. This will lead to acidosis, reduced levels of free Coenzyme A (CoASH) and reduced levels of free carnitine. Acidosis and reduced carnitine may limit the carnitine-mediated transfer of long-chain fatty acids (LCFA) into mitochondria and may thus explain the observed reduction in LOx...

  10. Effects of the dietary supplementation with fructooligosaccharides on the excretion of nitrogen and phosphorus in Miichthys miiuy fries

    Institute of Scientific and Technical Information of China (English)

    WU Tian-xing; SONG Zeng-fu; CAI Li-sheng; DING Xue-yan; YU Qing-sen

    2005-01-01

    Effects of dietary supplementation with fructooligosaccharides on the excretion of nitrogen and phosphorus in Miichthys miiuy fries were investigated. Nine hundred Miichthys miiuy fries were divided into 3 groups, each with triplicates. The basal diet and the basal diet supplemented with carnitine groups were considered as the negative and positive controls respectively.Results showed that the nitrogen concentration in excreted feces decreased significantly in fries fed the diet supplementation with 1000× 10-6 fructooligosaccharides and 200×10-6 carnitine (P<0.05). The ammonic-nitrogen concentration decreased significantly in the carnitine group only (P<0.05), indicating the decreasing tendency caused by the supplementation with fructooligosaccharides. Supplementation with both did not have significant effects on the concentration of phosphorus in feces ofMiichthys miiuy fries.

  11. 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......) significantly increased beta-oxidation of EPA in HPCs, but only marginally elevated the oxidation of AA in HPCs and the oxidation of both fatty acids in KCs; 2) decreased the esterification, but did not alter the preferential incorporation of AA into glycerolipids; and 3) alleviated the significant competitive...... 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...

  12. Regulation and limitations to fatty acid oxidation during exercise

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Kiens, Bente

    2012-01-01

    in turn is trapped by carnitine. This will lead to less availability of free carnitine for fatty acid transport into mitochondria. This review summarizes our present view on how FA metabolism is regulated during exercise with a special focus on the limitations in FA oxidation in the transition from...... rate of energy expenditure during high intensity exercise the total fatty acid oxidation is suppressed to below that observed during moderate intensity exercise. Although this has been known for many years, the mechanisms behind this phenomenon are still not fully elucidated. A failure of adipose...

  13. [The influence of panthotenic acid mitochondrial oxidation and oxidative phosphorylation in liver of rats with alimentary obesity].

    Science.gov (United States)

    Naruta, E E; Egorov, A I; Omel'ianchik, C N; Buko, V U

    2004-01-01

    Alimentary obesity induced by the long-term feeding of rats by high-fat diet results the reducing of rate and efficiency of oxidative phosphorylation in liver mitochondria when NAD-dependent substrates are used. The treatment of the obese rats with panthotenic acid derivatives (phosphopantotenate, panthetin, panthenol) enhanced oxidative phosphorylation of pyruvate and fatty acid carnitine esters. Among investigated compounds panthenol activated respiratory control and phosphorylation rate more effectively. Moreover, panthenol, but not phosphopanthotenate nor panthetine, increased the activity of carnitine palmitoyltransferase 1 that confirms the preferable usage of fatty acids for mitochondrial oxidation under the influence of this compound. PMID:15460980

  14. Dietary canitine maintains energy reserves and delays fatigue of exercised african catfish (Clarias gariepinus) fed high fat diets

    OpenAIRE

    Ozório Rodrigo; Van Ginneken Vincent; van den Thillart Guido; Verstegen Martin; Verreth Johan

    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 isonitrogenous diets containing a fat level of 100 or 190 g kg-1 diet and one of the two levels of carnitine (15 and 1000 mg kg-1). Fish grew from 61 to 162 g in 10 wk. Thereafter, 6 fish per group swam v...

  15. 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......-chain and carnitine transporter deficiencies. Eye examination is done in all, and liver ultrasonography in some patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase/tri-functional protein (LCHAD/TFP) deficiencies. Biochemical follow-up includes determination of free carnitine and acylcarnitines. Free...

  16. Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

    Science.gov (United States)

    2016-04-05

    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. AcEST: DK944909 [AcEST

    Lifescience Database Archive (English)

    Full Text Available +NN G Sbjct: 361 KNNPG 365 >sp|Q1RGG0|CAIB_ECOUT Crotonobetainyl-CoA:carnitine CoA-transferase OS=Escherichi...6:K15:H31 (strain 536 / UPEC) GN=caiB PE=3 SV=1 Length = 405 Score = 32.0 bits (7...jct: 361 KNNPG 365 >sp|Q0TLV1|CAIB_ECOL5 Crotonobetainyl-CoA:carnitine CoA-transferase OS=Escherichia coli O...a coli (strain UTI89 / UPEC) GN=caiB PE=3 SV=1 Length = 405 Score = 32.0 bits (71

  18. Estimation of genetic parameters and detection of quantitative trait loci for metabolites in Danish Holstein milk

    DEFF Research Database (Denmark)

    Buitenhuis, Albert Johannes; Sundekilde, Ulrik; Poulsen, Nina Aagaard;

    2013-01-01

    for lactic acid to >0.8 for orotic acid and β-hydroxybutyrate. A single SNP association analysis revealed 7 genome-wide significant quantitative trait loci [malonate: Bos taurus autosome (BTA)2 and BTA7; galactose-1-phosphate: BTA2; cis-aconitate: BTA11; urea: BTA12; carnitine: BTA25...

  19. Toxicological investigation of di(isononyl]phthalate in rats

    NARCIS (Netherlands)

    Jansen EHJM; van den Ham WA; de Fluiter P; van Leeuwen FXR

    1992-01-01

    In a study in which male rats have been exposed to 0,20, 60, 200, 600 and 2000 mg di(isononyl)phthalate (DINP)/kg diet for 2 weeks, body weight and liver weight and a number of enzyme parameters (palmitoyl coenzyme-A oxidase (PCO), enoyl coenzyme-A hydratase (ECH), carnitine acetyl transferase (CAT)

  20. Disease: H01279 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ions in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res 60:315-20 (2006) ... ...ers RJ, Ruiter JP, Keppen LD, Stein Q, Knudsen I, Gregersen N, Andresen BS Variat

  1. Non-targeted metabolomics and lipidomics LC-MS data from maternal plasma of 180 healthy pregnant women

    DEFF Research Database (Denmark)

    Luan, Hemi; Meng, Nan; Liu, Ping;

    2015-01-01

    Background: Metabolomics has the potential to be a powerful and sensitive approach for investigating the low molecular weight metabolite profiles present in maternal fluids and their role in pregnancy.Findings: In this Data Note, LC-MS metabolome, lipidome and carnitine profiling data were collec...

  2. 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....

  3. Molecular basis of transport and regulation in the Na+/betaine symporter BetP

    NARCIS (Netherlands)

    Ressl, Susanne; Terwisscha van Scheltinga, Anke C.; Vonrhein, Clemens; Ott, Vera; Ziegler, Christine

    2009-01-01

    Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by accumulation of osmolytes to restore normal hydration levels. Here we report the determination of the X-ray structure of a member of the family of betaine/choline/carnitine transporters, the Na+-cou

  4. Metabolomic study of plasma from female mink (Neovison vison) with low and high residual feed intake during restrictive and ad libitum feeding

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Damgaard, Birthe Marie

    2012-01-01

    was high during restrictive feeding, e.g. betaine, carnitine, and creatine. During ad libitum feeding the plasma level of metabolites that can be characterized as biomarkers of meat intake (creatinine, carnosine, 1- and 3 methylhistidine) was high. The plasma level of lysophosphatidylcholine species...

  5. Plasma metabolomic profiles and immune responses of piglets after weaning and challenge with E. coli

    DEFF Research Database (Denmark)

    Sugiharto, Sugiharto; Hedemann, Mette Skou; Lauridsen, Charlotte

    2014-01-01

    postweaning was observed with a principal components analysis (PCA) scores plot, and the data for day 11 were located between those for day 0 and day 4 postweaning. The plasma levels of proline, taurine, and carnitine were higher, whereas those of betaine, creatine, L-arginine and acetylcarnitine were lower...

  6. Metabolomic Analysis of Clinical Plasma from Cerebral Infarction Patients Presenting with Blood Stasis

    Directory of Open Access Journals (Sweden)

    Min Ho Cha

    2015-01-01

    Full Text Available Blood stasis (BS is characterized as a disorder of blood circulation. In traditional Korean medicine (TKM, it is viewed as a cause factor of diseases such as multiple sclerosis and stroke. This study investigated differences in the plasma metabolites profiles of subjects displaying BS or non-BS patterns. Thirty-one patients with cerebral infarction diagnosed with BS and an equal number of sex- and age-matched non-BS patients were enrolled. Metabolic profiling was performed using UPLC-MS. The ratio of subjects with a rough pulse and purple coloration of the tongue was higher in patients presenting with BS pattern. Through metabolomics analysis, 82 metabolites that differed significantly between the BS and non-BS pattern were identified, and the two groups were significantly separated using an orthogonal partial least square-discriminant analysis model (P<0.001. Of these 82 metabolites, acetyl carnitine, leucine, kynurenine, phosphocholine, hexanoyl carnitine, and decanoyl carnitine were present in significantly higher levels in patients with a BS pattern than those with a non-BS pattern. Our results also demonstrated that seven plasma metabolites, including acyl-carnitines and kynurenine, were associated with a BS pattern, suggesting that variant plasma metabolic profiles may serve as a biomarker for diagnosis of BS in patients with cerebral infarction.

  7. Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity

    DEFF Research Database (Denmark)

    Ratner, Cecilia; Madsen, Andreas Nygaard; Kristensen, Line Vildbrad;

    2015-01-01

    to ghrelin's orexigenic effects as well as ghrelin-induced attenuation of activity and energy expenditure. Thus, increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, while ghrelin...

  8. Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism

    Science.gov (United States)

    2016-09-12

    Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency; Carnitine Palmitoyltransferase Deficiencies (CPT1, CPT2); Mitochondrial Trifunctional Protein Deficiency; Long-chain Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogen Storage Disorders; Pyruvate Carboxylase Deficiency Disease; ACYL-CoA DEHYDROGENASE FAMILY, MEMBER 9, DEFICIENCY of; Barth Syndrome

  9. High-fat feeding inhibits exercise-induced increase in mitochondrial respiratory flux in skeletal muscle

    DEFF Research Database (Denmark)

    Skovbro, Mette; Boushel, Robert Christopher; Hansen, Christina Neigaard;

    2011-01-01

    .05) in state 3 (glycolytic substrates) and uncoupled respiration, respectively. However, in HFD this increase was abolished. At recovery, no change from resting respiration was seen in either group. With a lipid substrate (octanoyl-carnitine with or without ADP), similar exercise-induced increases (31...

  10. AcEST: BP913771 [AcEST

    Lifescience Database Archive (English)

    Full Text Available crotonobetaine/carnitine-CoA ligase OS=Escherichia coli (strain UTI89 / UPEC) GN=caiC PE=3 SV=2 Length = 51...a coli O6:K15:H31 (strain 536 / UPEC) GN=caiC PE=3 SV=2 Length = 517 Score = 30.0 bits (66), Expect = 9.4 Id

  11. 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

  12. Dietary Supplement Fact Sheets

    Science.gov (United States)

    ... see Thiamin ) Vitamin B12 Vitamin B2 (see Riboflavin ) Vitamin B6 C Caffeine (see Weight Loss ) Calcium Carnitine Cartilage ( ... see Thiamin ) Vitamin B12 Vitamin B2 (see Riboflavin ) Vitamin B6 Vitamin C Vitamin D Vitamin E Vitamin K ...

  13. 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...

  14. An LC-MS/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues.

    Science.gov (United States)

    Giesbertz, Pieter; Ecker, Josef; Haag, Alexander; Spanier, Britta; Daniel, Hannelore

    2015-10-01

    Acylcarnitines are intermediates of fatty acid and amino acid oxidation found in tissues and body fluids. They are important diagnostic markers for inherited diseases of peroxisomal and mitochondrial oxidation processes and were recently described as biomarkers of complex diseases like the metabolic syndrome. Quantification of acylcarnitine species can become challenging because various species occur as isomers and/or have very low concentrations. Here we describe a new LC-MS/MS method for quantification of 56 acylcarnitine species with acyl-chain lengths from C2 to C18. Our method includes amino acid-derived positional isomers, like methacrylyl-carnitine (2-M-C3:1-CN) and crotonyl-carnitine (C4:1-CN), and odd-numbered carbon species, like pentadecanoyl-carnitine (C15:0-CN) and heptadecanoyl-carnitine (C17:0-CN), occurring at very low concentrations in plasma and tissues. Method validation in plasma and liver samples showed high sensitivity and excellent accuracy and precision. In an application to samples from streptozotocin-treated diabetic mice, we identified significantly increased concentrations of acylcarnitines derived from branched-chain amino acid degradation and of odd-numbered straight-chain species, recently proposed as potential biomarkers for the metabolic syndrome. In conclusion, the LC-MS/MS method presented here allows robust quantification of isomeric acylcarnitine species and extends the palette of acylcarnitines with diagnostic potential derived from fatty acid and amino acid metabolism. PMID:26239049

  15. Trimetilaminuria: el síndrome de olor a pescado

    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 a

  16. Legal pre-event nutritional supplements to assist energy metabolism.

    Science.gov (United States)

    Spriet, Lawrence L; Perry, Christopher G R; Talanian, Jason L

    2008-01-01

    Physical training and proper nutrition are paramount for success in sport. A key tissue is skeletal muscle, as the metabolic pathways that produce energy or ATP allow the muscles to complete the many activities critical to success in sport. The energy-producing pathways must rapidly respond to the need for ATP during sport and produce energy at a faster rate or for a longer duration through training and proper nutrition which should translate into improved performance in sport activities. There is also continual interest in the possibility that nutritional supplements could further improve muscle metabolism and the provision of energy during sport. Most legal sports supplements do not improve performance following oral ingestion. However, three legal supplements that have received significant attention over the years include creatine, carnitine and sodium bicarbonate. The ingestion of large amounts of creatine for 4-6 days increases skeletal muscle creatine and phosphocreatine contents. The majority of the experimental evidence suggests that creatine supplementation can improve short-term exercise performance, especially in sports that require repeated short-term sprints. It may also augment the accretion of skeletal muscle when taken in combination with a resistance-exercise training programme. Supplementary carnitine has been touted to increase the uptake and oxidation of fat in the mitochondria. However, muscle carnitine levels are not augmented following oral carnitine supplementation and the majority of well-controlled studies have reported no effect of carnitine on enhancing fat oxidation, Vo(2max) or prolonged endurance exercise performance. The ingestion of sodium bicarbonate before intense exercise decreases the blood [H+] to potentially assist the efflux of H+ from the muscle and temper the metabolic acidosis associated with intense exercise. Many studies have reported performance increases in laboratory-based cycling tests and simulated running races in

  17. Lipid storage myopathy with clinical markers of Marfan syndrome: A rare association

    Directory of Open Access Journals (Sweden)

    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.

  18. Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

    Science.gov (United States)

    Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

    2016-08-01

    A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. PMID:27324861

  19. Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation.

    OpenAIRE

    Corr, P B; Creer, M H; Yamada, K.A.; Saffitz, J E; Sobel, B. E.

    1989-01-01

    Hypoxia in isolated myocytes results in accumulation of long-chain acylcarnitines (LCA) in sarcolemma. Inhibition of carnitine acyltransferase I (CAT-I) with sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) prevents both the accumulation of LCA in the sarcolemma and the initial electrophysiologic derangements associated with hypoxia. Another amphiphilic metabolite, lysophosphatidylcholine (LPC), accumulates in the ischemic heart in vivo, in part because of inhibition of its c...

  20. Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

    OpenAIRE

    Paris Jafari; Olivier Braissant; Petra Zavadakova; Hugues Henry; Luisa Bonafé; Diana Ballhausen

    2013-01-01

    Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated...

  1. Specific Osmolyte Transporters Mediate Bile Tolerance in Listeria monocytogenes▿

    OpenAIRE

    Watson, Debbie; Sleator, Roy D.; Casey, Pat G.; Hill, Colin; Gahan, Cormac G. M.

    2009-01-01

    The food-borne pathogenic bacterium Listeria monocytogenes has the potential to adapt to an array of suboptimal growth environments encountered within the host. The pathogen is relatively bile tolerant and has the capacity to survive and grow within both the small intestine and the gallbladder in murine models of oral infection. We have previously demonstrated a role for the principal carnitine transport system of L. monocytogenes (OpuC) in gastrointestinal survival of the pathogen (R. Sleato...

  2. Complex III deficiency due to an in-frame MT-CYB deletion presenting as ketotic hypoglycemia and lactic acidosis

    Directory of Open Access Journals (Sweden)

    Mari Mori

    2015-09-01

    Full Text Available Complex III deficiency due to a MT-CYB mutation has been reported in patients with myopathy. Here, we describe a 15-year-old boy who presented with metabolic acidosis, ketotic hypoglycemia and carnitine deficiency. Electron transport chain analysis and mitochondrial DNA sequencing on muscle tissue lead to the eventual diagnosis of complex III deficiency. This case demonstrates the critical role of muscle biopsies in a myopathy work-up, and the clinical efficacy of supplement therapy.

  3. 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

    -acetylcarnitine, 2-metylbutyroylcarnitine), glycerophosphocholine, and betaine. l-Acetylcarnitine and 2-metylbutyroylcarnitine, involved in the metabolism and transport of fatty acids, decreased in milk compared to colostrum, whereas l-carnitine presented an opposite trend (P ..., glycerophosphocholine and choline decreased from colostrum to milk, whereas betaine showed higher values in milk compared to colostrum. The use of liquid chromatography–mass spectrometry metabolomics as a hypothesis generator tool opens up new questions with regard to the origin and function of mammary gland...

  4. Sites of superoxide and hydrogen peroxide production during fatty acid oxidation in rat skeletal muscle mitochondria

    OpenAIRE

    Perevoshchikova, Irina V.; Quinlan, Casey L.; Orr, Adam L.; Gerencser, Akos A.; Brand, Martin D.

    2013-01-01

    H2O2 production by skeletal muscle mitochondria oxidizing palmitoylcarnitine was examined under two conditions: the absence of respiratory chain inhibitors and the presence of myxothiazol to inhibit complex III. Without inhibitors, respiration and H2O2 production were low unless carnitine or malate was added to limit acetyl-CoA accumulation. With palmitoylcarnitine alone, H2O2 production was dominated by complex II (44% from site IIF in the forward reaction); the remainder was mostly from com...

  5. Knock, knock, knocking on muscle doors. Visions on the transport of substrates across the plasma membrane in muscle.

    OpenAIRE

    Zorzano Olarte, Antonio; Fandos Espallargas, César; Palacín Prieto, Manuel

    2001-01-01

    Muscle is a major player in metabolism. It uses large amounts of glucose in the absorptive state and changes in muscle insulin-stimulated glucose uptake alter whole-body glucose disposal. Lipid substrates such as fatty acids or ketone bodies are preferentially used by muscle in certain physiological conditions. Muscle is also the main reservoir of amino acids and protein. The activity of many different plasma membrane transporters such as glucose carriers, carnitine, creatine or amino acid tr...

  6. Roles and Regulation of Ketogenesis in Cultured Astroglia and Neurons Under Hypoxia and Hypoglycemia

    OpenAIRE

    Takahashi, Shinichi; Iizumi, Takuya; Mashima, Kyoko; Abe, Takato; Suzuki, Norihiro

    2014-01-01

    Exogenous ketone bodies (KBs), acetoacetate (AA), and β-hydroxybutyrate (BHB) act as alternative energy substrates in neural cells under starvation. The present study examined the endogenous ketogenic capacity of astroglia under hypoxia with/without glucose and the possible roles of KBs in neuronal energy metabolism. Cultured neurons and astroglia were prepared from Sprague-Dawley rats. Palmitic acid (PAL) and l-carnitine (LC) were added to the assay medium. The 4- to 24-hr production of AA a...

  7. Comparison of pre-workout nitric oxide stimulating dietary supplements on skeletal muscle oxygen saturation, blood nitrate/nitrite, lipid peroxidation, and upper body exercise performance in resistance trained men

    OpenAIRE

    Canale Robert E; McCarthy Cameron G; Trepanowski John F; Farney Tyler M; Bloomer Richard J; Schilling Brian K

    2010-01-01

    Abstract Background We compared Glycine Propionyl-L-Carnitine (GlycoCarn®) and three different pre-workout nutritional supplements on measures of skeletal muscle oxygen saturation (StO2), blood nitrate/nitrite (NOx), lactate (HLa), malondialdehyde (MDA), and exercise performance in men. Methods Using a randomized, double-blind, cross-over design, 19 resistance trained men performed tests of muscular power (bench press throws) and endurance (10 sets of bench press to muscular failure). A place...

  8. Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging

    OpenAIRE

    Janson, Michael

    2006-01-01

    Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quer...

  9. Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy.

    Directory of Open Access Journals (Sweden)

    Karen L Lindsay

    Full Text Available Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as

  10. The Natural Antioxidants, Pomegranate Extract and Soy Isoflavones, Favourably Modulate Canine Endothelial Cell Function

    OpenAIRE

    Baumgartner-Parzer, Sabina M; Ferdinand Rudolf Waldenberger; Angelika Freudenthaler; Amandine Ginouvès-Guerdoux; David McGahie; Hugues Gatto

    2012-01-01

    Cardiovascular disease, preceded by vascular endothelial dysfunction, is a prominent cause of death in dogs. L-carnitine and taurine, well known for their antioxidative capacity, beneficially affect cardiovascular disease as well as certain dog cardiomyopathies. It is well established that vascular endothelial dysfunction precedes cardiovascular disease and that “vasoprotective factors” (NO and antioxidants) prevent apoptosis, whereas “risk factors” such as oxidized LDL, hyperglycemia, and fr...

  11. Identification of Factors Associated With Sural Nerve Regeneration and Degeneration in Diabetic Neuropathy

    OpenAIRE

    Hur, Junguk; Sullivan, Kelli A; Callaghan, Brian C.; Pop-Busui, Rodica; Eva L Feldman

    2013-01-01

    OBJECTIVE Patients with diabetic neuropathy (DN) demonstrate variable degrees of nerve regeneration and degeneration. Our aim was to identify risk factors associated with sural nerve degeneration in patients with DN. RESEARCH DESIGN AND METHODS Demographic, anthropometric, biochemical, and anatomical data of subjects with DN from a 52-week trial of acetyl- L -carnitine were retrospectively examined. Based on the change in sural nerve myelinated fiber density (ΔMFD%), subjects were divided int...

  12. Vitamin C in human health and disease is still a mystery ? An overview

    OpenAIRE

    Naidu K Akhilender

    2003-01-01

    Abstract Ascorbic acid is one of the important water soluble vitamins. It is essential for collagen, carnitine and neurotransmitters biosynthesis. Most plants and animals synthesize ascorbic acid for their own requirement. However, apes and humans can not synthesize ascorbic acid due to lack of an enzyme gulonolactone oxidase. Hence, ascorbic acid has to be supplemented mainly through fruits, vegetables and tablets. The current US recommended daily allowance (RDA) for ascorbic acid ranges bet...

  13. Preventive effects of metallothionein against DNA and lipid metabolic damages in dyslipidemic mice under repeated mild stress

    OpenAIRE

    Higashimoto, Minoru; Isoyama, Naohiro; Ishibashi, Satoshi; Ogawa, Naoko; Takiguchi, Masufumi; Suzuki, Shinya; Ohnishi, Yoshinari; Sato, Masao

    2013-01-01

    The effects of repeated mild stress on DNA and lipid metabolic damages in multiple organs of dyslipidemic mice, and the preventive role of metallothionein (MT) were investigated. Female adult wild-type and MT-null mice fed high-fat diet (HFD) or standard diet (STD) were repeatedly subjected to fasting or restraint for three weeks. The liver, pancreas, spleen, bone marrow and serum samples were taken for evaluating DNA damage, MT, glutathione (GSH), corticosterone, carnitine and adiponectin. B...

  14. The natural antioxidants, pomegranate extract and soy isoflavones, favourably modulate canine endothelial cell function.

    Science.gov (United States)

    Baumgartner-Parzer, Sabina M; Waldenberger, Ferdinand Rudolf; Freudenthaler, Angelika; Ginouvès-Guerdoux, Amandine; McGahie, David; Gatto, Hugues

    2012-01-01

    Cardiovascular disease, preceded by vascular endothelial dysfunction, is a prominent cause of death in dogs. L-carnitine and taurine, well known for their antioxidative capacity, beneficially affect cardiovascular disease as well as certain dog cardiomyopathies. It is well established that vascular endothelial dysfunction precedes cardiovascular disease and that "vasoprotective factors" (NO and antioxidants) prevent apoptosis, whereas "risk factors" such as oxidized LDL, hyperglycemia, and free fatty acids trigger it in cultured human vascular endothelial cells. Whereas human vascular cell in vitro models are widely established and used for the characterisation of potential vasoprotective substances, such models are not available for canine endothelial cells. In the present study we therefore developed an in vitro model, which allows the testing of the effects of different substances on proliferation and apoptosis in canine aortic endothelial cells. This model was used to test L-carnitine, taurine, pomegranate extract, and Soy Isoflavones in comparison to reference substances (glutathione and pioglitazone) previously shown to modulate human endothelial cell function. L-carnitine and taurine neither exhibited antiproliferative nor antiapoptotic activities in the context of this study. However extracts from pomegranate and soy isoflavones dramatically reduced proliferation and apoptosis in a dose dependent fashion, being in line with a vasoprotective activity in dogs.

  15. The natural antioxidants, pomegranate extract and soy isoflavones, favourably modulate canine endothelial cell function.

    Science.gov (United States)

    Baumgartner-Parzer, Sabina M; Waldenberger, Ferdinand Rudolf; Freudenthaler, Angelika; Ginouvès-Guerdoux, Amandine; McGahie, David; Gatto, Hugues

    2012-01-01

    Cardiovascular disease, preceded by vascular endothelial dysfunction, is a prominent cause of death in dogs. L-carnitine and taurine, well known for their antioxidative capacity, beneficially affect cardiovascular disease as well as certain dog cardiomyopathies. It is well established that vascular endothelial dysfunction precedes cardiovascular disease and that "vasoprotective factors" (NO and antioxidants) prevent apoptosis, whereas "risk factors" such as oxidized LDL, hyperglycemia, and free fatty acids trigger it in cultured human vascular endothelial cells. Whereas human vascular cell in vitro models are widely established and used for the characterisation of potential vasoprotective substances, such models are not available for canine endothelial cells. In the present study we therefore developed an in vitro model, which allows the testing of the effects of different substances on proliferation and apoptosis in canine aortic endothelial cells. This model was used to test L-carnitine, taurine, pomegranate extract, and Soy Isoflavones in comparison to reference substances (glutathione and pioglitazone) previously shown to modulate human endothelial cell function. L-carnitine and taurine neither exhibited antiproliferative nor antiapoptotic activities in the context of this study. However extracts from pomegranate and soy isoflavones dramatically reduced proliferation and apoptosis in a dose dependent fashion, being in line with a vasoprotective activity in dogs. PMID:23762588

  16. Energy metabolic disorder is a major risk factor in severe influenza virus infection: Proposals for new therapeutic options based on animal model experiments.

    Science.gov (United States)

    Kido, Hiroshi; Indalao, Irene L; Kim, Hyejin; Kimoto, Takashi; Sakai, Satoko; Takahashi, Etsuhisa

    2016-09-01

    Severe influenza is characterized by cytokine storm and multiorgan failure. Influenza patients with underlying diseases show a rapid progression in disease severity. The major mechanism that underlies multiorgan failure during the progressive stage of infection, particularly in patients with underlying risk factors, is mitochondrial energy crisis. The relationship between the factors that determine infection severity, such as influenza virus, cytokines, cellular trypsin as a hemagglutinin processing protease for viral multiplication, accumulation of metabolic intermediates and ATP crisis in mitochondria, is termed the "influenza virus-cytokine-trypsin" cycle. This occurs during the initial stages of infection, and is interconnected with the "metabolic disorders-cytokine" cycle in the middle to late phase of infection. Experiments using animal models have highlighted the complex relationship between these two cycles. New treatment options have been proposed that target the ATP crisis and multiorgan failure during the late phase of infection, rather than antiviral treatments with neuraminidase inhibitors that work during the initial phase. These options are (i) restoration of glucose oxidation in mitochondria by diisopropylamine dichloroacetate, which inhibits infection-induced pyruvate dehydrogenase kinase 4 activity, and (ii) restoration of long-chain fatty acid oxidation in mitochondria by l-carnitine and bezafibrate, an agonist of peroxisome proliferation-activated receptors-β/δ, which transcriptionally upregulates carnitine palmitoyltransferase II. The latter is particularly effective in patients with influenza-associated encephalopathy who have thermolabile and short half-life compound variants of carnitine palmitoyltransferase II. PMID:27566378

  17. Natural products and complementary therapies for chemotherapy-induced peripheral neuropathy: A systematic review.

    Science.gov (United States)

    Brami, Cloé; Bao, Ting; Deng, Gary

    2016-02-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl-L-carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. L-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-L-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions. PMID:26652982

  18. Obesity and Subsequent Cardiovascular Events in Rats and The Potential Benefits of some Antioxidants Supplementation

    International Nuclear Information System (INIS)

    This study focuses on the relationship between the obesity and cardiovascular diseases (CVD) and the possible amelioration effects of curcumin or L-carnitine and their mixture on cardiac and lipid profiles tests. Obesity is associated with abnormal endothelial function and it is often inferred that the reduction in endothelial function is the result of a decrease in nitric oxide (NO). Moreover, asymmetric dimethyl arginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOs) activity. This modified amino acid is derived from proteins that have been post-translationally methylated and subsequently hydrolyzed. In the current study, obesity was induced in the rats by receiving orally 200 mg cholesterol/100 g by the aid of gastric tube together with injection i.m. 30 mg cholic acid/100 g for one month. After one month of induction of hyper-cholesterolemia in rats and in comparison to normal rats, the results showed that incorporation of extra cholesterol in diet led to a significant increase in serum cholesterol, triglycerides, LDL, HDL, VLDL-cholesterol and resistin levels. Moreover, significant elevations in the levels of AST, LDH, CK, ADMA and endotheline-1 were recorded in obese rats compared with normal rats. All previous parameters were corrected after the hypercholesterolemic rats were treated with curcumin or L-carnitine and their mixture depending on the time of treatment. These findings are consistent with the concept that curcumin and L-carnitine are hypolipidemic agents and powerful antioxidants

  19. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice.

    Science.gov (United States)

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-01-01

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. (13)C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise. PMID:26916151

  20. Diagnosis and treatment of congestive heart failure secondary to dilated cardiomyopathy in a hedgehog.

    Science.gov (United States)

    Delk, K W; Eshar, D; Garcia, E; Harkin, K

    2014-03-01

    A one-year-old African pygmy hedgehog (Atelerix albiventris) was evaluated for severe respiratory distress. Physical examination findings included marked dyspnoea, cyanosis and tachypnoea. Radiographic findings included an enlarged heart and pulmonary oedema, and dilated cardiomyopathy was confirmed via echocardiogram. The patient was treated for congestive heart failure because of dilated cardiomyopathy with furosemide, enalapril, pimobendan and l-carnitine. Within 24 hours of treatment, the pulmonary oedema and cyanosis had resolved. Following discharge, clinical improvement was noted by the owner and echocardiogram confirmed improved fractional shortening. Cardiomyopathy has been reported at post-mortem examination in hedgehogs, but there are no reports of ante-mortem diagnosis and treatment. Performing baseline cardiac assessment in hedgehogs is recommended, and treatment with l-carnitine and pimobendan may improve outcome, as carnitine deficiency is a possible cause of cardiomyopathy in hedgehogs. Successful emergency treatment of congestive heart failure in the hedgehog of this report may be effective for other hedgehogs presented with similar clinical signs. PMID:24372164

  1. Alternative reactions at the interface of glycolysis and citric acid cycle in Saccharomyces cerevisiae.

    Science.gov (United States)

    van Rossum, Harmen M; Kozak, Barbara U; Niemeijer, Matthijs S; Duine, Hendrik J; Luttik, Marijke A H; Boer, Viktor M; Kötter, Peter; Daran, Jean-Marc G; van Maris, Antonius J A; Pronk, Jack T

    2016-05-01

    Pyruvate and acetyl-coenzyme A, located at the interface between glycolysis and TCA cycle, are important intermediates in yeast metabolism and key precursors for industrially relevant products. Rational engineering of their supply requires knowledge of compensatory reactions that replace predominant pathways when these are inactivated. This study investigates effects of individual and combined mutations that inactivate the mitochondrial pyruvate-dehydrogenase (PDH) complex, extramitochondrial citrate synthase (Cit2) and mitochondrial CoA-transferase (Ach1) in Saccharomyces cerevisiae. Additionally, strains with a constitutively expressed carnitine shuttle were constructed and analyzed. A predominant role of the PDH complex in linking glycolysis and TCA cycle in glucose-grown batch cultures could be functionally replaced by the combined activity of the cytosolic PDH bypass and Cit2. Strongly impaired growth and a high incidence of respiratory deficiency in pda1Δ ach1Δ strains showed that synthesis of intramitochondrial acetyl-CoA as a metabolic precursor requires activity of either the PDH complex or Ach1. Constitutive overexpression of AGP2, HNM1, YAT2, YAT1, CRC1 and CAT2 enabled the carnitine shuttle to efficiently link glycolysis and TCA cycle in l-carnitine-supplemented, glucose-grown batch cultures. Strains in which all known reactions at the glycolysis-TCA cycle interface were inactivated still grew slowly on glucose, indicating additional flexibility at this key metabolic junction.

  2. The mechanism of dietary cholesterol effects on lipids metabolism in rats

    Directory of Open Access Journals (Sweden)

    Wang Jing-Feng

    2010-01-01

    Full Text Available Abstract Background Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively. The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds in liver by the cholesterol administration. Conclusions The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.

  3. Dietary canitine maintains energy reserves and delays fatigue of exercised african catfish (Clarias gariepinus fed high fat diets Carnitina dietética mantem reservas energéticas e evita a fatiga de bagre-africano durante exercício

    Directory of Open Access Journals (Sweden)

    Rodrigo Ozório

    2005-06-01

    Full Text Available 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 isonitrogenous diets containing a fat level of 100 or 190 g kg-1 diet and one of the two levels of carnitine (15 and 1000 mg kg-1. Fish grew from 61 to 162 g in 10 wk. Thereafter, 6 fish per group swam vigorously for 3 h and the results were compared with unexercised groups. Fish receiving 1,000 mg carnitine accumulated 2- to 3-fold more carnitine than fish receiving 15 mg carnitine. Plasma acyl-carnitine level was affected by an interaction between dietary treatment and exercise (P Lipídios e proteínas são tradicionalmente considerados combustíveis primários durante natação aeróbica. Nesse ensaio foi investigado o efeito da suplementação de vários níveis de gordura e carnitina no metabolismo de 100 bagres africanos juvenis (Clarias gariepinus. Os peixes foram arraçoados com quatro dietas isoprotéicas, cada uma contendo 100 ou 190 g gordura kg-1 dieta, e um dos dois níveis de carnitina (15 e 1000 mg kg-1. Os peixes cresceram de 61 a 162 g em 10 semanas. No final do ensaio de alimentação, grupos de seis peixes por tratamento foram induzidos a nadar vigorosamente por 3 h e em seguida vários parâmetros foram determinados no tecido muscular e plasma, e os resultados observados nos grupos exercitados foram comparados com grupos controles (não exercitados. Os peixes arraçoados com 1,000 mg carnitina acumularam de duas a três vezes mais carnitina que os peixes arraçoados com 15 mg carnitina. O nível de acyl-carnitina no plasma foi influenciado pela interação entre os tratamentos dietéticos e exercício físico (P < 0.05. As concentrações de adenosina trifosfato (ATP e fosfocreatina no tecido muscular branco (WM foram mais elevadas em

  4. Customized nutritional enhancement for pregnant women appears to lower incidence of certain common maternal and neonatal complications: an observational study.

    Science.gov (United States)

    Stone, Leslie P; Stone, P Michael; Rydbom, Emily A; Stone, Lucas A; Stone, T Elliot; Wilkens, Lindsey E; Reynolds, Kathryn

    2014-11-01

    A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention. Intervention consisted of trimesterby-trimester nutrition and lifestyle education, supplementation of L-methyl folate, magnesium, essential fatty acids, and probiotics for all SG patients, with targeted supplementation of zinc, carnitine, and 25 OH-D. Because of small case occurrence rates of individual conditions in the study group, unreportable reductions were found, except GDM (SG vs CHCC, P value .046 with 95.38% confidence interval [CI]), and PIH (SG vs PP, P value .0505 with 94.95% CIl). The aggregated occurrence rate of the four conditions, however, was significantly lower in the study population than in either comparison population (PP P value .0154 with 98.46% CI, and CHCC P value .0265 with 97.35% CI). Customized nutritional intervention appears to have significantly reduced adverse perinatal outcomes. Prospective study within larger, at-risk populations is needed to determine whether customized nutrition improves conditions individually.

  5. Customized nutritional enhancement for pregnant women appears to lower incidence of certain common maternal and neonatal complications: an observational study.

    Science.gov (United States)

    Stone, Leslie P; Stone, P Michael; Rydbom, Emily A; Stone, Lucas A; Stone, T Elliot; Wilkens, Lindsey E; Reynolds, Kathryn

    2014-11-01

    A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention. Intervention consisted of trimesterby-trimester nutrition and lifestyle education, supplementation of L-methyl folate, magnesium, essential fatty acids, and probiotics for all SG patients, with targeted supplementation of zinc, carnitine, and 25 OH-D. Because of small case occurrence rates of individual conditions in the study group, unreportable reductions were found, except GDM (SG vs CHCC, P value .046 with 95.38% confidence interval [CI]), and PIH (SG vs PP, P value .0505 with 94.95% CIl). The aggregated occurrence rate of the four conditions, however, was significantly lower in the study population than in either comparison population (PP P value .0154 with 98.46% CI, and CHCC P value .0265 with 97.35% CI). Customized nutritional intervention appears to have significantly reduced adverse perinatal outcomes. Prospective study within larger, at-risk populations is needed to determine whether customized nutrition improves conditions individually. PMID:25568832

  6. A requirement for fatty acid oxidation in the hormone-induced meiotic maturation of mouse oocytes.

    Science.gov (United States)

    Valsangkar, Deepa; Downs, Stephen M

    2013-08-01

    We have previously shown that fatty acid oxidation (FAO) is required for AMP-activated protein kinase (PRKA)-induced maturation in vitro. In the present study, we have further investigated the role of this metabolic pathway in hormone-induced meiotic maturation. Incorporating an assay with (3)H-palmitic acid as the substrate, we first examined the effect of PRKA activators on FAO levels. There was a significant stimulation of FAO in cumulus cell-enclosed oocytes (CEO) treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and RSVA405. In denuded oocytes (DO), AICAR stimulated FAO only in the presence of carnitine, the molecule that facilitates fatty acyl CoA entry into the mitochondria. The carnitine palmitoyltransferase 1 activator C75 successfully stimulated FAO in CEO. All three of these activators trigger germinal vesicle breakdown. Meiotic resumption induced by follicle-stimulating hormone (FSH) or amphiregulin was completely inhibited by the FAO inhibitors etomoxir, mercaptoacetate, and malonyl CoA. Importantly, FAO was increased in CEO stimulated by FSH and epidermal growth factor, and this increase was blocked by FAO inhibitors. Moreover, compound C, a PRKA inhibitor, prevented the FSH-induced increase in FAO. Both carnitine and palmitic acid augmented hormonal induction of maturation. In a more physiological setting, etomoxir eliminated human chorionic gonadotropin (hCG)-induced maturation in follicle-enclosed oocytes. In addition, CEO and DO from hCG-treated mice displayed an etomoxir-sensitive increase in FAO, indicating that this pathway was stimulated during in vivo meiotic resumption. Taken together, our data indicate that hormone-induced maturation in mice requires a PRKA-dependent increase in FAO. PMID:23863407

  7. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Derrick F. MacFabe

    2012-08-01

    Full Text Available Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs. Propionic acid (PPA and its related short-chain fatty acids (SCFAs are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio. SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible

  8. Medium chain acylcarnitines dominate the metabolite pattern in humans under moderate intensity exercise and support lipid oxidation.

    Directory of Open Access Journals (Sweden)

    Rainer Lehmann

    Full Text Available BACKGROUND: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise. METHODOLOGY AND PRINCIPAL FINDINGS: First, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT- metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under these conditions medium and long chain acylcarnitines were found to be the most discriminant plasma biomarkers of moderately intense exercise. Immediately after a 60 min (at 93% V(IAT or a 120 min run (at 70% V(IAT a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial beta-oxidation was verified in skeletal muscle cell culture experiments by probing (13C-palmitate metabolism. Further investigations in primary human myotubes and mouse muscle tissue revealed that octanoyl-, decanoyl-, and dodecanoyl-carnitine were able to support the oxidation of palmitate, proving more effective than L-carnitine. CONCLUSIONS: Medium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.

  9. Male idiopathic oligoasthenoteratozoospermia

    Institute of Scientific and Technical Information of China (English)

    Giorgio Cavallini

    2006-01-01

    Idiopathic oligoasthenoteratozoospermia (iOAT) affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular organs, infective agents (Chlamydia trachomatis, herpes virus and adeno-associated viruses), alterations in gamete genome, mitochondrial alterations, environmental pollutants and "subtle" hormonal alterations are all considered possible causes of iOAT.Increase of reactive oxygen species in tubules and in seminal plasma and of apoptosis are reputed to affect sperm concentration, motility and morphology. iOAT is commonly diagnosed by exclusion, nevertheless spectral traces of the main testicular artery may be used as a diagnostic tool for iOAT. The following can be considered therapies for iOAT: 1) tamoxifen citrate (20 mg/d) + testosterone undecanoate (120 mg/d) (pregnancy rate per couple/month [prcm]:3.8%); 2) folic acid (66 mg/d) + zinc sulfate (5 mg/d); 3) L-carnitine (2 g/d) alone or in combination with acetyl-L-carnitine (1 g/d) (prcm: 2.3%); and 4) both carnitines + one 30 mg cinnoxicam suppository every 4 days (prcm: 8.5%).Alpha-blocking drugs improved sperm concentration but not morphology, motility or pregnancy rate. Tranilast (300 mg/d) increased sperm parameters and pregnancy rates in an initial uncontrolled study. Its efficacy on sperm concentration (but not on sperm motility, morphology or prcm) was confirmed in subsequent published reports. The efficacy of tamoxifen + testosterone undecanoate, tamoxifen alone, and recombinant follicle-stimulating hormone is still a matter for discussion.

  10. Metabolite profile of a mouse model of Charcot-Marie-Tooth type 2D neuropathy: implications for disease mechanisms and interventions.

    Science.gov (United States)

    Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H; Currie, Meagan E; Norberg, Sara N; Evsikov, Alexei V; Miers, Kathy E; Seburn, Kevin L; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J; Burgess, Robert W

    2016-01-01

    Charcot-Marie-Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot-Marie-Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite 'fingerprint' we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies.

  11. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation.

    Directory of Open Access Journals (Sweden)

    Li-Li Wen

    Full Text Available Perfluorinated chemicals (PFCs are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs. In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1 by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation.

  12. Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

    Science.gov (United States)

    Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H.; Currie, Meagan E.; Norberg, Sara N.; Evsikov, Alexei V.; Miers, Kathy E.; Seburn, Kevin L.; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J.

    2016-01-01

    ABSTRACT Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

  13. Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

    Directory of Open Access Journals (Sweden)

    Preeti Bais

    2016-07-01

    Full Text Available Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D is caused by dominant mutations in glycyl tRNA synthetase (GARS. Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies.

  14. Effects of amino acid derivatives on physical, mental, and physiological activities.

    Science.gov (United States)

    Luckose, Feby; Pandey, Mohan Chandra; Radhakrishna, Kolpe

    2015-01-01

    Nutritional ergogenic aids have been in use for a long time to enhance exercise and sports performance. Dietary components that exhibit ergogenic activity are numerous and their consumption is common and popular among athletes. They often come under scrutiny by legal authorities for their claimed benefits and safety concerns. Amino acid derivatives are propagated as being effective aids to enhance physical and mental performance in many ways, even though studies have pointed out that individuals who are deficient are more likely to benefit from dietary supplementation of amino acid derivatives than normal humans. In this review, some of the most common and widely used amino acids derivatives in sports and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been discussed for their effects on exercise performance, mental activity as well as body strength and composition. Creatine, carnitine, HMB, and taurine are reported to delay the onset of fatigue, improve exercise performance, and body strength. HMB helps in increasing fat-free mass and reduce exercise induced muscle injury. Taurine has been found to reduce oxidative stress during exercise and also act as an antihypertensive agent. Although, studies have not been able to find any favorable effect of tyrosine administration on exercise performance, it has been proved to be very effective in fighting stress, improving mood and cognitive performance particularly in sleep-deprived subjects. While available data from published studies and findings are equivocal about the efficacy of creatine, tyrosine, and HMB, more comprehensive researches on carnitine and taurine are necessary to provide evidence for the theoretical basis of their ergogenic role in nutritional modification and supplementation. PMID:24279396

  15. Analysis of the role of OpuC, an osmolyte transport system, in salt tolerance and virulence potential of Listeria monocytogenes

    OpenAIRE

    Sleator, R.D.; Wouters, J.; Gahan, C.G.M.; Abee, T; Hill, C.

    2001-01-01

    The success of Listeria monocytogenes as a food-borne pathogen owes much to its ability to survive a variety of stresses, both in the external environment prior to ingestion and subsequently within the animal host. Growth at high salt concentrations and low temperatures is attributed mainly to the accumulation of organic solutes such as glycine betaine and carnitine. We utilized a novel system for generating chromosomal mutations (based on a lactococcal pWVO1-derived Ori+ RepA− vector, pORI19...

  16. Transcriptional Regulation and Posttranslational Activity of the Betaine Transporter BetL in Listeria monocytogenes Are Controlled by Environmental Salinity

    OpenAIRE

    Sleator, Roy D.; Wood, Janet M.; Hill, Colin

    2003-01-01

    While the genetic elements contributing to the salinity tolerance of Listeria monocytogenes have been well characterized, the regulatory signals and responses (genetic and/or biochemical) that govern these mechanisms have yet to be elucidated. Encoded by betL, the first genetic element to be linked to listerial osmotolerance, the secondary betaine uptake system BetL is a member of the betaine-carnitine-choline transporter family. Preceded by consensus σA- and σB-dependent promoter sites, betL...

  17. Multiple deletions of the osmolyte transporters BetL, Gbu, and OpuC of Listeria monocytogenes affect virulence and growth at high osmolarity

    OpenAIRE

    Wemekamp-Kamphuis, H.H.; Wouters, J.A.; Sleator, R.D.; Gahan, C.G.M.; Hill, C.; Abee, T

    2002-01-01

    The success of Listeria monocytogenes as a food-borne pathogen owes much to its ability to survive a variety of stresses, both in the food environment and, after ingestion, within the animal host. Growth at high salt concentrations is attributed mainly to the accumulation of organic solutes such as glycine betaine and carnitine. We characterized L. monocytogenes LO28 strains with single, double, and triple deletions in the osmolyte transport systems BetL, Gbu, and OpuC. When single deletion m...

  18. Acute Pancreatitis with Rapid Clinical Improvement in a Child with Isovaleric Acidemia

    Directory of Open Access Journals (Sweden)

    Elpis Mantadakis

    2013-01-01

    Full Text Available Isovaleric acidemia is a rare branched-chain organic acidemia. The authors describe a 3.5-year-old girl with isovaleric acidemia and acute abdominal pain associated with bilious emesis. Elevated serum amylase and abdominal ultrasonography demonstrating an enlarged and edematous pancreas, along with the presence of peripancreatic exudates, confirmed the presence of acute pancreatitis. The patient recovered quickly with intravenous hydration, pancreatic rest, and administration of intravenous L-carnitine. Pancreatitis should be ruled out in the context of vomiting in any patient with isovaleric acidemia. Conversely, branched-chain organic acidemias should be included in the differential diagnosis of any child with pancreatitis of unknown origin.

  19. n-3 LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1

    OpenAIRE

    Tapia, G. S.; González-Mañán, D.; D’Espessailles, A.; Dossi, C. G.

    2016-01-01

    The aim of this study was to investigate the roles of the Acyl co-enzyme A oxidase (ACOX), carnitine acyl transferase I (CAT-1) and activating protein 1 (AP-1) in the reversal of hepatic steatosis with dietary change and n-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation. Male C57BL/6J mice were given either a control diet (CD) or a high fat diet (HFD) for 12 weeks, and then continued with the CD or CD plus n-3 LCPUFA for eight weeks. After this period, body and adipose vi...

  20. Skeletal muscle mitochondrial respiration in AMPKa2 kinase dead mice

    DEFF Research Database (Denmark)

    Larsen, Steen; Kristensen, Jonas Møller; Stride, Nis;

    2012-01-01

    AIM: To study if the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKa2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2...... a substrate-uncoupler-inhibitor-titration (SUIT) protocol: malate, octanoyl-carnitine, ADP and glutamate (GMO(3) ), +succinate (GMOS(3) ), +uncoupler (U) and inhibitor (rotenone) of complex I respiration. Citrate synthase (CS) activity was measured as and index of mitochondrial content. RESULTS: CS activity...

  1. Diagnosis and management of glutaric aciduria type I--revised recommendations

    DEFF Research Database (Denmark)

    Kölker, Stefan; Christensen, Ernst; Leonard, James V;

    2011-01-01

    precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L...... is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine...

  2. Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging.

    Science.gov (United States)

    Janson, Michael

    2006-01-01

    Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems. PMID:18046879

  3. Late-onset form of beta-electron transfer flavoprotein deficiency

    DEFF Research Database (Denmark)

    Curcoy, A; Olsen, R K J; Ribes, A;

    2003-01-01

    and biochemical and molecular genetic analyses of a patient with a mild late-onset form of GAII due to beta-ETF deficiency. Biochemical data showed an abnormal urine organic acid profile, low levels of free carnitine, increased levels of C(10:1n-6), and C(14:1n-9) in plasma, and decreased oxidation of [9,10-3H...... in the ETFB gene resulting in the deletion of lysine-202 (K202del). The present report delineates further the phenotype of mild beta-ETF deficiency and illustrates that the differential diagnosis of GAII is readily achieved by mutational analysis....

  4. Multimodal imaging-monitored progression of stroke-like episodes in a case of MELAS syndrome.

    Science.gov (United States)

    Namer, Izzie Jacques; Wolff, Valérie; Dietemann, Jean-Louis; Marescaux, Christian

    2014-03-01

    We report imaging findings during, between, and after 2 stroke-like episodes in a 45-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome with an A32243G mitochondrial mutation 6 years before. In November 2010, for a first episode, she showed mixed aphasia with logorrhea, disinhibition, agitation, euphoria, and a large left temporoparietal lesion. Symptomatology progressively regressed under L-arginine treatment. She was readmitted in June 2011 for a second episode with great anxiety, disorientation, impaired face recognition, worsening mixed aphasia, and a new right temporal lesion. After additional L-carnitine treatment, she remained without relapse for 14 months.

  5. Integrative Therapies and Cardiovascular Disease in the Breast Cancer Population: A Review, Part 1.

    Science.gov (United States)

    Lucius, Khara; Trukova, Kristen

    2015-08-01

    The cardiovascular toxicities of breast cancer treatment are important health problems, with potential public health consequences. Integrative therapies may represent important tools for prevention in this population. This article reviews the cardiotoxicity of conventional breast cancer therapy, including chemotherapy, radiation, and hormonal therapy. Data are presented on the benefits of substances such as curcumin, melatonin, Ginkgo biloba, resveratrol, coenzyme Q10, and l-carnitine. Although clinical studies on many of these substances are limited both in size and number, preclinical studies are available for several, and this article summarizes the potential mechanisms of action. Areas for future research are also identified. PMID:26770154

  6. Nutritional considerations for the dialytic patient.

    Science.gov (United States)

    Elliott, Denise A

    2011-01-01

    Nutritional therapy has a key role in the conservative management of renal disease. This role is even more vital with the advent of advanced renal replacement therapies to support patients with life threatening severe oliguric or anuric acute uremia or the International Renal Interest Society stage IV chronic kidney disease. Nutritional assessment and institution of nutritional support is crucial because dialysis only partially alleviates uremic anorexia. Dialytic patients have a higher risk of protein calorie, iron, zinc, vitamin B6, vitamin C, folic acid, 1,25-dihydroxycholecalciferol, and carnitine malnutritions. PMID:21251520

  7. Distinctive metabolite profiles in in-migrating Sockeye salmon suggest sex-linked endocrine perturbation.

    Science.gov (United States)

    Benskin, Jonathan P; Ikonomou, Michael G; Liu, Jun; Veldhoen, Nik; Dubetz, Cory; Helbing, Caren C; Cosgrove, John R

    2014-10-01

    The health of Skeena River Sockeye salmon (Onchorhychus nerka) has been of increasing concern due to declining stock returns over the past decade. In the present work, in-migrating Sockeye from the 2008 run were evaluated using a mass spectrometry-based, targeted metabolomics platform. Our objectives were to (a) investigate natural changes in a subset of the hepatic metabolome arising from migration-associated changes in osmoregulation, locomotion, and gametogenesis, and (b) compare the resultant profiles with animals displaying altered hepatic vitellogenin A (vtg) expression at the spawning grounds, which was previously hypothesized as a marker of xenobiotic exposure. Of 203 metabolites monitored, 95 were consistently observed in Sockeye salmon livers and over half of these changed significantly during in-migration. Among the most dramatic changes in both sexes were a decrease in concentrations of taurine (a major organic osmolyte), carnitine (involved in fatty acid transport), and two major polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In females, an increase in amino acids was attributed to protein catabolism associated with vitellogenesis. Animals with atypical vtg mRNA expression demonstrated unusual hepatic amino acid, fatty acid, taurine, and carnitine profiles. The cause of these molecular perturbations remains unclear, but may include xenobiotic exposure, natural senescence, and/or interindividual variability. These data provide a benchmark for further investigation into the long-term health of migrating Skeena Sockeye.

  8. [Limb torsion and developmental regression for one month after hand, foot and mouth disease in an infant].

    Science.gov (United States)

    Feng, Li-Fang; Chen, Xiao-Hong; Li, Dong-Xiao; Ding, Yuan; Jin, Ying; Song, Jin-Qing; Yang, Yan-Ling

    2016-05-01

    A one-year-old girl visited the hospital due to limb torsion and developmental regression for one month after hand, foot and mouth disease. At the age of 11 months, she visited a local hospital due to fever for 5 days and skin rash with frequent convulsions for 2 days and was diagnosed with severe hand, foot and mouth disease, viral encephalitis, and status epilepticus. Brain MRI revealed symmetric abnormal signals in the bilateral basal ganglia, bilateral thalamus, cerebral peduncle, bilateral cortex, and hippocampus. She was given immunoglobulin, antiviral drugs, and anticonvulsant drugs for 2 weeks, and the effect was poor. Blood and urine screening for inherited metabolic diseases were performed to clarify the etiology. The analysis of urine organic acids showed significant increases in glutaric acid and 3-hydroxyglutaric acid, which suggested glutaric aciduria type 1, but her blood glutarylcarnitine was normal, and free carnitine significantly decreased. After the treatment with low-lysine diets, L-carnitine, and baclofen for 1 month, the patient showed a significant improvement in symptoms. Hand, foot and mouth disease is a common viral infectious disease in children, and children with underlying diseases such as inherited metabolic diseases and immunodeficiency may experience serious complications. For children with hand, foot and mouth disease and unexplained encephalopathy, inherited metabolic diseases should be considered. PMID:27165592

  9. Long-chain Acylcarnitines Reduce Lung Function by Inhibiting Pulmonary Surfactant.

    Science.gov (United States)

    Otsubo, Chikara; Bharathi, Sivakama; Uppala, Radha; Ilkayeva, Olga R; Wang, Dongning; McHugh, Kevin; Zou, Ye; Wang, Jieru; Alcorn, John F; Zuo, Yi Y; Hirschey, Matthew D; Goetzman, Eric S

    2015-09-25

    The role of mitochondrial energy metabolism in maintaining lung function is not understood. We previously observed reduced lung function in mice lacking the fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD). Here, we demonstrate that long-chain acylcarnitines, a class of lipids secreted by mitochondria when metabolism is inhibited, accumulate at the air-fluid interface in LCAD(-/-) lungs. Acylcarnitine accumulation is exacerbated by stress such as influenza infection or by dietary supplementation with l-carnitine. Long-chain acylcarnitines co-localize with pulmonary surfactant, a unique film of phospholipids and proteins that reduces surface tension and prevents alveolar collapse during breathing. In vitro, the long-chain species palmitoylcarnitine directly inhibits the surface adsorption of pulmonary surfactant as well as its ability to reduce surface tension. Treatment of LCAD(-/-) mice with mildronate, a drug that inhibits carnitine synthesis, eliminates acylcarnitines and improves lung function. Finally, acylcarnitines are detectable in normal human lavage fluid. Thus, long-chain acylcarnitines may represent a risk factor for lung injury in humans with dysfunctional fatty acid oxidation. PMID:26240137

  10. Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

    Directory of Open Access Journals (Sweden)

    Koch Wolfgang

    2008-07-01

    Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

  11. Ghrelin reduces hepatic mitochondrial fatty acid beta oxidation.

    Science.gov (United States)

    Rigault, C; Le Borgne, F; Georges, B; Demarquoy, J

    2007-04-01

    Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation. PMID:17556859

  12. Metabolomics dataset of PPAR-pan treated rat liver.

    Science.gov (United States)

    Ament, Zsuzsanna; West, James A; Stanley, Elizabeth; Li, Xuefei; Ashmore, Tom; Roberts, Lee D; Wright, Jayne; Nicholls, Andrew W; Griffin, Julian L

    2016-09-01

    This article contains mass spectrometry (MS) data investigating small molecule changes as an effect of a triple peroxisome proliferator-activated receptor (PPAR-pan) agonist GW625019 in the liver as described in the manuscript (Ament et al., 2016) [1]. Samples were measured using gas chromatography-mass spectrometry (GC-MS) for total fatty acid content, and liquid chromatography-mass spectrometry (LC-MS) to measure intact lipids, carnitines and selected aqueous metabolites and eicosanoids. Data files comprise of Excel (Microsoft, WA, USA) spreadsheets of identified metabolites and their area ratio values for total fatty acids, carnitines, aqueous metabolites, and eicosanoids where the intensity of the analytes were normalised to the intensity of the internal standard. In the case of open profiling intact lipid data, the Excel file contains area ratio values of retention time and mass to charge ratio pairs; again, the area ratio values were calculated by normalising to the intensity of the internal standard. It should be noted that several metabolic changes are potentially indirect (secondary, tertiary and ensuing changes).

  13. Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload.

    Directory of Open Access Journals (Sweden)

    Karen van Eunen

    Full Text Available Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases. To obtain insight into the network dynamics of fatty-acid β-oxidation, we constructed a detailed computational model of the pathway and subjected it to a fat overload condition. The model contains reversible and saturable enzyme-kinetic equations and experimentally determined parameters for rat-liver enzymes. It was validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat-liver mitochondria: without refitting of measured parameters, the model correctly predicted the β-oxidation flux as well as the time profiles of most acyl-carnitine concentrations. Subsequently, we simulated the condition of obesity by increasing the palmitoyl-CoA concentration. At a high concentration of palmitoyl CoA the β-oxidation became overloaded: the flux dropped and metabolites accumulated. This behavior originated from the competition between acyl CoAs of different chain lengths for a set of acyl-CoA dehydrogenases with overlapping substrate specificity. This effectively induced competitive feedforward inhibition and thereby led to accumulation of CoA-ester intermediates and depletion of free CoA (CoASH. The mitochondrial [NAD⁺]/[NADH] ratio modulated the sensitivity to substrate overload, revealing a tight interplay between regulation of β-oxidation and mitochondrial respiration.

  14. Comparison of Bioactive Compounds and Quality Traits of Breast Meat from Korean Native Ducks and Commercial Ducks.

    Science.gov (United States)

    Lee, Hyun Jung; Jayasena, Dinesh D; Kim, Sun Hyo; Kim, Hyun Joo; Heo, Kang Nyung; Song, Ji Eun; Jo, Cheorun

    2015-01-01

    The aim of this research was to compare the bioactive compound content and quality traits of breast meat from male and female Korean native ducks (KND) and commercial ducks (CD, Cherry Valley). Meat from three 6-wk old birds of each sex from KND and CD were evaluated for carcass and breast weights, pH, color, cooking loss, shear force, and bioactive compound (creatine, carnosine, anserine, betaine, and L-carnitine) content. KND showed significantly higher carcass weights than CD whereas no such difference (p>0.05) was found between male and female ducks. The breed and sex had no significant effects on the breast weight, pH value, and shear force. However, KND had significantly lower cooking loss values than did CD. Creatine, anserine, and L-carnitine contents were significantly higher in KND than in CD and were predominant in female ducks compared to males. The results of this study provide rare information regarding the amounts and the determinants of several bioactive compounds in duck meat, which can be useful for selection and breeding programs, and for popularizing indigenous duck meat. PMID:26761808

  15. Vitagenes, dietary antioxidants and neuroprotection in neurodegenerative diseases.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Mancuso, Cesare; Barone, Eugenio; Calafato, Stella; Bates, Timothy; Rizzarelli, Enrico; Kostova, Albena T Dinkova

    2009-01-01

    The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) heme oxygenase-1 and Hsp70, as well as the thioredoxin/thioredoxin reductase system. Heat shock response contributes to establish a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Dietary antioxidants, such as curcumin, L-carnitine/acetyl-L-carnitine and carnosine have recently been demonstrated in vitro to be neuroprotective through the activation of hormetic pathways, including vitagenes. In the present review we discuss the importance of vitagenes in the cellular stress response and analyse, from a pharmacological point of view, the potential use of dietary antioxidants in the treatment of neurodegenerative disorders in humans. PMID:19273073

  16. Plasma concentrations of transsulfuration pathway products during nasoenteral and intravenous hyperalimentation of malnourished patients.

    Science.gov (United States)

    Chawla, R K; Berry, C J; Kutner, M H; Rudman, D

    1985-10-01

    We have monitored the plasma concentrations of products of the transsulfuration pathway in 11 undernourished noncirrhotic patients, and in 10 cachectic cirrhotic subjects, before and during nasoenteral nutrition with Vivonex (Norwich-Eaton Pharmaceuticals, Norwich, NY) or total parenteral nutrition (TPN) with FreAmine III (American McGaw, Irvine, CA). In the cirrhotic cases eating a mixed diet, levels of taurine, cysteine, plasma glutathione, and free choline were subnormal. During nasoenteral hyperalimentation, methionine was elevated while cysteine, glutathione, and free choline levels remained depressed. During TPN, levels of taurine, cysteine, protein-bound cysteine, glutathione, free choline, and phosphatidyl choline were depressed and methionine was elevated. In the noncirrhotic cases eating a mixed diet, only the free choline concentration was low. During nasoenteral hyperalimentation, the plasma levels of both free choline and total carnitine were depressed. During TPN, plasma levels of cystine, protein-bound cysteine, total carnitine, free choline, and phosphatidyl choline were subnormal. These data suggest that biosynthesis of several products of the transsulfuration pathway may be inadequate in both cirrhotic and noncirrhotic patients during TPN with FreAmine III. PMID:3931450

  17. Changes in the expression of HSL and OCTN2 in the female reproductive tract of the bat, Scotophilus heathii in relation to sperm storage.

    Science.gov (United States)

    Roy, Vikas Kumar; Krishna, Amitabh

    2012-07-01

    The aim of this study was to compare the changes in the expression of hormone sensitive lipase (HSL) and organic cation transporter 2 (OCTN2) in different regions of the female reproductive tract of bats (Scotophilus heathii) during the period of sperm storage. Western blot analysis revealed that both HSL and OCTN2 showed elevated expression in the utero-tubal junction, the site of sperm storage, compared to the vagina, cervix and uterus. An immunohistochemical study showed localization of HSL and OCTN2 in the cytoplasm of luminal epithelial cells in the utero-tubal junction of S. heathii, which suggests a role of fatty acids metabolism at the site of sperm storage. Furthermore, this study showed the presence OCTN2 immunostaining in the tail of stored sperm, which suggests a direct role of carnitine in sperm physiology. However, the role of carnitine in sperm storage needs further investigation. It is hypothesized that the utero-tubal junction may be finely tuned with fat depletion to support sperm storage in the female genital tract of S. heathii.

  18. Metabolic analysis of osteoarthritis subchondral bone based on UPLC/Q-TOF-MS.

    Science.gov (United States)

    Yang, Gang; Zhang, Hua; Chen, Tingmei; Zhu, Weiwen; Ding, Shijia; Xu, Kaiming; Xu, Zhongwei; Guo, Yanlei; Zhang, Jian

    2016-06-01

    Osteoarthritis (OA), one of the most widespread musculoskeletal joint diseases among the aged, is characterized by the progressive loss of articular cartilage and continuous changes in subchondral bone. The exact pathogenesis of osteoarthritis is not completely clear. In this work, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) in combination with multivariate statistical analysis was applied to analyze the metabolic profiling of subchondral bone from 42 primary osteoarthritis patients. This paper described a modified two-step method for extracting the metabolites of subchondral bone from primary osteoarthritis patients. Finally, 68 metabolites were identified to be significantly changed in the sclerotic subchondral bone compared with the non-sclerotic subchondral bone. Taurine and hypotaurine metabolism and beta-alanine metabolism were probably relevant to the sclerosis of subchondral bone. Taurine, L-carnitine, and glycerophospholipids played a vital regulation role in the pathological process of sclerotic subchondral bone. In the sclerotic process, beta-alanine and L-carnitine might be related to the increase of energy consumption. In addition, our findings suggested that the intra-cellular environment of sclerotic subchondral bone might be more acidotic and hypoxic compared with the non-sclerotic subchondral bone. In conclusion, this study provided a new insight into the pathogenesis of subchondral bone sclerosis. Our results indicated that metabolomics could serve as a promising approach for elucidating the pathogenesis of subchondral bone sclerosis in primary osteoarthritis. Graphical Abstract Metabolic analysis of osteoarthritis subchondral bone. PMID:27074781

  19. Development of relieving physical fatigue health drink%缓解体力疲劳功能饮料的研制

    Institute of Scientific and Technical Information of China (English)

    赵芳芳; 刘小杰

    2011-01-01

    体力疲劳是近年来的研究热点之一,以牛磺酸、左旋肉碱、咖啡因、B族维生素等为原料,制成新型抗疲劳保健饮料。稳定性实验结果表明:常温或37℃保存条件下,牛磺酸、咖啡因、左旋肉碱、肌醇、V B1和V B6的稳定性均较好,在保存期内损失较少。动物实验结果表明:该产品具有显著的抗疲劳作用。%Physical fatigue is one of the research focuses in recent years. In this study, a new anti-fatigue drink was studied that the main ingredient is taurine, L-carnitine, caffeine and vitamin B. The results of stability test under room temperature and 37 ℃ preservation conditions showed that the stability of taurine, caffeine, L-carnitine, inositol, vitamin B1 and vitamin B6 is very stable, and loss of them is less in the preservation period. The results of animal test results showed that the product has significant antifatigue effect.

  20. Genomic interval engineering of mice identified a novel modulator of triglyceride production

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Y.; Jong, M.C.; Frazer, K.A.; Gong, E.; Krauss, R.M.; Cheng, J.F.; Boffelli, D.; Rubin, E.M.

    1999-10-01

    To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

  1. Is there a place for nutritional supplements in the treatment of idiopathic male infertility?

    Directory of Open Access Journals (Sweden)

    Davide Arcaniolo

    2014-09-01

    Full Text Available Objective: Infertility affects 15% of couples in fertile age. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT. The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility. Material and methods: A Pub Med and Medline review of the published studies utilizing nutritional supplements for the treatment of male infertility has been performed. Results: Clinical trials on Vitamin E, Vitamin A, Vitamin C. Arginine, Carnitine, N-Acetyl-Carnitine, Glutathione, Coenzyme Q10, Selenium and Zinc were reviewed. Although there is a wide variability in selected population, dose regimen and final outcomes, nutritional supplements both alone and in combination seems to be able to improve semen parameters (sperm count, sperm motility and morphology and pregnancy rate in infertile men. Conclusions: There are rising evidences from published randomized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT. This improvement, however, is not consistent and there is a wide variation in the treatment regimens used. Well designed and adequately powered RCTs are needed to better clarify the role of nutritional supplements as treatment for male infertility.

  2. Distinctive metabolite profiles in in-migrating Sockeye salmon suggest sex-linked endocrine perturbation.

    Science.gov (United States)

    Benskin, Jonathan P; Ikonomou, Michael G; Liu, Jun; Veldhoen, Nik; Dubetz, Cory; Helbing, Caren C; Cosgrove, John R

    2014-10-01

    The health of Skeena River Sockeye salmon (Onchorhychus nerka) has been of increasing concern due to declining stock returns over the past decade. In the present work, in-migrating Sockeye from the 2008 run were evaluated using a mass spectrometry-based, targeted metabolomics platform. Our objectives were to (a) investigate natural changes in a subset of the hepatic metabolome arising from migration-associated changes in osmoregulation, locomotion, and gametogenesis, and (b) compare the resultant profiles with animals displaying altered hepatic vitellogenin A (vtg) expression at the spawning grounds, which was previously hypothesized as a marker of xenobiotic exposure. Of 203 metabolites monitored, 95 were consistently observed in Sockeye salmon livers and over half of these changed significantly during in-migration. Among the most dramatic changes in both sexes were a decrease in concentrations of taurine (a major organic osmolyte), carnitine (involved in fatty acid transport), and two major polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In females, an increase in amino acids was attributed to protein catabolism associated with vitellogenesis. Animals with atypical vtg mRNA expression demonstrated unusual hepatic amino acid, fatty acid, taurine, and carnitine profiles. The cause of these molecular perturbations remains unclear, but may include xenobiotic exposure, natural senescence, and/or interindividual variability. These data provide a benchmark for further investigation into the long-term health of migrating Skeena Sockeye. PMID:25198612

  3. Hepatothermic therapy of obesity: rationale and an inventory of resources.

    Science.gov (United States)

    McCarty, M F

    2001-09-01

    Hepatothermic therapy (HT) of obesity is rooted in the observation that the liver has substantial capacities for both fatty acid oxidation and for thermogenesis. When hepatic fatty acid oxidation is optimized, the newly available free energy may be able to drive hepatic thermogenesis, such that respiratory quotient declines while basal metabolic rate increases, a circumstance evidently favorable for fat loss. Effective implementation of HT may require activation of carnitine palmitoyl transferase-1 (rate-limiting for fatty acid beta-oxidation), an increase in mitochondrial oxaloacetate production (required for optimal Krebs cycle activity), and up-regulation of hepatic thermogenic pathways. The possible utility of various natural agents and drugs for achieving these objectives is discussed. Potential components of HT regimens include EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aspartate, chromium, coenzyme Q10, green tea polyphenols, conjugated linoleic acids, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs. Aerobic exercise training and very-low-fat, low-glycemic-index, high-protein or vegan food choices may help to establish the hormonal environment conducive to effective HT. High-dose biotin and/or metformin may help to prevent an excessive increase in hepatic glucose output. Since many of the agents contemplated as components of HT regimens are nutritional or food-derived compounds likely to be health protective, HT is envisioned as an on-going lifestyle rather than as a temporary 'quick fix'. Initial clinical efforts to evaluate the potential of HT are now in progress. PMID:11516225

  4. A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.

    Directory of Open Access Journals (Sweden)

    Alessandra Ferramosca

    Full Text Available Krill oil (KO is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.

  5. A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.

    Science.gov (United States)

    Ferramosca, Alessandra; Conte, Annalea; Burri, Lena; Berge, Kjetil; De Nuccio, Francesco; Giudetti, Anna Maria; Zara, Vincenzo

    2012-01-01

    Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.

  6. The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Larsen, Steen; Danielsen, J H; Søndergård, Stine Dam;

    2015-01-01

    High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak )]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT...... of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. Km (app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal...... muscle and adipose tissue. Maximal OXPHOS capacity with complex I- and II-linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO2peak . Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal...

  7. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha

    2013-06-03

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  8. Effect of dietary docosahexaenoic acid on lipogenesis and lipolysis in black sea bream, Acanthopagrus schlegeli

    Institute of Scientific and Technical Information of China (English)

    JI Hong; OM Ahamd Daud; YOSHIMATSU Takao; UMINO Testuya; NAKAGAWA Heisuke; FURUHASHI Makoto; SAKAMOTO Shuichi

    2007-01-01

    Hatchery-reared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid (DHA) on lipogenic and lipolysis enzymes, one-year fish were reared on a casein-based purified diet and a DHA fortified diet (1.5% DHA ethyl ester/kg diet) for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancreas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.

  9. The human and mouse SLC25A29 mitochondrial transporters rescue the deficient ornithine metabolism in fibroblasts of patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome.

    Science.gov (United States)

    Camacho, José A; Rioseco-Camacho, Natalia

    2009-07-01

    The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a disorder of the urea cycle (UCD) and ornithine degradation pathway caused by mutations in the mitochondrial ornithine transporter (ORNT1). Unlike other UCDs, HHH syndrome is characterized by a less severe and variable phenotype that we believe may, in part, be due to genes with redundant function to ORNT1, such as the previously characterized ORNT2 gene. We reasoned that SLC25A29, a member of the same subfamily of mitochondrial carrier proteins as ORNT1 and ORNT2, might also have overlapping function with ORNT1. Here, we report that both the human and mouse SLC25A29, previously identified as mitochondrial carnitine/acyl-carnitine transporter-like, when overexpressed transiently also rescues the impaired ornithine transport in cultured HHH fibroblasts. Moreover, we observed that, in the mouse, the Slc25a29 message is more significantly expressed in the CNS and cultured astrocytes when compared with the liver and kidney. These results suggest a potential physiologic role for the SLC25A29 transporter in the oxidation of fatty acids, ornithine degradation pathway, and possibly the urea cycle. Our results show that SLC25A29 is the third human mitochondrial ornithine transporter, designated as ORNT3, which may contribute to the milder and variable phenotype seen in patients with HHH syndrome.

  10. Recent Progress in Cryopreservation of Bovine Oocytes

    Directory of Open Access Journals (Sweden)

    In-Sul Hwang

    2014-01-01

    Full Text Available Principle of oocyte cryoinjury is first overviewed and then research history of cryopreservation using bovine oocytes is summarized for the last two decades with a few special references to recent progresses. Various types of cryodevices have been developed to accelerate the cooling rate and applied to the oocytes from large domestic species enriched with cytoplasmic lipid droplets. Two recent approaches include the qualitative improvement of IVM oocytes prior to the vitrification and the short-term recovery culture of vitrified-warmed oocytes prior to the subsequent IVF. Supplementation of L-carnitine to IVM medium of bovine oocytes has been reported to reduce the amount of cytoplasmic lipid droplets and improve the cryotolerance of the oocytes, but it is still controversial whether the positive effect of L-carnitine is reproducible. Incidence of multiple aster formation, a possible cause for low developmental potential of vitrified-warmed bovine oocytes, was inhibited by a short-term culture of the postwarm oocytes in the presence of Rho-associated coiled-coil kinase (ROCK inhibitor. Use of an antioxidant α-tocopherol, instead of the ROCK inhibitor, also supported the revivability of the postwarm bovine oocytes. Further improvements of the vitrification procedure, combined with pre- and postvitrification chemical treatment, would overcome the high sensitivity of bovine oocytes to cryopreservation.

  11. Antimutagenic Activity of Some Natural supplements on Ivermectin genotoxicity in Lymphocytes of Buffalo

    Directory of Open Access Journals (Sweden)

    Aida I. El-makawy and Karima F. Mahrous

    2008-03-01

    Full Text Available Ivermectin is a veterinary anthelminthic drug, highly effective against a number of arthropod and nematode infestations in vertebrates. The literature reported that ivermectin have mutagenic activities. The extensive use of ivermectin in food producing animals can cause potential hazard to humanity by causing gene mutation or chromosomal aberrations. Recently, there have been con-siderable efforts to search for naturally occurring substances that can inhibit, reverse, retard or pre-vent mutagenicity. A wide array of substances derived from edibles and medicinal plants reported to possess anticarcinogenic and antimutagenic activities. Therefore, the aim of this study was to evaluate the modulator role of each of garlic, L-carnitine and wheat germ oil (WGO against geno-toxicity of ivermectin in buffalo lymphocyte cultures by using the cytokinesis block micronucleus assay and chromosomal aberrations test as cytogenetic end-points. Results showed that ivermectin induced dose dependent increase in the frequencies of the binucleated lymphocytes with micronuc-lei as well as the number of micronuclei in lymphocytes of river buffalo, while the number of bi-nucleated lymphocytes significantly decreased. In addition, ivermectin low dose caused non-significant increase in the frequency of total chromosomal aberrations in lymphocytes of river buf-falo as compared to control. Whereas, in medium and high doses the frequencies of aberrant cells increased at a significant level (P 0.001 than control. Meanwhile, the treatment with the three natural supplements (garlic, L-carnitine, wheat germ oil in continuous with ivermectin significant-ly reduced the frequencies of binucleated lymphocytes with micronuclei, the number of micronuc-lei and the frequencies of total chromosomal aberrations induced by ivermectin tested doses, and increase the number of binucleated lymphocytes. In addition, the results indicated that there were non-significant differences between the

  12. 普洱乌龙茶功能饮料的工艺研究%Study on Process of a Functional Beverage from Pu’er and Oolon

    Institute of Scientific and Technical Information of China (English)

    成官哲; 郭爱秀; 刘小杰

    2014-01-01

    A functional beverage was developed from pu’er,oolong, buckwheat, green tea extract, ginkgo biloba extract and L-carnitine and its production process was optimized using single factor experiment and orthogonal experiment. The optimal beverage extraction process is: extracting under the condition of temperature 90℃, solid liquid ratio 1:30, time 6mins,chilling the extract to 10℃, centrifuging though high-speed centrifugal disc and then filtering though 1U refined filter. This process is able to maintain the beverage flavor while reducing sediment. Preserving with the temperature of 37℃, the beverage shows better stability of tea polyphenol, total flavonoids, and L-carnitine and less loss of these ingredients during the preserving period. then centrifuge with high-speed disc centrifuge and 1u fine filter,so it decrease the sedimentation while preserving the flavor. The result of stability test under 37℃ preservation conditions showed that the stability of tea polyphenols、total flavonoids、L-carnitine is very stable, and loss of them is less in the preservation period.%以普洱茶、乌龙茶、苦荞麦、绿茶提取物、银杏叶提取物、左旋肉碱为原料,采用单因素实验和正交实验研究普洱乌龙茶功能饮料的生产工艺。结果表明,料水比1∶30、浸提温度90℃、浸提6min,迅速冷却到10℃以下,进行高速碟片离心和1U精滤,能在保留产品风味同时显著减少饮料沉淀产生;37℃下保存,茶多酚、总黄酮、左旋肉碱的稳定性均较好,在保存期内损失较少。

  13. Modulation of human basophil histamine release by protein kinase C inhibitors differs with secretagogue and with inhibitor.

    Science.gov (United States)

    Bergstrand, H; Lundquist, B; Karabelas, K; Michelsen, P

    1992-03-01

    To assess possible involvement of protein kinase C (PKC) in human basophil degranulation, the present work compared effects of various purported PKC inhibitors on leukocyte histamine release triggered by different stimuli. The effects recorded varied with the inhibitor and the secretagogue used; moreover, with a given secretagogue, different inhibitors often displayed different activities. Thus, histamine release triggered by the PKC activator 4 beta-phorbol 12-myristate 13-acetate was blocked by K252a, staurosporine and the purported specific PKC inhibitor Ro 31-7549, and reduced by calphostin C, H-7, TMB-8 and W-7 but not affected by polymyxin B; it was augmented by 2.1 microM palmitoyl carnitine. The leukocyte response induced by another putative activator of PKC, 1,2-isopropylidene-3-decanoyl-sn-glycerol, was also enhanced by 2.1 microM palmitoyl carnitine, slightly increased by staurosporine, TMB-8 and W-7 but not affected by calphostin C, H-7, K252a or Ro 31-7549, whereas the hyperosmolar mannitol-induced response was reduced by H-7, calphostin C, TMB-8 and W-7 and slightly augmented by staurosporine. Anti-IgE-induced histamine release was blocked by staurosporine and K252a and reduced by calphostin C, sphingosine, TMB-8 and W-7 but not affected by H-7, polymyxin B or retinal. It was enhanced by Ro 31-7549. In contrast, leukocyte histamine release induced by calcium ionophore A23187 or by ionomycin was blocked by retinal, TMB-8 and W-7 and reduced by calphostin C and palmitoyl carnitine but enhanced by H-7, staurosporine and polymyxin B; K252a and Ro 31-7549 did not affect such responses. Formyl-methionyl-leucyl-phenylalanine-triggered histamine release was barely affected by any agent used. Thus, the specific PKC inhibitor Ro 31-7549 selectively blocked 4 beta-phorbol 12-myristate 13-acetate-triggered leukocyte histamine release. These results imply that examined secretagogues trigger human leukocyte histamine release through partly separate pathways

  14.  Hepatotoxicity associated with dietary energy supplements: use and abuse by young athletes.

    Science.gov (United States)

    Avelar-Escobar, Giovanni; Méndez-Navarro, Jorge; Ortiz-Olvera, Nayeli X; Castellanos, Guillermo; Ramos, Roberto; Gallardo-Cabrera, Víctor E; Vargas-Alemán, José de Jesús; Díaz de León, Oscar; Rodríguez, Elda V; Dehesa-Violante, Margarita

    2012-01-01

     In recent years there has been a significant increase in the consumption of dietary energy supplements (DES) associated with the parallel advertising against obesity and favoring high physical performance. We present the case and outcome of a young patient who developed acute mixed liver injury (hepatocellular and cholestatic) after ingestion of various "over the counter" products to increase muscle mass and physical performance (NO Xplode®, creatine, L-carnitine, and Growth Factor ATN®). The diagnosis was based on the exclusion of other diseases and liver biopsy findings. The dietary supplement and herbal multivitamins industry is one with the highest growth rates in the market, with annual revenues amounting to billions and constantly lacking scientific or reproducible evidence about the efficacy and/or safety of the offered products. Furthermore, and contrary to popular belief, different forms of injury associated with these natural substances have been documented particularly in the liver, supporting the need of a more strict regulation.

  15. The nutritional management of urea cycle disorders.

    Science.gov (United States)

    Leonard, J V

    2001-01-01

    Diet is one of the mainstays of the treatment of patients with urea cycle disorders. The protein intake should be adjusted to take account of the inborn error and its severity and the patient's age, growth rate, and individual preferences. Currently, the widely used standards for protein intake are probably more generous than necessary, particularly for those with the more severe variants. Most patients, except those with arginase deficiency, will need supplements of arginine, but the value of other supplements including citrate and carnitine is unclear. Any patient on a low-protein diet should be monitored clinically and with appropriate laboratory tests. All should have an emergency (crisis) regimen to prevent decompensation during periods of metabolic stress.

  16. Maintenance of Cognitive Performance and Mood for Individuals with Alzheimer's Disease Following Consumption of a Nutraceutical Formulation: A One-Year, Open-Label Study.

    Science.gov (United States)

    Remington, Ruth; Bechtel, Cynthia; Larsen, David; Samar, Annemarie; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2016-01-01

    Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer's disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.

  17. A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension.

    Science.gov (United States)

    Remington, Ruth; Lortie, Jevin J; Hoffmann, Heather; Page, Robert; Morrell, Christopher; Shea, Thomas B

    2015-01-01

    Thirty-four individuals with mild cognitive impairment were randomized for 6 months to a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo, followed by a 6-month open-label extension in which all individuals received NF. The NF cohort improved in the Dementia Rating Scale (DRS; effect size >0.7) and maintained baseline performance in CLOX-1. The placebo cohort did not improve in DRS and declined in CLOX-1, but during the open-label extension improved in DRS and ceased declining in CLOX-1. These findings extend prior studies of NF efficacy for individuals without cognitive impairment and with Alzheimer's disease.

  18. Ketogenic Diet: An Early Option for Epilepsy Treatment, Instead of A Last Choice Only

    Directory of Open Access Journals (Sweden)

    Huei-Shyong Wang

    2012-02-01

    Full Text Available Ketogenic diet (KD was usually tried as a last resort in the treatment of intractable epilepsy after failure of many antiepileptics and even epilepsy surgery. Glucose transporter-1 deficiency and pyruvate dehydrogenase deficiency must be treated with KD as the first choice because of inborn errors of glucose metabolism. Infantile spasms, tuberous sclerosis complex, Rett syndrome, Doose syndrome, Dravet syndrome, etc., appear to respond to KD, and it has been suggested by the international consensus statement to use KD early. We believe that all patients with epilepsy, except those with contraindicated situations such as pyruvate carboxylase deficiency, porphyria, β-oxidation defects, primary carnitine deficiency, etc., may try KD before trying other regimens.

  19. A Case of Valproate Induced Hyperammonemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Surjit Tarafdar

    2011-01-01

    Full Text Available A 36-years-old man on phenytoin, levetiracetam, and sodium valproate presented with acute confusion. Routine investigations including serum valproate and phenytoin concentration were normal. His serum ammonia concentration was raised. His valproate was held and 2 days later he recovered with concordant normalisation of serum ammonia concentration. Urea acid cycle disorder was ruled out, and a diagnosis of valproate induced hyperammonemic encephalopathy (VHE was made. Asymptomatic hyperammonemia occurs in 15–50% of valproate-treated patients, and while the true incidence of VHE is not known, it is a recognized complication of sodium valproate treatment. VHE typically presents acutely with impaired consciousness, lethargy, and vomiting. Valproate concentrations may be in the therapeutic range, and liver function tests are typically “normal.” Treatment for VHE consists of ceasing valproate and providing supportive care. Some have advocated carnitine replacement.

  20. Motonuclear changes after cranial nerve injury and regeneration.

    Science.gov (United States)

    Fernandez, E; Pallini, R; Lauretti, L; La Marca, F; Scogna, A; Rossi, G F

    1997-09-01

    Little is known about the mechanisms at play in nerve regeneration after nerve injury. Personal studies are reported regarding motonuclear changes after regeneration of injured cranial nerves, in particular of the facial and oculomotor nerves, as well as the influence that the natural molecule acetyl-L-carnitine (ALC) has on post-axotomy cranial nerve motoneuron degeneration after facial and vagus nerve lesions. Adult and newborn animal models were used. Massive motoneuron response after nerve section and reconstruction was observed in the motonuclei of all nerves studied. ALC showed to have significant neuroprotective effects on the degeneration of axotomized motoneurons. Complex quantitative, morphological and somatotopic nuclear changes occurred that sustain new hypotheses regarding the capacities of motoneurons to regenerate and the possibilities of new neuron proliferation. The particularities of such observations are described and discussed.

  1. 左旋肉碱联合促红细胞生成素治疗尿毒症贫血临床观察

    Institute of Scientific and Technical Information of China (English)

    何开德; 李林坤

    2010-01-01

    @@ 尿毒症贫血由多种因为引起,其中主要因为是促红细胞生成素(erythropoietin,EPO)分泌减少.重组人促红细胞生成素(recombinant human erythropoetin,rHuEPO)对大部分尿毒症贫血治疗有效.近年有研究表明,左旋肉碱(left carnitine,LC)缺乏是人体对EPO呈低反应性的因为之一,补充LC有利于提高rHuEPO的作用.笔者联合使用LC和rHuEPO治疗尿毒症贫血患者,疗效较好,报道如下.

  2. Myocardial energetics and the role of micronutrients in heart failure: a critical review

    Science.gov (United States)

    Wong, Ang-Peng; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Heart failure is a multifactorial disease with poor prognosis. There are many hypotheses regarding the cause of heart failure. Leading among them are the hemodynamic and the neuro-hormonal hypotheses. Although the energy depletion hypothesis has been fairly recent, there is evidence suggesting that declining bioenergy plays a major role in heart failure. This review explored the myocardial energy depletion hypothesis from the role of micronutrients in correcting and alleviating symptoms of heart failure. Even though focus was on key nutrients such as coenzyme Q10, thiamine, riboflavin, L-carnitine, and taurine, emphasis was on the combined effect of multiple micronutrients as a whole. Search from databases from 2000 to 2015 produced four clinical studies using multiple micronutrients on heart failure. Evidence from the studies show that using high doses of multiple micronutrients may have positive effects on heart failure and simultaneously support the myocardial energy depletion hypothesis. PMID:27679743

  3. Fever,poor response, convulsions, and hepatomegaly%发热,反应差,抽搐,肝大

    Institute of Scientific and Technical Information of China (English)

    钱乔乔; 刘智胜; 张芙蓉; 李瑞珍; 王宝香

    2016-01-01

    Objective To investigate the differential diagnosis of Reye syndrome and the characteristics of primary carnitine deficiency,and to provide diagnostic strategy for similar cases.Methods There was a case presented with fever,poor response,convulsions and hepatomegaly hospitalized in Wuhan Children's Hospital,and the clinical manifestations were described,the physical examination was comprehensively conducted,the auxiliary examination results were recorded,some pediatric specialists from ICU,neurology department,genetic metabolic department,digestive system department were invited to discuss the case.The treatment was adjusted according to the suggested opinions;the treatment effects and the final diagnosis were tracked.Results The primary diagnosis of the case was central nervous system infection or toxic encephalopathy at the time of admission,but Reye syndrome could not be excluded.Although the cerebrospinal fluid test and brain MRI examination detected nothing abnormal,liver function suggested alanine aminotrans ferase ALT increase,blood sugar decrease,the liver volume increase,which was detected by liver ultrasound.Blood amino acids examination revealed the carnitine level decreased,and it was confirmed as primary carnitine deficiency in the end.L-carnitine was used to treat the disease,and its effect was good.Conclusions Great importance should be attached to children with onset age,physical check-up,and multidisciplinary cooperation.Use monism to explain the illness and the auxiliary inspection as far as possible,so that it can get early diagnosis and treatment,and the outcome is good.%目的 探讨瑞氏综合征的鉴别诊断及原发性肉碱缺乏症特点,并为类似病例提供诊断思路.方法 对武汉市儿童医院收治的1例临床表现为发热、反应差、抽搐、肝脏增大的患儿,总结其临床表现,全面进行体格检查,记录其辅助检查结果,并请小儿重症医学科、神经内科、遗传代谢科、消化内科专

  4. Commercially marketed supplements for bodybuilding athletes.

    Science.gov (United States)

    Grunewald, K K; Bailey, R S

    1993-02-01

    We conducted a survey of 624 commercially available supplements targeted towards bodybuilding athletes. Over 800 performance claims were made for these supplements. Supplements include amino acids, boron, carnitine, choline, chromium, dibencozide, ferulic acid, gamma oryzanol, medium chain triglycerides, weight gain powders, Smilax compounds and yohimbine. Many performance claims advertised were not supported by published research studies. In some instances, we found no research to validate the claims; in other cases, research findings were extrapolated to inappropriate applications. For example, biological functions of some non-essential compounds were interpreted as performance claims for the supplements. Claims for others were based on their ability to enhance hormonal release or activity. We suggest that more research be conducted on this group of athletes and their nutritional needs. Furthermore, the effectiveness and safety of supplements merit further investigation.

  5. Inhibition of MMP-13 with modified polymer particles

    Science.gov (United States)

    Tran, Hai; Bratlie, Kaitlin M.

    2016-06-01

    Matrix metalloproteinases (MMPs) are proteases that destroy the extracellular matrix and have important roles in the foreign body response, wound healing, and disease. Of particular importance is the chronic wound environment in which MMP activity is increased, resulting in destruction of the de novo extracellular matrix. One potential treatment of these wounds would be to use dressings that are capable of inhibiting MMP activity. In this study, we examined the effect of seven polymer modifiers (2-amino-3-guanidinopropionic acid, arginine, carnitine, citrulline, creatine, 3-guanidino propionic acid, and Nw-nitro-L-arginine) on MMP-13 activity. MMP-13 is a collagenase that is present in chronic wounds and is zinc dependent. Our results showed that these polymer modifiers were able to inhibit MMP-13 activity to varying degrees. The mechanism of inhibition appears to be binding zinc to the modifiers.

  6. Bezafibrate in skeletal muscle fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Ørngreen, Mette Cathrine; Madsen, Karen Lindhardt; Preisler, Nicolai;

    2014-01-01

    OBJECTIVE: To assess whether bezafibrate increases fatty acid oxidation (FAO) and lowers heart rate (HR) during exercise in patients with carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies. METHODS: This was a 3-month, randomized, double......-blind, crossover study of bezafibrate in patients with CPT II (n = 5) and VLCAD (n = 5) deficiencies. Primary outcome measures were changes in FAO, measured with stable-isotope methodology and indirect calorimetry, and changes in HR during exercise. RESULTS: Bezafibrate lowered low-density lipoprotein......, triglyceride, and free fatty acid concentrations; however, there were no changes in palmitate oxidation, FAO, or HR during exercise. CONCLUSION: Bezafibrate does not improve clinical symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies. These findings indicate that previous in vitro...

  7. Male infertility: lifestyle factors and holistic, complementary, and alternative therapies

    Science.gov (United States)

    Yao, David F; Mills, Jesse N

    2016-01-01

    While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT) include aescin, coenzyme Q10, glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive. PMID:26952957

  8. A Case of Montelukast-Induced Churg-Strauss Syndrome Associated with Liver Dysfunction

    Directory of Open Access Journals (Sweden)

    Keiji Matsui

    2011-01-01

    Full Text Available A 64-year-old woman was admitted to hospital due to protracted diarrhea and liver dysfunction. The patient was diagnosed as Churg-Strauss syndrome (CSS due to asthma, paranasal sinusitis, hypereosinophilia, and polyneuropathy. There was a history of taking montelukast, a leukotriene receptor antagonist (LTRA, which is thought to have some relationship with CSS. The liver biopsy specimen showed eosinophilic infiltration and centrolobular fatty change. In this paper, we review the relationship between LTRA and CSS. Several lines of evidence suggest that leukotriene plays an important role in maintaining neural tissues. We also review the potential relationship between centrolobular fatty change and pivoxil-containing antibiotics, which was prescribed for sinusitis before admission. Carnitine deficiency induced by pivoxil-containing agents may cause impaired fatty acid oxidation in mitochondria.

  9. Male infertility: lifestyle factors and holistic, complementary, and alternative therapies

    Directory of Open Access Journals (Sweden)

    David F Yao

    2016-01-01

    Full Text Available While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT include aescin, coenzyme Q 10 , glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.

  10. 国内外婴幼儿配方乳粉中DHA、AA、牛磺酸、核苷酸、左旋肉碱、β-胡萝卜素含量的比较

    Institute of Scientific and Technical Information of China (English)

    苏永祺; 李珮斯; 侯向昶; 谢文缄; 郭新东; 袁洁; 温力力

    2014-01-01

    Comparison of domestic and foreign infant formula milk powder of DHA, AA, taurine, nucleotide, L-carnitine and β-carotene is added situation, understanding the differences. Selection of 60 domestic and foreign brands of infant formula milk powder, DHA, AA, taurine, nucleotide, L-carnitine and β-carotene in samples were determined by national food safety standard detection methods. The results show that, domestic and foreign milk powder, the detection ratio of AA, DHA is 100%, the detection rate of taurine, nucleotide, L-carnitine is 60% ~ 100%, the detection rate of β-carotene is 20% ~ 60%. Between domestic and foreign milk powder, the content range of AA in infant formula milk powder and DHA in larger babies and infant formula milk powder have some similarities, the content range of the remaining ingredients are far away. The content average of AA, nucleotide, L-carnitine in infant formula milk powder and DHA, taurine in larger babies and infant formula milk powder is roughly equal, the content average of remaining ingredients is not the same.%对国内外婴幼儿配方乳粉中DHA、AA、牛磺酸、核苷酸、左旋肉碱和β-胡萝卜素的的添加情况进行比较,了解其差异性。挑选60个国内外品牌的婴幼儿配方乳粉,按照食品安全国家标准检测方法,检测乳粉中 DHA、AA、牛磺酸、核苷酸、左旋肉碱和β-胡萝卜素的含量。结果表明,国内外乳粉中 AA、DHA的检出比例均为100%,牛磺酸、核苷酸、左旋肉碱的检出比例为60%~100%,β-胡萝卜素的检出比例为20%~60%;国内外乳粉之间,婴儿配方乳粉中的AA以及较大婴儿和幼儿配方乳粉中的DHA的含量范围有一定的相似性,其余成分的含量范围相差较远;婴儿配方乳粉中的AA、核苷酸、左旋肉碱,以及较大婴儿和幼儿配方乳粉中的DHA、牛磺酸含量的平均值基本相当,其余成分含量的平均值各有高低之分。

  11. Male infertility: lifestyle factors and holistic, complementary, and alternative therapies.

    Science.gov (United States)

    Yao, David F; Mills, Jesse N

    2016-01-01

    While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT) include aescin, coenzyme Q 10 , glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive. PMID:26952957

  12. Centronuclear myopathy in a Border collie dog.

    Science.gov (United States)

    Eminaga, S; Cherubini, G B; Shelton, G D

    2012-10-01

    A two-year old, male entire Border collie was presented with a one-year history of exercise-induced collapsing on the pelvic limbs. Physical examination revealed generalised muscle atrophy. Neurological examination supported a generalised neuromuscular disorder. Electromyography revealed spontaneous electrical activity in almost all muscles. Unfixed and formaldehyde-fixed biopsy samples were collected from the triceps brachii, longissimus and vastus lateralis muscles. Histopathological, histochemical and ultrastructural examinations of biopsy specimens were consistent with either centronuclear or myotubular myopathy. The dog clinically improved with supportive treatment with L-carnitine, co-enzyme Q10 and vitamin B compound. To the authors' knowledge, this is the first report of centronuclear/myotubular myopathy in a Border collie. PMID:23013377

  13. Veterinary clinical nutrition: success stories: an overview.

    Science.gov (United States)

    Davies, Mike

    2016-08-01

    In this overview of success stories in veterinary clinical nutrition topics in cats and dogs reviewed include the dietary management of chronic kidney disease, dissolution of urinary tract uroliths by dietary modification, the recognition that taurine and L-carnitine deficiencies can cause dilated cardiomyopathy; that clinical signs associated with feline hyperthyroidism (caused by a benign adenoma) can be controlled by a low-iodine diet alone; that dietary management of canine osteoarthritis can also reduce non-steroidal anti-inflammatory drug doses; and that disease-free intervals and survival times can be statistically longer in dogs with Stage III lymphoma managed with diet. As we discover more about nutrigenetics and nutrigenomics, and as we expand our basic understanding of idiopathic diseases we are bound to identify more nutritionally related causes, and be able to develop novel dietary strategies to manage disease processes, including the formulation of diets designed to alter gene expression to obtain beneficial clinical outcomes. PMID:27269202

  14. Discovery of the strong antioxidant selenoneine in tuna and selenium redox metabolism

    Institute of Scientific and Technical Information of China (English)

    Yumiko; Yamashita; Takeshi; Yabu; Michiaki; Yamashita

    2010-01-01

    A novel selenium-containing compound,selenoneine,has been isolated as the major form of organic selenium in the blood and tissues of tuna.Selenoneine harbors a selenium atom in the imidazole ring,2-selenylNα,Nα,Nα-trimethyl-L-histidine,and is a selenium analog of ergothioneine.This selenium compound has strong antioxidant capacity and binds to heme proteins,such as hemoglobin and myoglobin,to protect them from iron auto-oxidation,and it reacts with radicals and methylmercury(MeHg) .The organic cations/carnitine transporter OCTN1 transports selenoneine and MeHg,regulates Se-enhanced antioxidant activity,and decreases MeHg toxicity.Thus,the dietary intake of selenoneine,by consuming fish,might decrease the formation of reactive oxygen radicals that could oxidize nucleotides in DNA,and thereby inhibit carcinogenesis,chronic diseases,and aging.

  15. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  16. Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping

    DEFF Research Database (Denmark)

    Madsen, Pia Pinholt; Kibaek, Maria; Roca, Xavier;

    2006-01-01

    with SBCADD, both with seizures and psychomotor delay as the main clinical features. One family illustrates the fact that affected individuals may also remain asymptomatic. In addition, the normal level of newborn blood spot C5-acylcarnitine in one patient underscores the fact that newborn screening by MS...... of C5-carnitine in blood may indicate SBCADD, the disorder may be detected by MS/MS-based routine newborn screening. It is, therefore, important to gain more knowledge about the clinical presentation and the mutational spectrum of SBCADD. In the present study, we have studied two unrelated families....../MS currently lacks sensitivity in detecting SBCADD. Until now, seven mutations in the SBCAD gene have been reported, but only three have been tested experimentally. Here, we identify and characterize an IVS3+3A>G mutation (c.303+3A>G) in the SBCAD gene, and provide evidence that this mutation is disease...

  17. Beskrivelse af næringsstofomsætning med metabolomics

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou

    2010-01-01

    I et forsøg med mink med lav eller høj foderkonvertering er der blevet taget blodprøver på tre tidspunkter. Blodprøverne er blevet taget i en periode, hvor minkene er blevet fodret restriktivt (en prøve) og i en periode med ad libitum fodring (to prøver). Blodprøverne blev analyseret ved hjælp af...... fra restriktivt fodrede mink end i plasma fra ad libitum fodrede mink - betain og carnitin. Derudover er der en lang række andre metabolitter, som også findes i forskellig koncentration som endnu ikke er identificeret....

  18. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hey-Mogensen, Martin; Sahlin, Kent; Fernström, Maria;

    2007-01-01

    We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy....... Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P ... no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C...

  19. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

    DEFF Research Database (Denmark)

    Smelt, A H; Poorthuis, B J; Onkenhout, W;

    1998-01-01

    Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis.......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9...

  20. A severe genotype with favourable outcome in very long chain acyl-CoA dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Touma, E H; Rashed, M S; Vianey-Saban, C;

    2001-01-01

    A patient with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is reported. He had a severe neonatal presentation and cardiomyopathy. He was found to be homozygous for a severe mutation with no residual enzyme activity. Tandem mass spectrometry on dried blood spots revealed increased lo...... chain acylcarnitines. VLCAD enzyme activity was severely decreased to 2% of control levels. Dietary management consisted of skimmed milk supplemented with medium chain triglycerides and L-carnitine. Outcome was good and there was no acute recurrence.......A patient with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is reported. He had a severe neonatal presentation and cardiomyopathy. He was found to be homozygous for a severe mutation with no residual enzyme activity. Tandem mass spectrometry on dried blood spots revealed increased long...

  1. A Case of Glutaric Aciduria Type I with a Novel Mutation

    Directory of Open Access Journals (Sweden)

    Nilgun Uyduran Unal

    2013-08-01

    Full Text Available Glutaric aciduria type I is an autosomal recessive inherited disorder caused by the deficiency of glutaryl CoA dehydrogenase. The incidence of the disease is 1/100.000. Glutaryl CoA dehydrogenase gene is located on locus 19p13.2. More than 200 mutations have been described for this gene. Most common mutation in the population is C1240T. Clinical symptoms included neurological regression complications such as loss of sucking and swallowing reflexes choreoathetosis, seizures, rigidity and opisthotonos. In treatment high-carbohydrate, low-protein diet and carnitine is given. We would like to report this interesting case in order to present a new mutation for glutaric aciduria type I. [Cukurova Med J 2013; 38(4.000: 809-812

  2. Research Results and Information Update

    Science.gov (United States)

    2011-01-01

    Research Results Monsoon behavior balanced by glaciers Research Discovers Frequent Mutations of Chromatin Significant Progress in Water Photochemistry Research Structural signature in amorphous alloy formation and plastic deformation The neural basis of Drosophila larval light/darkness preference Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity Determination of electron pairing symmetry of iron-based superconductor FeSe Long-Range Topological Order in Metallic Glass Information Update List of Projects Jointly Funded by NSFC and CNRS in 2011 List of Projects Jointly Funded by NSFC and ESRC in 2011 List of Projects Jointly Funded by NSFC and RS in 2011 List of Projects Jointly Funded by NSFC and RSE in 2011 Funding of Major Program Projects in 2010 Funding of Key Program Projects in 2010

  3. Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun Hyoung Park

    2016-03-01

    Full Text Available Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC. Analysis of cybrids and established breast cancer (BC cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1 and 2 (CPT2, the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.

  4. Thermodynamics of interactions between organic ammonium ions and sulfonatocalixarenes

    International Nuclear Information System (INIS)

    Calorimetric titration and NMR experiments in aqueous phosphate buffer (pH 7.2) at 298.15 K have been done to determine the binding mode, complex stability constants and thermodynamics (ΔGo, ΔHo, and TΔSo) for 1:1 inclusion complexation of water-soluble calix[n]arenesulfonates (CnAS, n = 4 and 6) and thiacalix[4]arene tetrasulfonate (TCAS) with acethylcholine, carnitine, betaine and benzyltrimethylammonium ion. The results show the inclusion complexations are driven by enthalpy (ΔHo o C6AS > TCAS) are discussed from the viewpoint of CH-π/π-π interactions, electrostatic interactions and size/shape-fit relationship between host and guest

  5. 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

    Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human...... 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...... respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P

  6. Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Rolland, Marine; Skov, Peter Vilhelm; Larsen, Bodil Katrine;

    2016-01-01

    concentrations. The transcript levels of enzymes involved in lipid metabolism (fatty acid synthase, glucose 6 phosphate dehydrogenase and carnitine palmitoyl transferase 1 a), gluconeogenesis (fructose-1,6-biphosphatase) and amino acid catabolism (alanine amino transferase and glutamate dehydrogenase) were......Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works...... as a signalling factor in different metabolic pathways. The study investigated the effect of increasing dietary methionine intake on the intermediary metabolism in the liver of juvenile rainbow trout. For this purpose, five diets were formulated with increasing methionine levels from 0.60 to 1.29% dry matter...

  7. Simultaneous determination of C2-C22 non-esterified fatty acids and other metabolically relevant carboxylic acids in biological material by gas chromatography of their benzyl esters.

    Science.gov (United States)

    Schatowitz, B; Gercken, G

    1988-03-18

    A method for the simultaneous determination of non-esterified short-, medium- and long-chain fatty acids and other types of metabolically relevant carboxylic acids such as hydroxy, keto, aromatic and dicarboxylic acids in biological material by capillary gas chromatography of benzyl ester derivatives is described. Sample preparation avoiding incomplete isolation of carboxylic acids consisted of deproteinization and extraction with ethanol, fixation of carboxylic acids as carboxylates, removal of interfering compounds such as neutral lipids by hexane extraction and amino acids, acyl carnitines and other cations by cation-exchange chromatography, derivatization of keto groups of ketocarboxylic acids into O-methyl oximes and benzyl ester formation by reaction of the potassium carboxylates with benzyl bromide via crown ether catalysis. The sample preparation conditions were investigated, showing the usefulness of this method for quantitative determinations. Chromatograms obtained from human serum, human urine and rat heart ventricle and concentrations of carboxylic acids in these specimens are presented. PMID:3372640

  8. Nutrition in Pancreatic Cancer: A Review

    Science.gov (United States)

    Gärtner, Simone; Krüger, Janine; Aghdassi, Ali A.; Steveling, Antje; Simon, Peter; Lerch, Markus M.; Mayerle, Julia

    2016-01-01

    Background Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. Summary This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival Key Message Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data Practical Implications Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and l-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer.

  9. [Analysis of SNPs and enzymatic disorder in the patients of influenza-associated encephalopathy: disorder of fatty acid metabolism in mitochondria induced by high fever].

    Science.gov (United States)

    Kido, Hiroshi; Yao, Dengbing; Le Trong, Quang; Tsukane, Mariko; Chida, Junji

    2006-10-01

    To assess the etiology of influenza-associated encephalopathy(IAE), a surveillance effort was conducted during 2000-2005 in Japan. Over half of fatal and handicapped IAE patients exhibited a disorder of mitochondrial beta-oxidation and ATP generation evoked by the thermolabile phenotype of carnitine palmitoyltransferase II variations with transiently elevated serum acylcarnitine during high-grade fever. Model mice having impaired mitochondrial beta-oxidation exhibited significant accumulation of mini-plasmin and up-regulation of trypsin in the cerebral capillaries after infection with influenza A virus, resulting in the destruction of blood-brain barrier and increased brain vascular permeability. Trypsin up-regulation was also evident in the neuronal cells in the hippocampus, suggesting a severe neurologic complication of IAE.

  10. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    International Nuclear Information System (INIS)

    We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

  11. Acute renal failure due to phenazopyridine (Pyridium) overdose: case report and review of the literature.

    Science.gov (United States)

    Onder, Ali Mirza; Espinoza, Veronica; Berho, Mariana E; Chandar, Jayanthi; Zilleruelo, Gaston; Abitbol, Carolyn

    2006-11-01

    Phenazopyridine (Pyridium) is a commonly used urinary tract analgesic. It has been associated with yellow skin discoloration, hemolytic anemia, methemoglobinemia, and acute renal failure, especially in patients with preexisting kidney disease. We report a 17-year-old female with vertically transmitted human immunodeficiency virus (HIV) infection, presenting with acute renal failure and methemoglobinemia following a suicidal attempt with a single 1,200 mg ingestion of Pyridium. She had no prior evidence of HIV nephropathy. The patient had a progressive nonoliguric renal failure on the 3rd day following the ingestion. She was treated with N-acetylcysteine, intravenous carnitine, and alkalinization of the urine. Her kidney biopsy revealed acute tubular necrosis with no glomerular changes. After 7 days of conservative management, she was discharged home with normal kidney function. To our knowledge, this is the second smallest amount of Pyridium overdose resulting in acute renal failure with no previous history of kidney disease. PMID:16897003

  12. [Vascular-parenchymal ratio of testes under correction of exposure to combinations of heavy metals salts].

    Science.gov (United States)

    Romaniuk, A M; Moskalenko, Iu V; Sauliak, S V; Bonchev, S D; Moskalenko, R A

    2013-06-01

    The results of the study of testes' tissue of 128 immature rats, which get within 60 days drinking water with threshold concentration of salts of copper, zinc, iron, manganese, lead, chromium. It was found that morphological changes of microvasculature was nonspecific and lead to the secondary damage of blood-testis barrier and correlated with changes in testes' parenchymal structures. Fullest possible extent of testicular parenchymal damage occurs in the areas of intensive blood supply, as well as toxic substances in these areas have a longer exposure time. Under exposure combinations of heavy metals salts of organisme the reduction of the vascular streambed in the testes is influenced by intravascular, extravascular intrawall factors. The intensity of vasculature and parenchyma violations of gland depends on duration of exposure combinations of salts of heavy metals. Applying the L-carnitine on the background of intoxication of heavy metal salts partially reduces adverse changes in testes' microvasculature streambed and parenchyma of rats. PMID:25095698

  13. Neuropathic pain treatment: still a challenge

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    Osvaldo J.M. Nascimento

    2016-06-01

    Full Text Available Neuropathic pain (NP is the result of a series of conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of NP pathophysiology previously unexplored therapies have been used with encouraging results. In this group, acetyl-L-carnitine, alpha-lipoic-acid, cannabinoids, clonidine, EMA401, botulinum toxin type A and new voltage-gated sodium channel blockers, can be included. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation. We reviewed the published literature on the pharmacological treatment of NP. Despite the interesting results, randomized controlled trials are demanded the majority of the therapies previously mentioned. In spite of several studies for the relief of NP, pain control continues being a challenge.

  14. Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism.

    Science.gov (United States)

    Elsemman, Ibrahim E; Mardinoglu, Adil; Shoaie, Saeed; Soliman, Taysir H; Nielsen, Jens

    2016-04-26

    Hepatitis C virus (HCV) infection is a worldwide healthcare problem; however, traditional treatment methods have failed to cure all patients, and HCV has developed resistance to new drugs. Systems biology-based analyses could play an important role in the holistic analysis of the impact of HCV on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular carcinoma (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin sulfate was significantly changed in the cirrhosis stage, whereas the metabolism of acyl-carnitine was significantly changed in the dysplastic nodule and early HCC stages. Our results explained the role of the upregulated expression of BCAT1, PLOD3 and six other methyltransferase genes involved in carnitine biosynthesis and S-adenosylmethionine metabolism in the early and advanced HCC stages. Moreover, GNPAT and BCAP31 expression was upregulated in the early and advanced HCC stages and could lead to increased acyl-CoA consumption. By integrating our results with copy number variation analyses, we observed that GNPAT, PPOX and five of the methyltransferase genes (ASH1L, METTL13, SMYD2, TARBP1 and SMYD3), which are all located on chromosome 1q, had increased copy numbers in the cancer samples relative to the normal samples. Finally, we confirmed our predictions with the results of metabolomics studies and proposed that inhibiting the identified targets has the potential to provide an effective treatment strategy for HCV-associated liver disorders. PMID:27040643

  15. CypD(-/-) hearts have altered levels of proteins involved in Krebs cycle, branch chain amino acid degradation and pyruvate metabolism.

    Science.gov (United States)

    Menazza, Sara; Wong, Renee; Nguyen, Tiffany; Wang, Guanghui; Gucek, Marjan; Murphy, Elizabeth

    2013-03-01

    Cyclophilin D (CypD) is a mitochondrial chaperone that has been shown to regulate the mitochondrial permeability transition pore (MPTP). MPTP opening is a major determinant of mitochondrial dysfunction and cardiomyocyte death during ischemia/reperfusion (I/R) injury. Mice lacking CypD have been widely used to study regulation of the MPTP, and it has been shown recently that genetic depletion of CypD correlates with elevated levels of mitochondrial Ca(2+). The present study aimed to characterize the metabolic changes in CypD(-/-) hearts. Initially, we used a proteomics approach to examine protein changes in CypD(-/-) mice. Using pathway analysis, we found that CypD(-/-) hearts have alterations in branched chain amino acid metabolism, pyruvate metabolism and the Krebs cycle. We tested whether these metabolic changes were due to inhibition of electron transfer from these metabolic pathways into the electron transport chain. As we found decreased levels of succinate dehydrogenase and electron transfer flavoprotein in the proteomics analysis, we examined whether activities of these enzymes might be altered. However, we found no alterations in their activities. The proteomics study also showed a 23% decrease in carnitine-palmitoyltransferase 1 (CPT1), which prompted us to perform a metabolomics analysis. Consistent with the decrease in CPT1, we found a significant decrease in C4/Ci4, C5-OH/C3-DC, C12:1, C14:1, C16:1, and C20:3 acyl carnitines in hearts from CypD(-/-) mice. In summary, CypD(-/-) hearts exhibit changes in many metabolic pathways and caution should be used when interpreting results from these mice as due solely to inhibition of the MPTP.

  16. AB229. Effect of berberine on human sperm parameters in vitro

    Science.gov (United States)

    Chen, Liping; Wang, Tao; Liu, Jihong

    2016-01-01

    Objective Berberine is a natural compound isolated from plants with multiple pharmacological activities, like antioxidant and anti-inflammatory activities. The present study was to assess the effect of berberine with different concentration and at different time on sperm motility, viability and sperm membrane integrity of humans. Methods Semen samples were obtained from 30 patients (22–30 years of age) enrolled in this study, 15 of which were normospermic and 15 were asthenozoospermic. Semen were aseptically obtained by masturbation and prepared by swim-up method. After that they were incubated in Ham’s F-10 medium for 30 min at 37 °C to mimic the temperature inside the female reproductive tract. Semen samples were divided into aliquots. The negative control condition was supplemented with no drugs while 0.4 mmol/L L-carnitine was used as positive control condition. The treatment condition was supplemented with berberine at a concentration of 10-4, 10-5, 10-6, 10-7 mol/L. Measurements of sperm viability and motility were carried out at 10, 30, 60 and 120 min after incubation in all semen samples by computer-assisted sperm analysis (CASA). Results It showed that in both normal and asthenozoospermic samples, total and progressive sperm motility were maintained by in vitro treatment with berberine, whereas a significant decrease of these parameters occurred in parallel samples incubated in medium alone. Berberine also prevented the decrease of sperm kinetics but such an effect was highly significant only in asthenozoospermic samples. Moreover, berberine had similar effort as L-carnitine even at low concentration. Conclusions In vitro, berberine with suitable concentration exerted a direct protective effect on human sperm viability, motility rate and could modify plasma membrane functional integrity, especially in the asthenozoospermic patients. This could be a novel therapeutic drug for improving the function of sperm in vitro and treatment for male infertility.

  17. SREBP-1c Gene Silencing can Decrease Lipid Deposits in Bovine Hepatocytes Cultured in Vitro

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    Qinghua Deng

    2014-05-01

    Full Text Available Background: Fatty liver is a major metabolic disorder that occurs during early lactation in high-producing dairy cows. Sterol regulatory element-binding protein-1c (SREBP-1c is an important transcription factor that regulates lipid synthesis by regulating the expression of lipid metabolism genes. Methods: In this study, we reduced the expression of SREBP-1c by adenovirus-mediated SREBP-1c with a low expression vector (AD-GFP-SREBP-1c to study the effects of SREBP-1c on lipid deposits in bovine hepatocytes. The expression levels and enzyme activities of SERBP-1c and its target genes were determined by real-time PCR, western blot, and ELISA. Results: These results showed that Ad-GFP-SREBP-1c could inhibit SREBP-1c expression. The expression of the lipid synthesis enzyme acetyl-CoA carboxylase (ACC was down-regulated. The expression levels of the lipid oxidation enzymes long-chain fatty acyl-COA synthetase (ACSL-1, carnitine palmitoyltransferase І (CPT-І, carnitine palmitoyltransferase II (CPT- II, and β-hydroxyacyl-CoA-DH (HADH were significantly elevated. Furthermore, the expression levels of factors involved in the assembly and transport of very low-density lipoproteins (VLDLs, such as apolipoprotein B100 (ApoB, apolipoprotein E (ApoE, and microsomal triglyceride transfer protein (MTTP were decreased comparison with the negative control and the blank control groups, but the low-density lipoprotein receptor (LDLR was elevated. The concentrations of TG (triglyceride and VLDL were also reduced. Conclusion: These data suggest that low SREBP-1c expression can decrease lipid synthesis, increase lipid oxidation, and decrease the TG and VLDL content in bovine hepatocytes.

  18. Evaluation of the satiating properties of a nutraceutical product containing Garcinia cambogia and Ascophyllum nodosum extracts in healthy volunteers.

    Science.gov (United States)

    Mayer, Marcos A; Finlayson, Graham; Fischman, Daniela; de Paz, Carolina; Telleriarte, Martín R; Ferrero, Alejandro J; Bobillo, Cecilia; Fernández, Belisario E

    2014-04-01

    A nutraceutical product composed of a combination of Garcinia cambogia, l-carnitine and a seaweed extract of Ascophyllum nodosum has been recently developed. The aim of the present study was to characterize its effects on subjective satiety sensations and food preferences in healthy volunteers. In a crossover design, 28 subjects (21 females and 7 males, aged 31 ± 5, BMI 22.6 ± 1.7) were randomly assigned to receive the active treatment (LIS) or placebo (PL) over one week. At the end of each treatment period, subjects were instructed to consume ad libitum a test meal. Food preferences and appetite sensations were evaluated by means of the Leeds Food Preferences Questionnaire and visual analog scales, before and after meal, over three hours. There were no differences in energy intake between study groups. LIS was associated with a reduction in subjective hunger sensations (p = 0.018) and to an increase in satiety (p = 0.02) and fullness (p = 0.01) ratings. The preference for high fat foods was reduced after consuming the test meal in both study groups. There was a significant effect of LIS treatment on food explicit liking and implicit wanting, as evidenced by an increase in preference for sweet foods (relative to savory foods; p = 0.03 and p = 0.004, respectively), but no differences were observed regarding the preference for low or high fat foods (NS). These results provide proof of principle for the satiating properties of a nutraceutical containing Garcinia cambogia, Ascophyllum nodosum extract and l-carnitine and suggest that it might be useful as an appetite modulator. PMID:24563084

  19. [Toward a more rational field-genetic epidemiology].

    Science.gov (United States)

    Koizumi, Akio

    2010-01-01

    Genetic dissection of diseases is one of the epoch-making achievements in modern medicine. Positional cloning is a key method to isolate disease-related genes. For positional cloning, there are two conventional methods: family-based studies and case-control studies. In this review, I would like to describe several family-based studies on single gene diseases which I had conducted including those of Akita diabetic mice, systemic carnitine deficiency and Hartnup disease. The study of systemic carnitine deficiency underscored a potential power of the "Carrier state." Furthermore, cultural and public health practices in Japan such as preservation of umbilical cords and mother and child passbooks enabled us to conduct linkage analysis even 20 years after the deaths of affected patients in Hartnup disease. For multifactorial diseases, I present three family-based studies: intracranial aneurysm, moyamoya and arteriovenous malformation. Finally, I discuss on theoretical issues concerning the relationship among odds ratio, phenocopy rate and penetrance by formulating a single-locus dominant association model. Analysis of the model predicted a notion that a large odds ratio facilitates familial clustering of multifactorial diseases and vice versa is the case. Furthermore, the analysis predicted that genetic markers for screening should have odds ratio >/= eight to maintain similar qualities commonly required for clinical tests. Collectively, the analysis predicted a two-stage study design composed of linkage analysis based on a family study and subsequent replication by a case-control association study is more rational than the currently used two-independent case-control design. This newly proposed method is expected to provide polymorphisms, which have large odds ratios, requiring only minimum research budgets. PMID:20134107

  20. The effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR on fatty acid oxidation in hepatocytes isolated from neonatal piglets

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    Xi Lin

    2012-10-01

    Full Text Available Abstract In the present study, the effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR on long-chain fatty acid oxidation by hepatocytes isolated from suckled neonatal pig liver (a low ketogenic and lipogenic tissue was tested. Incubation of hepatocytes with AICAR (0.5 mM in the presence of 1 mM of carnitine and 10 mM of glucose for 1 hour at 37°C had no significant effect on total [1-14C]-palmitate (0.5 mM oxidation (14CO2 and 14C-Acid soluble products (ASP. Consistent with the fatty acid oxidation, carnitine palmitoyltransferase I activity and inhibition of its activity by malonyl-CoA (10 μM assayed in cell homogenate also remained constant. However, addition of AICAR to the hepatocytes decreased 14CO2 production by 18% compared to control (p 2 caused a significant difference in distribution of oxidative products between 14CO2 and 14C-ASP (p 14C-ASP. Addition of insulin to hepatocyte incubations with AICAR did not change the oxidative product distribution between CO2 and ASP, but further promoted ACC activity. The increased ACC activity was 70% higher than in the control group when citrate was absent in the reaction medium and was 30% higher when citrate was present in the medium. Our results suggest that AICAR may affect the distribution of metabolic products from fatty acid oxidation by changing ACC activity in hepatocyte isolated from suckled neonatal piglets; however, the basis for the increase in ACC activity elicited by AICAR is not apparent.