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Sample records for carnitine

  1. Carnitine Deficiency and Pregnancy

    OpenAIRE

    Anouk de Bruyn; Yves Jacquemyn; Kristof Kinget; François Eyskens

    2015-01-01

    We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, su...

  2. Carnitine in parenteral nutrition.

    Science.gov (United States)

    Borum, Peggy R

    2009-11-01

    Several new functions or metabolic uses of carnitine and improvements in assessment of carnitine status impact carnitine dosing recommendations. Carnitine dosing will likely be customized for patients at different stages of the life cycle and for patients with dysfunction of different organs. Nutrition supplementation of carnitine should be 2-5 mg x kg(-1) x day(-1) and be administrated via the route used for administration of macronutrients. Pharmacologic supplementation of carnitine should be 50-100 mg x kg(-1) x day(-1) and be reserved for the removal of toxic compounds from the body.

  3. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn

    2015-01-01

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

  4. Carnitine and physical exercise.

    Science.gov (United States)

    Heinonen, O J

    1996-08-01

    Carnitine plays a central role in fatty acid (FA) metabolism. It transports long-chain fatty acids into mitochondria for beta-oxidation. Carnitine also modulates the metabolism of coenzyme-A (CoA). It is not surprising that the use of supplementary carnitine to improve physical performance has become widespread in recent years, although there is no unequivocal support to this practice. However, critical reflections and current scientific-based knowledge are important because the implications of reduced or increased carnitine concentrations in vivo are not thoroughly understood. Several rationales have been forwarded in support of the potential ergogenic effects of oral carnitine supplementation. However, the following arguments derived from established scientific observations may be forwarded: (i) carnitine supplementation neither enhances FA oxidation in vivo or spares glycogen or postpones fatigue during exercise. Carnitine supplementation does not unequivocally improve performance of athletes; (ii) carnitine supplementation does not reduce body fat or help to lose weight; (iii) in vivo pyruvate dehydrogenase complex (PDC) is fully active already after a few seconds of intense exercise. Carnitine supplementation induces no further activation of PDC in vivo; (iv) despite an increased acetyl-CoA/free CoA ratio, PDC is not depressed during exercise in vivo and therefore supplementary carnitine has no effect on lactate accumulation; (v) carnitine supplementation per se does not affect the maximal oxygen uptake (VO2max); (vi) during exercise there is a redistribution of free carnitine and acylcarnitines in the muscle but there is no loss of total carnitine. Athletes are not at risk for carnitine deficiency and do not have an increased need for carnitine. Although there are some theoretical points favouring potential ergogenic effects of carnitine supplementation, there is currently no scientific basis for healthy individuals or athletes to use carnitine

  5. Carnitine in neonatal nutrition.

    Science.gov (United States)

    Borum, P R

    1995-11-01

    Experimental evidence from several investigators suggests that carnitine is a conditionally essential nutrient for neonates. If carnitine is a conditionally essential nutrient for the neonate, most neonates on total parenteral nutrition in the United States are not receiving adequate nutritional support. The metabolic functions of carnitine are varied and important in several aspects of neonatal physiology. All neonates receiving breast milk receive dietary carnitine and most neonates receiving enteral infant formulas receive dietary carnitine at a level similar to that of the breast-fed neonate. However, most neonates on total parenteral nutrition receive no dietary carnitine. Investigators have been testing the working hypothesis that carnitine is a conditionally essential nutrient for the neonate for many years. This review discusses (1) data supporting the hypothesis, (2) reasons why it has not been either proved or disproved by now, and (3) the author's view of a prudent approach to dietary carnitine supplementation of neonates.

  6. 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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

  9. Role of carnitine in disease

    OpenAIRE

    Flanagan Judith L; Simmons Peter A; Vehige Joseph; Willcox Mark DP; Garrett Qian

    2010-01-01

    Abstract Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, en...

  10. 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

  11. Risk assessment for carnitine.

    Science.gov (United States)

    Hathcock, John N; Shao, Andrew

    2006-10-01

    Carnitine is a conditionally essential amino acid-like compound involved in the transport of long-chain fatty acids into the mitochondria during the beta-oxidation process. Carnitine has become an increasingly popular ingredient in dietary supplements, especially weight loss and some sports nutrition products. A number of clinical trials have been conducted examining the effect of carnitine supplementation on weight loss and energy balance. Regarding safety, systematic evaluation of the research designs and data do not provide a basis for risk assessment and the usual safe upper level of intake (UL) derived from it unless the newer methods described as the observed safe level (OSL) or highest observed intake (HOI) are utilized. The OSL risk assessment method indicates that the evidence of safety is strong at intakes up to 2000mg/day l-carnitine equivalents for chronic supplementation, and this level is identified as the OSL. Although much higher levels have been tested without adverse effects and may be safe, the data for intakes above 2000mg/day are not sufficient for a confident conclusion of long-term safety.

  12. Role of carnitine in disease

    Directory of Open Access Journals (Sweden)

    Flanagan Judith L

    2010-04-01

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

  13. [Catabolism of carnitine: products of carnitine decarboxylase and carnitine dehydrogenase in vivo].

    Science.gov (United States)

    Seim, H; Löster, H; Strack, E

    1980-09-01

    1) Rats and mice were given large oral or subcutaneous doses of (-)-L-, (+)-D- and DL-carnitine (5 mg/g body weight). The carnitine metabolites, beta-methylcholine and acetonyltrimethylammonium, were isolated from the urine by special methods, and determined as their characteristic derivatives (2,4-dinitrophenylhydrazone and butyric ester) by thin-layer chromatography or photometry. 2) beta-Methylcholine, the product of carnitine decarboxylase, was not excreted, even when animals were heavily dosed with both carnitine isomers, with or without starvation. 3) After the administration of (+)-D- and DL-carnitine, both species excreted acetonyltrimethylammonium, which is already known as the spontaneous decarboxylation product of dehydrocarnitine (product of carnitine dehydrogenase) in bacteria. Injection of 0.71 mmol (+)-D-carnitine resulted in the excretion of 5.0 mumol (average) acetonyltrimethylammonium per mouse during the 48 h post injection. Under the same conditions, rats produced up to 40 mumol acetonyltrimethylammonium. The ratio of excreted acetonyltrimethylammonium to injected (+)-D-carnitine depended on the method of administration and the dose. 4) Production of the pharmacologically active (+)-acetyl-L-beta-methylcholine is not to be expected, following high exogenous doses of (-)-L-carnitine or (-)-acetyl-L-carnitine. The chief metabolites are trimethylamine, trimethylamine oxide and gamma-butyrobetaine (this journal 361, 1059), and both the (-)-L-carnitine pool and exogenous (-)-L-carnitine are dehydrogenated or decarboxylated only to a very small extent, if at all. When DL-carnitine is used therapeutically, the formation of acetonyltrimethylammonium must be taken into account.

  14. Enzymology of the carnitine biosynthesis pathway.

    Science.gov (United States)

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

    2010-05-01

    The water-soluble zwitterion carnitine is an essential metabolite in eukaryotes required for fatty acid oxidation as it functions as a carrier during transfer of activated acyl and acetyl groups across intracellular membranes. Most eukaryotes are able to synthesize carnitine endogenously, besides their capacity to take up carnitine from the diet or extracellular medium through plasma membrane transporters. This review discusses the current knowledge on carnitine homeostasis with special emphasis on the enzymology of the four steps of the carnitine biosynthesis pathway.

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

    OpenAIRE

    Nakamura, Masaru; Nagamine, Takahiko

    2015-01-01

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

  16. 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.

  17. The use of carnitine in pediatric nutrition.

    Science.gov (United States)

    Crill, Catherine M; Helms, Richard A

    2007-04-01

    Carnitine is synthesized endogenously from methionine and lysine in the liver and kidney and is available exogenously from a meat and dairy diet and from human milk and most enteral formulas. Parenteral nutrition (PN) does not contain carnitine unless it is extemporaneously added. The primary role of carnitine is to transport long-chain fatty acids across the mitochondrial membrane, where they undergo beta-oxidation to produce energy. Although the majority of patients are capable of endogenous synthesis of carnitine, certain pediatric populations, specifically neonates and infants, have decreased biosynthetic capacity and are at risk of developing carnitine deficiency, particularly when receiving PN. Studies have evaluated for several decades the effects of carnitine supplementation in pediatric patients receiving nutrition support. Early studies focused primarily on the effects of supplementation on markers of fatty acid metabolism and nutrition markers, including weight gain and nitrogen balance, whereas more recent studies have evaluated neonatal morbidity. This review describes the role of carnitine in metabolic processes, its biosynthesis, and carnitine deficiency syndromes, as well as reviews the literature on carnitine supplementation in pediatric nutrition.

  18. Carnitine Level Changes with the Ketogenic Diet

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-01-01

    Full Text Available The effects of the ketogenic diet (KD on carnitine levels were determined in 38 consecutive patients with epilepsy treated at Rush-Presbyterian-St Luke’s Medical Center, Chicago, IL Carnitine levels were determined at 0, 1, 6, 12, and 24 months of diet treatment.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    Ronald J.A. Wanders

    2016-07-01

    Full Text Available Carnitine, essential for fatty acid β-oxidation, is obtained from diet and through de novo biosynthesis. The organic cation/carnitine transporter 2 (OCTN2 facilitates carnitine cellular transport and kidney resorption. Carnitine depletion occurs in OCTN2-deficient patients, with serious clinical complications including cardiomyopathy, myopathy, and hypoketotic hypoglycaemia. Neonatal screening can detect OCTN2 deficiency. OCTN2-deficiency is also known as primary carnitine deficiency. Carnitine deficiency may result from fatty acid β-oxidation disorders, which are diagnosed via plasma acylcarnitine profiling, but also under other conditions including haemodialysis. Given the importance of the kidney in maintaining carnitine homeostasis, it is not unexpected that longterm haemodialysis treatment is associated with the development of secondary carnitine deficiency, characterised by low endogenous L-carnitine levels and accumulation of deleterious medium and long- chain acylcarnitines. These alterations in carnitine pool composition have been implicated in a number of dialysis-related disorders, including erythropoietin-resistant renal anaemia. The association between erythropoietin resistance and carnitine levels has been demonstrated, with the proportion of medium and long-chain acylcarnitines within the total plasma carnitine pool positively correlated with erythropoietin resistance. Recent research has demonstrated that carnitine supplementation results in a significant reduction in erythropoietin dose requirements in patients with erythropoietin-resistant anaemia. Few studies have been conducted assessing the treatment of carnitine deficiency and haemodialysisrelated cardiac complications, particularly in children. Thus, a study was recently conducted which showed that intravenous carnitine in children receiving haemodialysis significantly increased plasma carnitine.

  1. Carnitine and total parenteral nutrition of the neonate.

    Science.gov (United States)

    Schmidt-Sommerfeld, E; Penn, D

    1990-01-01

    The newborn is dependent upon fat for energy production. Fatty acid oxidation requires the cofactor carnitine. The preterm infant is born with limited carnitine reserves. During total parenteral nutrition (TPN) plasma and tissue carnitine concentrations decrease indicating that rates of carnitine biosynthesis are inadequate. The ability of the premature infant to oxidize fatty acids is related to the carnitine status. Several studies suggest an improvement of fatty acid oxidation after a fat challenge if TPN is supplemented with L-carnitine. Nitrogen balance may also be improved but this needs confirmation. It remains to be established whether routine L-carnitine supplementation is needed in neonatal TPN.

  2. Carnitine deficiency in surgical neonates receiving total parenteral nutrition.

    Science.gov (United States)

    Tibboel, D; Delemarre, F M; Przyrembel, H; Bos, A P; Affourtit, M J; Molenaar, J C

    1990-04-01

    Carnitine plays a key role in the oxidation of fatty acids. Most solutions for parenteral nutrition do not contain carnitine. Because endogenous carnitine synthesis is insufficient in newborns, they are prone to developing a carnitine deficiency when they are dependent on total parenteral nutrition (TPN). Stimulated by the clinical observation of manifest clinical symptoms of carnitine deficiency in one patient, a study of 13 consecutive neonates who received TPN for over 2 weeks was begun. Their plasma carnitine levels before and during carnitine supplementation were determined. All patients had a carnitine intake far below the recommended minimal need of 11 mumol/kg per day. Although only three of them clearly showed clinical symptoms described as carnitine deficiency, carnitine supplementation for all neonates receiving TPN for over 2 weeks is recommended.

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

    OpenAIRE

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

    2016-01-01

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

  4. Primary and secondary alterations of neonatal carnitine metabolism.

    Science.gov (United States)

    Scaglia, F; Longo, N

    1999-04-01

    Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane, in the detoxification of acyl moieties, and in maintaining normal levels of free coenzyme A. Although carnitine can be synthesized in liver and kidney, normal adults obtain the majority of carnitine from the diet. Preterm newborns have a reduced capacity to synthesize carnitine. Total parenteral nutrition lacks carnitine and exposes very low birth weight infants to carnitine deficiency, with decreased production of ketones from long-chain fatty acids. Supplementation with low doses of carnitine improves nitrogen balance and growth in these infants. Carnitine deficiency can be part of a number of inherited and acquired diseases. Primary carnitine deficiency is an autosomal recessive disorder characterized by increased losses of carnitine in the urine and decreased accumulation in the heart and skeletal muscle caused by defective carnitine transport. This condition is corrected by high-dose carnitine supplementation. Secondary carnitine deficiency can be caused by increased losses, pharmacological therapy, or a number of inherited metabolic disorders that must be correctly diagnosed before initiating carnitine supplementation.

  5. Carnitine balance and effects of intravenous L-carnitine in two patients receiving long-term total parenteral nutrition.

    Science.gov (United States)

    Worthley, L I; Fishlock, R C; Snoswell, A M

    1984-01-01

    Two patients requiring total parenteral nutrition for 34 and 39 months, had plasma and urinary carnitine assays and plasma lipid assays performed before and during intravenous administration of 400 mg (2500 mumol) of L-carnitine for 7 days, followed by 40 mg (240 mumol) daily continuously. One patient had generalized lethargy and weakness which resolved within the first 5 days of carnitine administration. The plasma-free carnitine levels in this patient rose significantly. The other patient was asymptomatic and while there was no significant change in the plasma-free carnitine levels during carnitine administration, this patient remained in positive carnitine balance throughout the study. There were no significant changes in plasma lipid levels in either patient. In adult patients requiring long-term total parenteral nutrition who are otherwise normal, intravenous L-carnitine may be required to supplement the patients endogenous carnitine production.

  6. Genetics Home Reference: carnitine palmitoyltransferase I deficiency

    Science.gov (United States)

    ... G, Lillquist Y, Wanders RJ, Olpin SE. The paradox of the carnitine palmitoyltransferase type Ia P479L variant ... Support Selection Criteria for Links USA.gov Copyright Privacy Accessibility FOIA Viewers & Players U.S. Department of Health & ...

  7. Genetics Home Reference: primary carnitine deficiency

    Science.gov (United States)

    ... Majdalani M. Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype. Clin Genet. 2014 Feb; ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  8. Carnitine palmitoyltransferase 2 deficiency: the time-course of blood and urinary acylcarnitine levels during initial L-carnitine supplementation.

    Science.gov (United States)

    Hori, Tomohiro; Fukao, Toshiyuki; Kobayashi, Hironori; Teramoto, Takahide; Takayanagi, Masaki; Hasegawa, Yuki; Yasuno, Tetsuhiko; Yamaguchi, Seiji; Kondo, Naomi

    2010-07-01

    Carnitine palmitoyltransferase 2 (CPT2) deficiency is one of the most common mitochondrial beta-oxidation defects. A female patient with an infantile form of CPT2 deficiency first presented as having a Reye-like syndrome with hypoglycemic convulsions. Oral L-carnitine supplementation was administered since serum free carnitine level was very low (less than 10 micromol/L), indicating secondary carnitine deficiency. Her serum and urinary acylcarnitine profiles were analyzed successively to evaluate time-course effects of L-carnitine supplementation. After the first two days of L-carnitine supplementation, the serum level of free carnitine was elevated; however, the serum levels of acylcarnitines and the urinary excretion of both free carnitine and acylcarnitines remained low. A peak of the serum free carnitine level was detected on day 5, followed by a peak of acetylcarnitine on day 7, and peaks of long-chain acylcarnitines, such as C16, C18, C18:1 and C18:2 carnitines, on day 9. Thereafter free carnitine became predominant again. These peaks of the serum levels corresponded to urinary excretion peaks of free carnitine, acetylcarnitine, and medium-chain dicarboxylic carnitines, respectively. It took several days for oral L-carnitine administration to increase the serum carnitine levels, probably because the intracellular stores were depleted. Thereafter, the administration increased the excretion of abnormal acylcarnitines, some of which had accumulated within the tissues. The excretion of medium-chain dicarboxylic carnitines dramatically decreased on day 13, suggesting improvement of tissue acylcarnitine accumulation. These time-course changes in blood and urinary acylcarnitine levels after L-carnitine supplementation support the effectiveness of L-carnitine supplementation to CPT2-deficient patients.

  9. Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation.

    Science.gov (United States)

    Schmidt-Sommerfeld, E; Penn, D; Wolf, H

    1983-06-01

    To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.

  10. Carnitine deficiency in premature infants receiving total parenteral nutrition.

    Science.gov (United States)

    Penn, D; Schmidt-Sommerfeld, E; Wolf, H

    1980-03-01

    Carnitine plays a significant role in fatty acid utilization and ketone body production. Its availability is especially important during the immediate postnatal period. To determine whether low birth weight infants who cannot be orally fed are at risk of developing carnitine deficiency, we compared the carnitine blood levels and urinary excretion of 12 premature infants (Group A) receiving total parenteral nutrition (TPN) with those of 8 infants of similar gestational age and birth weight (Group B) who received carnitine-containing milk formulas. In Group A, serum levels of total and free carnitine fell after 5 days of carnitine-deficient parenteral nutrition, and urinary excretion was significantly reduced. Serum levels and urinary excretion increased after the onset of oral feedings. The control Group B exhibited no significant changes in carnitine blood levels between the first and fifth days of life, but did show a later increase. Children in Group A had lower carnitine blood levels compared to those in Group B on the fifth day of life. These findings suggest that premature infants are not able to synthesize enough carnitine to maintain blood levels, and that carnitine deficiency can occur following TPN. Further investigation of metabolic consequences secondary to deficient carnitine intake in premature infants is necessary before carnitine supplementation should be considered.

  11. Effect of (L-Carnitine) on acetyl-L-carnitine production by heart mitochondria

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-05-01

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

  12. Carnitine treatment for stroke in rats.

    Science.gov (United States)

    Slivka, A; Silbersweig, D; Pulsinelli, W

    1990-05-01

    Changes in the concentrations of carnitine, long-chain acylcoenzyme A, and long-chain acylcarnitine in ischemic myocardium parallel those in ischemic brain. Since carnitine treatment reverses these changes and improves function in ischemic hearts, we examined whether carnitine given to rats before focal cerebral ischemia (produced by tandem right common carotid artery and middle cerebral artery occlusion) alters infarct volume in four separate experiments. Mannitol was used to control for the osmotic effect of carnitine on brain edema in one experiment. While carnitine was found to significantly decrease infarct volume compared with saline in one experiment (p less than 0.05, Student's t test), this result could not be replicated in the subsequent three experiments. Because the positive treatment effect was not reproducible despite similar experimental conditions, the result of the first experiment was attributed to a type I error. Mannitol also showed no significant effect on infarct volume. This study emphasizes the need for concurrent controls with each group of treated animals and the need for replicating the results of a single experiment when testing for drug efficacy in animal models of focal cerebral ischemia.

  13. 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...

  14. Primary Carnitine deficiency in the Faroe Islands

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... apart from left ventricular hypertrophy with normal systolic function in one young male. Symptoms, e.g. fatigue, were reported in 43 % with a reduction to 12 % (p carnitine supplementation. Eighty two % reported participation in sports of which 52 % were...

  15. The effect of carnitine on ketogenesis in perfused livers from juvenile visceral steatosis mice with systemic carnitine deficiency.

    Science.gov (United States)

    Nakajima, T; Horiuchi, M; Yamanaka, H; Kizaki, Z; Inoue, F; Kodo, N; Kinugasa, A; Saheki, T; Sawada, T

    1997-07-01

    Juvenile visceral steatosis (JVS) mice have been reported to have systemic carnitine deficiency, and the carnitine concentration in the liver of JVS mice was markedly lower than that of controls (11.6 +/- 2.6 versus 393.5 +/- 56.4 nmol/g of wet liver). To evaluate the role of carnitine in mitochondrial beta-oxidation in liver, we examined the effects of carnitine on ketogenesis in perfused liver from control and JVS mice. In control mice, ketogenesis was increased by the infusion of 0.3 mM oleate, but not by L-carnitine. In contrast, although ketogenesis in JVS mice was not increased by the infusion of oleate, it was increased 2.5-fold by the addition of 1000 microM L-carnitine. Addition of 50, 100, and 200 microM L-carnitine increased ketogenesis in a dose-dependent manner. The infusion of 0.3 mM octanoate or butyrate increased ketogenesis in a carnitine-independent fashion in both control and JVS mice. These findings suggest that endogenous long chain fatty acids from accumulated triglycerides may be used as substrates in the presence of carnitine in JVS mice. The relationship between ketogenesis and free carnitine concentration was examined in livers from JVS mice. Ketogenesis increased as free carnitine levels increased until concentrations exceeded about 100 nmol/g of wet liver (340 microM). The free carnitine concentration required for half-maximal ketone body production in liver of JVS mice was 45 microM (13 nmol/g of wet liver), which corresponds to a K(m) value of carnitine palmitoyltransferase I. We conclude that carnitine is a rate-limiting factor for beta-oxidation in liver only when the carnitine level in liver is very low.

  16. L-carnitine--metabolic functions and meaning in humans life.

    Science.gov (United States)

    Pekala, Jolanta; Patkowska-Sokoła, Bozena; Bodkowski, Robert; Jamroz, Dorota; Nowakowski, Piotr; Lochyński, Stanisław; Librowski, Tadeusz

    2011-09-01

    L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects.

  17. Carnitine ester excretion in pediatric patients receiving parenteral nutrition.

    Science.gov (United States)

    Schmidt-Sommerfeld, E; Penn, D; Bieber, L L; Kerner, J; Rossi, T M; Lebenthal, E

    1990-08-01

    Carnitine plasma concentrations and the excretion of carnitine and individual carnitine esters were determined in 25 children and adolescents with gastrointestinal diseases receiving carnitine-free parenteral nutrition for at least 1 mo using radiochemical and radioisotopic exchange HPLC methods. Children less than 12-y-old usually had carnitine plasma concentrations less than -2 SD from the normal mean for age, whereas patients greater than 12-y-old had carnitine plasma concentrations within the normal range. Age was the only variable to correlate significantly with plasma carnitine concentrations during parenteral nutrition. Free carnitine (FC) excretion was closely correlated with plasma FC concentrations and minimal at values less than 25 mumols/L. The excretion of FC and short-chain acylcarnitines was reduced by an order of magnitude in younger compared with older patients and controls, but the excretion of "other" acylcarnitines was less affected. Some of the latter were tentatively identified using gas-liquid chromatographic and mass spectroscopic techniques as unsaturated and/or branched medium-chain carnitine esters with a carbon chain of C8-C10. The results suggest that FC and short-chain acylcarnitine are conserved by the kidney in nutritional carnitine deficiency but that there may be an obligatory renal excretion of other carnitine esters that contributes to the development of hypocarnitinemia in the younger age group.

  18. Urinary carnitine excretion in surgical patients on total parenteral nutrition.

    Science.gov (United States)

    Tanphaichitr, V; Lerdvuthisopon, N

    1981-01-01

    Urinary free and total carnitine excretions were measured in 41 normal adults and seven surgical patients on fat-free total parenteral nutrition for 8 to 45 days. The means (+/-SEM) of urinary free and total carnitine excretion in normal adults were 162 +/- 19 and 328 +/- 28 micrometers/days, respectively. All of the patients exhibited protein-calorie malnutrition with a mean carnitine intake of 11.6 +/- 1.5 micrometers/day. Under this stringent carnitine economy with the adequate supply of lysine and methionine, urinary total carnitine excretion significantly reduced to 127 to 162 micrometers/day. This probably reflects the carnitine biosynthetic rate. However, during the periods of operation and/or infection, urinary total carnitine excretion significantly increased 2- to 7-fold that of normal levels. Significant positive correlation was found between the two forms of urinary carnitine and total nitrogen excretions. Serum free and total carnitine levels in patients were significantly higher than normal adults. Such findings can be explained by the endocrine responses to the stress phenomenon and indicate a catabolic response of skeletal muscle in which most of the body carnitine resides. This can impair their carnitine status.

  19. Increased plasma carnitine concentrations in preeclampsia

    NARCIS (Netherlands)

    Thiele, IGI; Niezen-Koning, KE; van Gennip, AH; Aarnoudse, JG

    2004-01-01

    OBJECTIVE: Preeclampsia is associated with abnormal lipid metabolism, including fatty acid metabolism. Carnitine plays an indispensable role in the oxidation of fatty acids. The aim of the study was to evaluate the possible role of abnormal fatty add oxidation in preeclampsia by comparing plasma car

  20. Effect of carnitine on lipid metabolism in the neonate. II. Carnitine addition to lipid infusion during prolonged total parenteral nutrition.

    Science.gov (United States)

    Orzali, A; Maetzke, G; Donzelli, F; Rubaltelli, F F

    1984-03-01

    The effect of carnitine administration on lipid metabolism and carnitine and acylcarnitine plasma values of newborn infants, given total parenteral nutrition for the first 7 days of life, was studied during a 4-hour infusion of Intralipid. An increase in plasma concentrations of total carnitine, free carnitine, and short-chain and long-chain acylcarnitine was found, but no significant change in triglycerides, free fatty acids, glycerol, or beta-hydroxybutyrate plasma values was noted, as compared with values obtained without carnitine administration. Moreover, the low free carnitine and short-chain and long-chain acylcarnitine plasma levels found in newborn infants after 7 days of total parenteral nutrition did not seem to impair the utilization of infused lipids. The results support the concept that the relation between the carnitine pool and lipid metabolism can be influenced by intravenous glucose infusion. Low carnitine plasma concentrations do not necessarily signify a depletion of body carnitine, and sufficient tissue carnitine concentrations can probably maintain good lipid utilization for an extended period.

  1. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis.

    Science.gov (United States)

    Tarighat Esfanjani, Ali; Mahdavi, Reza; Ebrahimi Mameghani, Mehrangiz; Talebi, Mahnaz; Nikniaz, Zeinab; Safaiyan, Abdolrasool

    2012-12-01

    Given the conflicting results about the positive effects of magnesium and L-carnitine and as there is no report concerning concurrent supplementation of magnesium and L-carnitine on migraine prophylaxis, the effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation on migraine indicators were assessed. In this clinical trial, 133 migrainous patients were randomly assigned into three intervention groups: magnesium oxide (500 mg/day), L-carnitine (500 mg/day), and Mg-L-carnitine (500 mg/day magnesium and 500 mg/day L-carnitine), and a control group. After 12 weeks of supplementation, the checklist of migraine indicators including migraine attacks/month, migraine days/month, and headache severity was completed, and serum concentrations of magnesium and L-carnitine were measured by atomic absorption spectrophotometry and enzymatic UV test, respectively. The results showed a significant reduction in all migraine indicators in all studied groups (p supplemented and control groups (p = 0.008). By separating the effects of magnesium supplementation from other confounding factors such as routine treatments using the repeated measures and nested model, it was clarified that magnesium supplementation had a significant effect on all migraine indicators. Oral supplementation with magnesium oxide and L-carnitine and concurrent supplementation of Mg-L-carnitine besides routine treatments could be effective in migraine prophylaxis; however, larger trials are needed to confirm these preliminary findings.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with L-carnitine in patients homozygous for c.95A>G. Methods: Five male patients homozygous for c.95A>G were included. Regular L-carnitine supplementation was stopped and the patients were observed during...... 38.7 (SD 20.4) to 6.3 (SD 1.7) μmol/L within 96 h (p supplementation was approximately 9 h. Renal reabsorption of filtered carnitine following oral supplementation was 23%. The level of mean free carnitine excreted in urine correlated (R (2) = 0.78, p ...C0 in plasma. Conclusion: Patients homozygous for the c.95A>G mutation demonstrated limited skeletal muscle carnitine stores despite long-term high-dosage L-carnitine supplementation. Exacerbated renal excretion resulted in a short T 1/2 in plasma carnitine following the last oral dose of L-carnitine...

  3. Supplementation with carnitine for weight loss: a biochemical approach

    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 mostlikely present in all animal species, and in numerous microorganisms and plants. Recently the trend in the field of weightcontrol is to include carnitine in the diet as an agent responsible for weight loss. In the present review, some findings arediscussed from a biochemical point of view to illustrate if the use of carnitine for weight loss can be considered fiction orreality.

  4. Supplementation with carnitine for weight loss: a biochemical approach

    OpenAIRE

    José Henry Osorio

    2011-01-01

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

  5. 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.

  6. Cardiac conduction improvement in two heterozygotes for primary carnitine deficiency on L-carnitine supplementation.

    Science.gov (United States)

    Sarafoglou, K; Tridgell, A H C; Bentler, K; Redlinger-Grosse, K; Berry, S A; Schimmenti, L A

    2010-08-01

    Expanded newborn screening (NBS) for free carnitine levels has led to the identification of a larger number of heterozygous infants of undiagnosed mothers affected with systemic primary carnitine deficiency (PCD), which in turn leads to the identification of other undiagnosed heterozygous family members. There is an increasing recognition that individuals heterozygous for mutations of genes involved in fatty acid oxidation (FAO) may become symptomatic under environmental stress (fasting, prolonged exercise and illness). Considering the importance of carnitine in FAO, its role in heart and bowel function and in lipid metabolism, what is still little known is the phenotypic variability, biochemical parameters and clinical course of PCD heterozygotes with consistently low-to-normal levels to low levels of carnitine over a lifetime. We report on three generations of a family--an asymptomatic PCD heterozygous infant identified through NBS that led to the diagnosis of her asymptomatic PCD-affected mother and the heterozygous status of the maternal grandparents who report some cardiac symptoms that overlap with PCD that improved with L-carnitine supplementation.

  7. Parenteral nutrition in preterm neonates with and without carnitine supplementation.

    Science.gov (United States)

    Larsson, L E; Olegård, R; Ljung, B M; Niklasson, A; Rubensson, A; Cederblad, G

    1990-08-01

    The effects of carnitine supplementation on fat and glucose metabolism and carnitine balance were studied in 12 preterm neonates receiving full or partial parenteral nutrition (PN) for 5 to 21 days. The gestational age ranged from 27 to 32 weeks and the birth weight from 790 to 2090 g. The neonates were assigned at random to receive either L-carnitine 10 mg/kg (n = 6) or saline (n = 6). In the carnitine group, increased concentrations in plasma of total and free carnitine were observed. Less than 50% of the given dose was recovered in urine. In the placebo group no changes in the total plasma carnitine concentration were seen. In all neonates plasma triglycerides, free fatty acids, glycerol, alanine, 3-hydroxybutyrate (BOB), glucose and lactate were measured at predetermined intervals. The only significant difference between the groups was higher BOB-concentrations in the carnitine group 2 days after the start of parenteral nutrition. Elevated BOB concentrations are an indicator of improved fatty acid oxidation in the carnitine group. In this study, only a temporary effect of the carnitine supplementation was found.

  8. Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body carnitine pool, skeletal muscle composition, and physical performance in mice

    OpenAIRE

    Morand, Réjane; Bouitbir, Jamal; Felser, Andrea; Hench, Jürgen; Handschin, Christoph; Frank, Stephan; Krähenbühl, Stephan

    2014-01-01

    Pharmacokinetics and effects on skeletal muscle and physical performance of oral acetylcarnitine and propionylcarnitine are not well characterized. We therefore investigated the influence of oral acetylcarnitine, propionylcarnitine, and carnitine on body carnitine homeostasis, energy metabolism, and physical performance in mice and compared the findings to non-supplemented control animals.; Mice were supplemented orally with 2 mmol/kg/day carnitine, acetylcarnitine, or propionylcarnitine for ...

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

    NARCIS (Netherlands)

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

    1991-01-01

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

  10. The role of carnitine in the perinatal period.

    Science.gov (United States)

    Kępka, Alina; Chojnowska, Sylwia; Okungbowa, Osazee E; Zwierz, Krzysztof

    2014-01-01

    Carnitine (2-hydroxy-4-trimethylammonium butyrate, vitamin BT) is a small hydrophilic molecule derived from protein-bound lysine, not degraded in the body but excreted via urine, bile and breast milk. Carnitine stimulates the catabolism of long-chain fatty acids (FAs), by transporting them to mitochondria for oxidation, and the intracellular decomposition of branched-chain ketoacids. It also helps to excrete toxic exogenous and nontoxic endogenous organic acids via urine. It further participates in the production of pulmonary surfactant, inhibits free radicals production and demonstrates other antioxidant properties. After delivery, infants dramatically increase energy demands for movement, growth, differentiation and maintenance of the body temperature that strongly depend on FAs oxidation which is facilitated by carnitine. At early stages of life, carnitine biosynthesis is less efficient than in adults and immature infants have less carnitine tissue reserves than term infants. Carnitine supplementation is recommended in newborns with aciduria, childhood epilepsy associated with valproate-induced hepatotoxicity, in kidney-associated syndromes, and premature infants receiving total parenteral nutrition. Concentrations of carnitine and acylcarnitines in neonatal blood have been postulated a useful tool for the diagnosis of type 1 diabetes, as well as the detection and monitoring of many inherited and acquired metabolic disorders. Taking into account the complex metabolic role of cellular FAs transporters, further studies are needed on indications and contraindications for carnitine supplementation in different clinical settings during early developmental period.

  11. Risks and benefits of carnitine supplementation in diabetes.

    Science.gov (United States)

    Dambrova, M; Liepinsh, E

    2015-02-01

    L-carnitine is a very popular food supplement due to its safety profile, antioxidant-type activity and suggested effects on energy metabolism pathways. L-carnitine participates in both fatty acid transport pathways and the export of acetyl groups out of the mitochondria. However, contradictory data exist concerning the pharmacological outcomes of L-carnitine treatment in diabetes mellitus, which is a highly prevalent metabolic disease characterised by hyperglycemia and associated with severe complications, including cardiovascular disease and dyslipidemia. Recently, the L-carnitine-derived metabolites, acylcarnitines and trimethylamine-N-oxide, have been associated with increased cardio-metabolic risks. This review aims to highlight the possible risks and benefits of L-carnitine supplementation.

  12. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Cruciani, Ricardo A; Dvorkin, Ella; Homel, Peter; Culliney, Bruce; Malamud, Stephen; Lapin, Jeanne; Portenoy, Russell K; Esteban-Cruciani, Nora

    2009-04-01

    Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (Pcarnitine during the double-blind phase

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

    OpenAIRE

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

    2014-01-01

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

  14. 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.

  15. Plasma carnitine levels in patients receiving home parenteral nutrition.

    Science.gov (United States)

    Bowyer, B A; Fleming, C R; Ilstrup, D; Nelson, J; Reek, S; Burnes, J

    1986-01-01

    Patients on long-term home parenteral nutrition (HPN) are known to frequently develop hepatic steatosis or steatohepatitis. The etiology of this steatosis or steatohepatitis is unknown, but carnitine deficiency has been one of the postulated mechanisms. The importance of L-carnitine in hepatic fatty acid oxidation and the steatosis observed in primary and acquired carnitine deficiencies prompted us to determine plasma carnitine levels in 37 patients receiving long-term HPN. Thirteen patients (35%) had low total and free plasma carnitine levels. Fifteen of the 37 HPN patients were matched for age and sex with 15 patients with Crohn's disease who did not require HPN. Mean total and free plasma carnitine values were significantly lower (p less than 0.001) in these 15 HPN patients (32.2 +/- 11.9 and 28.4 +/- 10.8) when compared to Crohn's patients not requiring HPN (49.1 +/- 10.9 and 46.4 +/- 11.5). Associations were not detected between plasma carnitine and clinical or biochemical parameters that might have explained the low values.

  16. Cardiac effects of carnitine supplementation in experimental uraemia.

    Science.gov (United States)

    Seymour, Anne-Marie; Reddy, Veena; Bhandari, Sunil

    2013-06-01

    Cardiovascular complications are the leading cause of death in patients with chronic kidney disease. The uraemic heart undergoes remodelling and changes in metabolic function. Experimental uraemia produces a reduction in the myocardial energy reserve phosphocreatine in parallel with left ventricular hypertrophy and depletion of serum carnitine. This study investigated the effects of chronic L-carnitine supplementation on myocardial substrate metabolism and function in the experimental uraemia. Experimental uraemia was induced surgically in male Sprague-Dawley rats via a subtotal nephrectomy. Carnitine was administered continuously via subcutaneous mini-osmotic pumps. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C NMR, at 3 and 6 weeks. Uraemic animals exhibited anaemia, kidney dysfunction and systemic carnitine deficiency but no myocardial tissue carnitine deficiency. Myocardial hypertrophy was abolished following carnitine supplementation. This was associated with a reduction in glucose utilisation. In summary carnitine supplementation prevents cardiac hypertrophy, and this effect is amplified with the duration of treatment. This is associated with a reduction in myocardial glucose utilisation but no significant modulation of myocardial function.

  17. The Efficacy of L-Carnitine Treatment in Dilated Cardiomyopathy

    OpenAIRE

    DÖNDER, Emir

    1998-01-01

    This study was carried out to investigate clinical effects of treatment with the supplementation of L-carnitine in cases with dilated cardiomyopathy. B Mode, M-Mode, and continuous Doppler echocardiograms were applied with standard techniques in totally 28 patients assessed before treatment with L-carnitine and at the 1 st , 5 th , 10 th , 30 th , and 60 th days of the treatment. The diameter of the left ventricular endsystolic and end-diastolic have decreased with L-carnitine tre...

  18. Metabolic effects induced by L-carnitine and propionyl-L-carnitine in human hypoxic muscle tissue during exercise.

    Science.gov (United States)

    Corbucci, G G; Montanari, G; Mancinelli, G; D'Iddio, S

    1990-01-01

    An experimental model was developed to investigate some metabolic effects of strenuous exercise in hypoxic muscle tissue of human volunteers. The incidence of carnitine supplementation was studied, assuming as marker the thiobarbituric acid reaction products analysed in plasma samples collected during the course of the protocol programme. Propionyl-L-carnitine appears to antagonize in a significant degree the damaging effects of muscle fatigue combined with hypoxic status. Under these conditions the detoxifying role played by propionyl-L-carnitine, previously reported in various tissues and in other pathological conditions, appears to be relevant, although further studies are needed to elucidate the pharmacodynamics of this molecule.

  19. 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.

  20. Increased plasma carnitine in trauma patients given lipid-supplemented total parenteral nutrition.

    Science.gov (United States)

    Davis, A T; Albrecht, R M; Scholten, D J; Morgan, R E

    1988-12-01

    The purpose of this study was to determine the effects of altering the fuel substrate mix of total parenteral nutrition (TPN) on plasma and urinary carnitine in trauma patients. TPN solutions were either 100% carbohydrate (CHO) based or lipid based (70% CHO, 30% lipid). There were statistically significant (p less than 0.05) increases in plasma levels of free carnitine, short-chain acyl carnitine, and total carnitine in trauma patients receiving lipid-based TPN. No significant differences in urinary carnitine excretion were noted between groups. We conclude that the use of lipids in the TPN of trauma patients leads to an alteration in plasma carnitine metabolism.

  1. 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

  2. l-carnitine and cancer cachexia: Clinical and experimental aspects

    OpenAIRE

    Silvério, Renata; Laviano, Alessandro; Rossi Fanelli, Filippo; Seelaender, Marília

    2011-01-01

    Cancer cachexia is a multifaceted syndrome characterized, among many symptoms, by extensive muscle wasting. Chronic systemic inflammation, partly triggered and sustained by cytokines, as well as increased oxidative stress contributes to the pathogenesis of this complex metabolic disorder. l-carnitine plays a central role in the metabolism of fatty acids and shows important antioxidant and anti-inflammatory properties. Systemic carnitine depletion has been described in several diseases, and it...

  3. 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.

  4. Monitoring of ketogenic diet for carnitine metabolites by subcutaneous microdialysis.

    Science.gov (United States)

    Hack, Alexandra; Busch, Verena; Pascher, Bettina; Busch, Raymonde; Bieger, Iris; Gempel, Klaus; Baumeister, Friedrich A M

    2006-07-01

    The ketogenic diet (KD) provides ketones from the degradation of free fatty acids for energy metabolism. It is a therapeutic option for pharmacoresistant epilepsies. Carnitine is the carrier molecule that transports fatty acids across the mitochondrial membrane for degradation into ketones. The integrity of this transport system is a prerequisite for an adequate ketogenic response. For monitoring of tissue metabolism with KD, we used the sampling method of s.c. microdialysis (MD), which permits minimally invasive, frequent, and extensive metabolic monitoring independent of blood tests. By using this new method, we monitored changes in carnitine metabolism induced by KD, particularly in free carnitine (C0), acetylcarnitine (C2), and hydroxybutyrylcarnitine (C4OH). Correlation of microdialysate and tissue concentrations for carnitines in vitro was about 85%. Carnitine metabolism was monitored in seven children started on a KD for pharmacoresistant epilepsy after a conventional initial fasting period. Detected metabolic changes consisted of a slight decrease in s.c. C0 and a marked increase in C2/CO and C4OH/CO levels. The levels of s.c. C4OH strongly correlate with beta-hydroxybutyrate (beta-OHB) levels in plasma providing an additional parameter for the carnitine reserve of the body and reflect an optimal ketogenic energy supply. Subcutaneous MD allows close and extensive monitoring of metabolism with a KD.

  5. 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.

  6. Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid.

    Science.gov (United States)

    Cha, Youn-Soo

    2008-01-01

    Data on the functionalities of L-carnitine on obesity, diabetes, and as an ergogenic aid are summarized as follows: Obesity: Total lipid, triglyceride, and total protein increased during the 3T3-L1 cell differentiation. However, nonesterified carnitine (NEC), acid-soluble acylcarnitine (ASAC), and acid-insoluble acylcarnitine (AIAC) concentrations were lower in the differentiated 3T3-L1 cells. In addition, the exogenously added carnitine inhibited the increases in triglyceride and total lipid levels. In an animal study, L-carnitine supplementation reduced serum leptin and abdominal fat weight caused by high-fat diet in C57BL/6J mice. Diabetes: In an animal study, streptozptpcin-induced diabetic rats had markedly lower IGFBP-3 than normal rats, and IGFBP-3 was increased by L-carnitine treatment, demonstrating that L-carnitine treatment of diabetic rats modulates the IGFs/IGFBPs axis. A study of Korean diabetics indicated that there is a remarkable abnormality in lipid and carnitine metabolism in Korean diabetic patients. Ergogenic aids: We investigated the separate and combined effects of L-carnitine and antioxidant supplementation on carnitine and lipid concentrations in trained and non-trained animal and humans. Supplementation of L-carnitine and antioxidants improve lipid profiles and exercise ability in exercise-trained rats. Also, both exercise training and supplementation of carnitine and antioxidants improved lipid profiles and carnitine metabolism in humans, suggesting that carnitine and antioxidant supplementation may improve exercise performance.

  7. [Effect of L-carnitine supplemented total parenteral nutrition on postoperative lipid and nitrogen utilization].

    Science.gov (United States)

    Rössle, C; Pichard, C; Roulet, M; Chiolero, R; Schutz, Y; Temler, E; Schindler, C; Zurlo, F; Jéquier, E; Fürst, P

    1988-12-15

    During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were equally and randomly divided and received isonitrogenous (0.2 gN/kg.day) and isocaloric (35 kcal/kg.day TPN over 11 days without and with L-carnitine supplementation (12 mg/kg.day). Compared with healthy controls, the total body carnitine pool was significantly reduced in both groups prior to the operation. Without supplementation carnitine concentrations were maintained, while daily provision of carnitine resulted in an elevation of total carnitine mainly due to an increase of the free fraction. Without supplementation the cumulative urinary carnitine losses were 11.5 +/- 6.3 mmol corresponding to 15.5% +/- 8.5% of the estimated total body carnitine pool. Patients receiving carnitine revealed a positive carnitine balance in the immediate postoperative phase, 11.1% +/- 19.0% of the infused carnitine being retained. After 11 days of treatment comparable values for respiratory quotient, plasma triglycerides, free fatty acids, ketone bodies, and cumulative nitrogen balance were observed. It is concluded that in the patient population studied here carnitine supplementation during postoperative TPN did not improve fat oxidation or nitrogen balance.

  8. L-carnitine therapy in home parenteral nutrition patients with abnormal liver tests and low plasma carnitine concentrations.

    Science.gov (United States)

    Bowyer, B A; Miles, J M; Haymond, M W; Fleming, C R

    1988-02-01

    Persistent abnormalities of liver function tests occur in approximately 15% of home parenteral nutrition (HPN) patients and are associated with steatosis, steatohepatitis, and, rarely, fibrosis or cirrhosis. Approximately one-third of patients with gut failure on long-term HPN have low total and free plasma carnitine concentrations, and it has been suggested that a deficiency of L-carnitine may be responsible for the steatosis and steatohepatitis in HPN patients. To determine whether administration of L-carnitine is capable of reversing steatosis in HPN patients, 4 adult women on HPN for a mean of 53 mo (range 21-80 mo) were studied before and after 1 mo of intravenous L-carnitine supplementation (1 g/day). All patients had abnormalities in standard liver function tests and low total and free plasma carnitine values. The mean total and free plasma carnitine concentrations and the mean total hepatic carnitine concentration were reduced before supplementation and rose to normal values after treatment (27.4 +/- 2.3 to 35.5 +/- 3.1 nmol/ml, 19.4 +/- 2.8 to 25.7 +/- 2.5 nmol/ml, and 3.5 +/- 0.65 to 6.5 +/- 1.2 nmol/mg of noncollagen protein, respectively). However, there were no significant changes in mean serum aspartate aminotransferase and alkaline phosphatase levels (65 +/- 21 vs. 54 +/- 12 IU and 429 +/- 220 vs. 472 +/- 224 IU, respectively), plasma free fatty acids, plasma triglycerides, hepatic free fatty acid and triglyceride concentrations, or the grade of hepatic steatosis on light microscopy. These results suggest that carnitine deficiency is not a major cause of steatosis and steatohepatitis in patients receiving HPN.

  9. 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

  10. Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation.

    Science.gov (United States)

    Ziats, Mark N; Comeaux, Mathew S; Yang, Yaping; Scaglia, Fernando; Elsea, Sarah H; Sun, Qin; Beaudet, Arthur L; Schaaf, Christian P

    2015-09-01

    Disorders of carnitine biosynthesis have recently been associated with neurodevelopmental syndromes such as autism spectrum disorder (ASD). A 4-year-old male with autism and two episodes of neurodevelopmental regression was identified to have a mutation in the TMLHE gene, which encodes the first enzyme in the carnitine biosynthesis pathway, and concurrent carnitine deficiency. Following carnitine supplementation, the patient's regression ended, and the boy started gaining developmental milestones. This case report suggests that deficits in carnitine biosynthesis may be responsible for some cases of regression in individuals with ASD, and that testing for the respective biochemical pathway should be considered. Furthermore, this case suggests that carnitine supplementation may be useful in treating (and potentially preventing) regressive episodes in patients with carnitine deficiency. Further work to better define the role of disorders of carnitine biosynthesis in autism spectrum disorder is warranted.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    and muscle tissue with and without L-carnitine supplementation to evaluate the current treatment strategy of not recommending L-carnitine supplementation to Faroese 3-MCCd patients. Methods: Blood and urine samples and muscle biopsies were collected from patients at inclusion and at 3 months. Eight patients...... received L-carnitine supplementation when recruited; five did not. Included patients who received supplementation were asked to stop L-carnitine, the others were asked to initiate L-carnitine supplementation during the study. Symptoms were determined by review of hospital medical records and questionnaires...... carnitine levels, 6.9 (SD 1.4) μmol/L and 785 (SD 301) nmol/g wet weight, respectively. L-Carnitine supplementation increased muscle and plasma carnitine levels to a low-normal range, 25.5 (SD 10.9) μmol/L and 1,827 (SD 523) nmol/g wet weight, p

  12. 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...

  13. Carnitine Deficiency as the Possible Etiology of Idiopathic Mitral Valve Prolapse

    OpenAIRE

    Trivellato, Mario; De Palo, Elio; Gatti, Rosalba; Parenti, Anna; Piazza, Mario

    1984-01-01

    Idiopathic mitral valve prolapse (IMVP) is a very common cardiac abnormality that may be linked to carnitine deficit (inadequate nutritional intake or absorption). One patient with IMVP and related symptoms that were resistant to drug therapy was fully studied. Free plasma carnitine and 24-hour free urine carnitine were measured twice, 10 days apart, after an overnight fast.

  14. 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

  15. Low plasma carnitine in patients on prolonged total parenteral nutrition: association with low plasma lysine.

    Science.gov (United States)

    Berner, Y N; Larchian, W A; Lowry, S F; Nicroa, R R; Brennan, M F; Shike, M

    1990-01-01

    Plasma carnitine levels were determined in 17 patients maintained on long-term total parenteral nutrition (TPN) for a mean (+/- SEM) period of 69 +/- 11 months (range 12-196). All had severe malabsorption and were dependent on intravenous feeding. Plasma carnitine was determined by a modified Cederblad enzymatic method. Mean plasma carnitine was significantly below the mean normal for females (p less than 0.02) and borderline low for males (p = 0.07). In six patients the levels were below the low normal range, and in five others they were at the lowest levels of normal. Of the six patients with normal levels, three had elevated serum creatinine, indicating renal dysfunction which may by itself elevate plasma carnitine. In 10 patients the plasma levels of lysine (a carnitine precursor) were determined and found to be lower than normal (p less than 0.05). Plasma carnitine levels correlated positively with serum albumin (r = 0.62, p less than 0.05), and negatively with serum alkaline phosphatase (r = -0.64, p less than 0.05). Thus, patients maintained on long-term TPN may have low plasma carnitine, which could represent carnitine deficiency. The low plasma carnitine may be related to a deficiency of the carnitine precursor lysine. Further studies are required to determine the significance of the low plasma carnitine and whether carnitine supplementation should be required in long-term TPN.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-05-01

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

  17. Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

    Science.gov (United States)

    Li, Jia-Min; Li, Ling-Yu; Qin, Xun; Ning, Li-Jun; Lu, Dong-Liang; Li, Dong-Liang; Zhang, Mei-Ling; Wang, Xin; Du, Zhen-Yu

    2017-01-01

    Excess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation. L-carnitine significantly decreased the lipid content in liver and muscle, accompanied by increased concentrations of total and free carnitine in tissues. Meanwhile, L-carnitine enhanced mitochondrial β-oxidation activities and the expression of carnitine palmitoyltransferase 1 mRNA significantly, whereas it depressed the mRNA expression of adipogenesis-related genes. In addition, L-carnitine caused higher glycogen deposition in the fasting state, and increased and decreased the mRNA expressions of gluconeogenesis-related and glycolysis-related genes, respectively. L-carnitine also increased the hepatic expression of mTOR in the feeding state. Taken together, dietary L-carnitine supplementation decreased lipid deposition by increasing mitochondrial fatty acid β-oxidation, and is likely to promote protein synthesis. However, the L-carnitine-enhanced lipid catabolism would cause a decrease in glucose utilization. Therefore, L-carnitine has comprehensive effects on nutrient metabolism in fish. PMID:28102299

  18. Effect of thyroxine treatment on carnitine levels in mice.

    Science.gov (United States)

    Cederblad, G; Engström, G

    1978-07-01

    The effect in mice of 8 subcutaneous injections of 20 microgram of L-thyroxine at 12 hr-intervals on the carnitine concentration in the heart and skeletal muscle tissue was studied. In skeletal muscle tissue, the thyroxine treatment resulted in a depressed carnitine concentration. The mean values were 1.59 +/- 0.034 (S.E.M.) and 2.03 +/- 0.045 mumol/g noncollagen protein and 1.11 +/- 0.035 and 1.45 +/- 0.037 mumol/g dry weight for the thyroxine treated and the control animals, respectively. Thyroxine produced myocardial hypertrophy. The thyroxine treated animals had lower cardiac values when dry weight was used as reference base 4.17 +/- 0.10 mumol/g dry weight than the control group, 4.69 +/- 0.18 mumol/g dry weight. No statistically significant difference was found between the two groups when the cardiac carnitine concentration was expressed per g noncollagen protein or as carnitine in the entire hearts. Thus, thyroxine has been showed to influence the metabolism of carnitine in mice.

  19. Postheparin plasma lipases and carnitine in infants during parenteral nutrition.

    Science.gov (United States)

    Rovamo, L

    1985-03-01

    Lipoprotein lipase is the rate-limiting factor for hydrolyzing triglycerides to glycerol and fatty acids. Carnitine is a cofactor in the transport of long-chain fatty acids through the mitochondrial membrane for oxidation. To assess these determinants of fat utilization during total parenteral nutrition, lipoprotein and hepatic lipase activities and carnitine concentrations of nine newborn infants, operated on because of gastrointestinal anomalies during the first day of life, were measured with specific methods. Total parenteral nutrition was built up in 3 days whereafter the infants received 3 g/kg of fat at a constant rate of infusion for 24 h/day. Lipoprotein lipase activity of post-heparin plasma increased from 14 to 35 mumol free fatty acids/ml/h during parenteral nutrition whereas hepatic lipase activity remained unchanged at 40 mumol free fatty acids/ml/h. Serum free carnitine and acylcarnitine levels decreased significantly during parenteral nutrition; urinary excretion of carnitine decreased also. In addition, serum cholesterol and phospholipids increased markedly during parenteral nutrition whereas serum triglycerides, free fatty acids, and blood beta-hydroxybutyrate remained unchanged. Serum apolipoprotein A-I concentrations were unaltered, apolipoprotein A-II underwent a transient increase, and apolipoprotein B increased monotonically during parenteral nutrition. The results suggest that under the present circumstances neither lipoprotein lipase activity nor carnitine resources are rate-limiting for the utilization of fat in newborn infants during total parenteral nutrition.

  20. 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...

  1. Enantiomeric Resolution on L-Carnitine Selective Polymers Prepared by Molecular Imprinting

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.

  2. Enantiomeric Resolution on L—Carnitine Selective Polymers Prepared by Molecular Imprinting

    Institute of Scientific and Technical Information of China (English)

    XiaoTaoLI; GuangGuangJIANG; 等

    2002-01-01

    L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine.The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule,while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.

  3. Effects of L-carnitine in patients with hepatic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Mariano Malaguarnera; Giovanni Pistone; Rampello Elvira; Carmelo Leotta; Linda Scarpello; Rampello Liborio

    2005-01-01

    AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE).METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection,21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind.RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P<0.05) afler the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P<0.05).CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.

  4. Carnitine supplementation accelerates normalization of food intake depressed during TPN.

    Science.gov (United States)

    Laviano, A; Meguid, M M; Renvyle, T; Yang, Z J; Beverly, J L

    1996-07-01

    When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3-4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3-4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls (n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group (n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.

  5. Urinary excretion of carnitine in multiply injured patients on different regimens of total parenteral nutrition.

    Science.gov (United States)

    Cederblad, G; Schildt, B; Larsson, J; Liljedahl, S O

    1983-04-01

    Carnitine derives from intake of preformed exogenous carnitine and synthesis from lysine and methionine, but is absent in parenteral fluids. Urinary excretions of carnitine and its derivatives was measured in 30 patients 2-8 days after severe multiple injuries and compared with controls. The patients received five different isocaloric parenteral nutritional regimens;group 1 glucose and fat, group 2 glucose, fat and amino acids, group 3 glucose and insulin, group 4 glucose and amino acids, and group 5 branched-chain amino acids. The mean total carnitine excretion in healthy men was 420 mumol/24 h +/- 57 (SEM), and in women 266 mumol/24 h +/- 29, 41% of which was free carnitine. Mean excretion of total carnitine during days 2-8 after trauma for the five groups was: 900 +/- 100, 1169 +/- 112, 1251 +/- 102, 1023 +/- 117, and 668 +/- 128 mumol/24 h, being significantly higher in groups 1-4 than in healthy men. The free carnitine fraction in the patients was significantly higher than in controlled healthy subjects. Total carnitine excretion was unaffected by different nutritional regimens in the very first days. During days 6-8, group 5, receiving branched-chain amino acids had lower excretion of total carnitine (compared to groups 2-4) and free carnitine (compared to groups 3-4). Groups 3 and 4 excreted a higher percentage as free carnitine compared to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Carnitine deficiency with hyperbilirubinemia, generalized skeletal muscle weakness and reactive hypoglycemia in a patient on long-term total parenteral nutrition: treatment with intravenous L-carnitine.

    Science.gov (United States)

    Worthley, L I; Fishlock, R C; Snoswell, A M

    1983-01-01

    Low levels of plasma carnitine and reduced urinary carnitine excretion with persistently elevated plasma bilirubin levels, reactive hypoglycemia and generalized skeletal muscle weakness are described in a patient requiring long-term total parenteral nutrition (TPN). Intravenous administration of L-carnitine at 400 mg/day for 7 days and subsequently a maintenance dose of 60 mg/day corrected the plasma carnitine deficiency and reactive hypoglycemia and was associated with a return to normal plasma bilirubin levels and a restoration of skeletal muscle strength.

  7. Effect of L-carnitine and acetyl-L-carnitine on the human erythrocyte membrane stability and deformability.

    Science.gov (United States)

    Arduini, A; Rossi, M; Mancinelli, G; Belfiglio, M; Scurti, R; Radatti, G; Shohet, S B

    1990-01-01

    In this study we examined the effect of carnitine and acetylcarnitine on the human erythrocyte membrane stability and membrane deformability. Since erythrocyte membranes are impermeable to these compounds, we resealed erythrocyte ghosts in the presence of different concentrations of carnitine or acetylcarnitine. Resealed ghosts can be adequately studied in their cellular deformability and membrane stability properties by means of ektacytometry. Both carnitine and acetylcarnitine alter the membrane stability but not membrane deformability of the red cell membrane. Resealed ghosts containing 20, 50, 150, and 300 microM carnitine had 1.1, 1.6, 0.9, and 0.7 times the normal stability. While resealed ghosts containing 20, 50, 150, and 300 microM acetylcarnitine had 1.1, 1.5, 1.3, and 1.2 times the normal stability. Such changes were found to be reversible. We also conducted SDS PAGE of cytoskeletal membrane proteins from membrane fragments and residual membranes produced during membrane stability analysis, and unsheared resealed membranes in those samples where we observed an increase or a decrease of membrane stability. No changes in the cytoskeletal membrane proteins were noticed, even when the samples, prior SDS PAGE analysis, were treated with or without dithiothreitol. In addition, fluorescence steady state anisotropy of DPH in the erythrocyte membrane treated with carnitine or acetylcarnitine shows no modification of the lipid order parameter. Our results would suggest that both carnitine and its acetyl-ester, at physiological concentrations, may increase membrane stability in mature erythrocytes, most likely via a specific interaction with one or more cytoskeletal proteins, and that this effect would manifest when the erythrocytes are subjected to high shear stress.

  8. Changes in the levels of l-carnitine, acetyl-l-carnitine and propionyl-l-carnitine are involved in perfluorooctanoic acid induced developmental cardiotoxicity in chicken embryo.

    Science.gov (United States)

    Jiang, Qixiao; Wang, Chunbo; Xue, Chan; Xue, Lingfang; Wang, Meiting; Li, Changhao; Deng, Ziwen; Wang, Qian

    2016-12-01

    Perfluorooctanoic acid (PFOA), a persistent organic pollutant, is associated with developmental toxicity. This study investigated the mechanism of PFOA-induced developmental cardiotoxicity in chicken embryo, focusing on the interactions between developmental exposure to PFOA and the levels of l-carnitine (LC), acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC) in the heart. To evaluate the developmental cardiotoxicity, fertile chicken eggs were exposed to 0.1, 0.5, 1, 2 or 5mg/kg PFOA via air cell injection. Furthermore, exposure to 2mg/kg PFOA, with or without 100mg/kg LC were applied to investigate the effects of LC supplement. The results of functional and morphological assessments confirmed PFOA induced developmental cardiotoxicity in chicken embryo, which could be alleviated by co-exposure to LC. LC-MS/MS results also revealed remarkable decrease in LC, ALC and PLC levels in embryonic day six (ED6) chicken embryo hearts as well as LC level in embryonic day fifteen (ED15) chicken embryo hearts following developmental exposure to 2mg/kg PFOA. Meanwhile, co-exposure to 100mg/kg LC significantly elevated the levels of LC, ALC and PLC in chicken embryo hearts. Significantly elevated expression level of carnitine acetyltransferase (CRAT) in PFOA-exposed ED6 chicken embryo hearts was observed via western blotting, while LC co-exposure counteracted such changes. In conclusion, changes in the levels of LC, ALC and PLC in early embryonic stages are associated with PFOA induced developmental cardiotoxicity in chicken embryos.

  9. Requirements for Carnitine Shuttle-Mediated Translocation of Mitochondrial Acetyl Moieties to the Yeast Cytosol

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    Harmen M. van Rossum

    2016-05-01

    Full Text Available In many eukaryotes, the carnitine shuttle plays a key role in intracellular transport of acyl moieties. Fatty acid-grown Saccharomyces cerevisiae cells employ this shuttle to translocate acetyl units into their mitochondria. Mechanistically, the carnitine shuttle should be reversible, but previous studies indicate that carnitine shuttle-mediated export of mitochondrial acetyl units to the yeast cytosol does not occur in vivo. This apparent unidirectionality was investigated by constitutively expressing genes encoding carnitine shuttle-related proteins in an engineered S. cerevisiae strain, in which cytosolic acetyl coenzyme A (acetyl-CoA synthesis could be switched off by omitting lipoic acid from growth media. Laboratory evolution of this strain yielded mutants whose growth on glucose, in the absence of lipoic acid, was l-carnitine dependent, indicating that in vivo export of mitochondrial acetyl units to the cytosol occurred via the carnitine shuttle. The mitochondrial pyruvate dehydrogenase complex was identified as the predominant source of acetyl-CoA in the evolved strains. Whole-genome sequencing revealed mutations in genes involved in mitochondrial fatty acid synthesis (MCT1, nuclear-mitochondrial communication (RTG2, and encoding a carnitine acetyltransferase (YAT2. Introduction of these mutations into the nonevolved parental strain enabled l-carnitine-dependent growth on glucose. This study indicates intramitochondrial acetyl-CoA concentration and constitutive expression of carnitine shuttle genes as key factors in enabling in vivo export of mitochondrial acetyl units via the carnitine shuttle.

  10. Peroxisomes contribute to the acylcarnitine production when the carnitine shuttle is deficient.

    Science.gov (United States)

    Violante, Sara; Ijlst, Lodewijk; Te Brinke, Heleen; Koster, Janet; Tavares de Almeida, Isabel; Wanders, Ronald J A; Ventura, Fátima V; Houten, Sander M

    2013-09-01

    Fatty acid β-oxidation may occur in both mitochondria and peroxisomes. While peroxisomes oxidize specific carboxylic acids such as very long-chain fatty acids, branched-chain fatty acids, bile acids, and fatty dicarboxylic acids, mitochondria oxidize long-, medium-, and short-chain fatty acids. Oxidation of long-chain substrates requires the carnitine shuttle for mitochondrial access but medium-chain fatty acid oxidation is generally considered carnitine-independent. Using control and carnitine palmitoyltransferase 2 (CPT2)- and carnitine/acylcarnitine translocase (CACT)-deficient human fibroblasts, we investigated the oxidation of lauric acid (C12:0). Measurement of the acylcarnitine profile in the extracellular medium revealed significantly elevated levels of extracellular C10- and C12-carnitine in CPT2- and CACT-deficient fibroblasts. The accumulation of C12-carnitine indicates that lauric acid also uses the carnitine shuttle to access mitochondria. Moreover, the accumulation of extracellular C10-carnitine in CPT2- and CACT-deficient cells suggests an extramitochondrial pathway for the oxidation of lauric acid. Indeed, in the absence of peroxisomes C10-carnitine is not produced, proving that this intermediate is a product of peroxisomal β-oxidation. In conclusion, when the carnitine shuttle is impaired lauric acid is partly oxidized in peroxisomes. This peroxisomal oxidation could be a compensatory mechanism to metabolize straight medium- and long-chain fatty acids, especially in cases of mitochondrial fatty acid β-oxidation deficiency or overload.

  11. Effect of L-carnitine on the hepatic transcript profile in piglets as animal model

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    Kluge Holger

    2011-10-01

    Full Text Available Abstract Background Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown. Methods To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver. Results Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation. Conclusion The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    I Amiri

    2008-01-01

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

  14. Multiple AMPK activators inhibit L-Carnitine uptake in C2C12 skeletal muscle myotubes.

    Science.gov (United States)

    Shaw, Andy; Jeromson, Stewart; Watterson, Kenneth R; Pediani, John D; Gallagher, Iain; Whalley, Tim; Dreczkowski, Gillian; Brooks, Naomi; Galloway, Stuart; Hamilton, D Lee

    2017-03-15

    Mutations in the gene that encodes the principal L-Carnitine transporter, OCTN2, can lead to a reduced intracellular L-Carnitine pool and the disease Primary Carnitine Deficiency. L-Carnitine supplementation is used therapeutically to increase intracellular L-Carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake we hypothesised that AMPK activating compounds and insulin would increase L-Carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level and immunohistochemistry confirmed expression at the protein level. Contrary to our hypothesis, despite significant activation of PKB and 2DG uptake, insulin did not increase L-Carnitine uptake at 100nM. However, L-Carnitine uptake was modestly increased at a dose of 150nM insulin. A range of AMPK activators that increase intracellular calcium content [caffeine (10mM, 5mM, 1mM, 0.5mM), A23187 (10μM)], inhibit mitochondrial function [Sodium Azide (75μM), Rotenone (1μM), Berberine (100μM), DNP (500μM)] or directly activate AMPK [AICAR (250μM)] were assessed for their ability to regulate L-Carnitine uptake. All compounds tested significantly inhibited L-Carnitine uptake. Inhibition by caffeine was not dantrolene (10μM) sensitive. Saturation curve analysis suggested that caffeine did not competitively inhibit L-Carnitine transport. However, the AMPK inhibitor Compound C (10μM) partially rescued the effect of caffeine suggesting that AMPK may play a role in the inhibitory effects of caffeine. However, caffeine likely inhibits L-Carnitine uptake by alternative mechanisms independently of calcium release. PKA activation or direct interference with transporter function may play a role.

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

    Directory of Open Access Journals (Sweden)

    Eman Ramadan

    2014-07-01

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

  16. Serum carnitine as an independent biomarker of malnutrition in patients with impaired oral intake

    OpenAIRE

    Iwamoto, Junichi; Honda, Akira; Miyamoto, Yasunori; Miyazaki, Teruo; Murakami, Masashi; Saito, Yoshifumi; Ikegami, Tadashi; Miyamoto, Jiro; Matsuzaki, Yasushi

    2014-01-01

    Carnitine is a vitamin-like compound that plays important roles in fatty acid β-oxidation and the control of the mitochondrial coenzyme A/acetyl-CoA ratio. However, carnitine is not added to ordinary enteral nutrition or total parenteral nutrition. In this study, we determined the serum carnitine concentrations in subjects receiving ordinary enteral nutrition (EN) or total parenteral nutrition (TPN) and in patients with inflammatory bowel diseases to compare its levels with those of other nut...

  17. Plasma free and total carnitine measured in children by tandem mass spectrometry

    OpenAIRE

    J.H. Osorio; Pourfarzam, M.

    2002-01-01

    Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is valid...

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

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    Alina Kępka

    2016-03-01

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

  19. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

    Science.gov (United States)

    Jang, Jiwoong; Park, Jonghoon; Chang, Hyukki; Lim, Kiwon

    2016-12-01

    l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg(-1)·day(-1)) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Emaus, R.; Bieber, L.L.

    1982-01-15

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

  2. 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

  3. Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

    Directory of Open Access Journals (Sweden)

    Hyun-Seok Cho

    2012-02-01

    Full Text Available Carnitine (?#11112;ydroxy-?#15220;rimethylaminobutyric acid is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramatically to oral carnitine supplementation.

  4. L-carnitine supplementation and EPO requirement in children on chronic hemodialysis.

    Science.gov (United States)

    Aoun, Bilal; Bérard, Etienne; Vitkevic, Renata; Dehée, Axelle; Bensman, Albert; Ulinski, Tim

    2010-03-01

    L-carnitine supplementation has been the subject of heated discussion in the context of the treatment of pediatric hemodialysis patients. The aim of this study was to analyze the effect of intravenous L-carnitine supplementation on the erythropoetin (EPO) requirement in six pediatric hemodialysis patients. All patients were on intravenous L-carnitine (2.5 g per session for patients >30 kg and 1 g for those carnitine supplementation, the EPO requirement was 1.15 +/- 0.22 (range 0.37-1.75) microg/kg darbepoetin alpha. Free carnitine (FC) levels were measured before (40.4 +/- 4.9 micromol/l), immediately after the 9-month L-carnitine supplementation period (378.5 +/- 77.3 micromol/l), and 4 months after withdrawal of L-carnitine (95.6 +/- 4.0 micromol/l). After 9 months, the EPO dose was 0.47 +/- 0.10 microg/kg (p carnitine supplementation, FC levels were higher and persisted longer than expected. This rise was associated with increased Hb levels and decreased EPO requirement. Since controls were missing for this study, prospective long-term multi-center studies on a large number of patients are required to provide solid answers to the controversial question of L-carnitine supplementation in hemodialyzed children.

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

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    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

  6. Carnitine depletion during total parenteral nutrition despite oral L-carnitine supplementation.

    Science.gov (United States)

    Hirose, S; Hirata, M; Azuma, N; Shirai, Z; Mitudome, A; Oda, T

    1997-04-01

    Carnitine CAR) plays an important role in the beta-oxidation of fatty acids. Less attention. however, has been paid to CAR compared to other nutrients even in total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR level was measured in a 3-year-old boy receiving long-term TPN because of short bowel syndrome. Both the total and acyl CAR in the serum were evaluated under various nutritional conditions including oral supplementation of L-CAR. Low CAR concentrations were observed especially when lipid containing TPN regimens were in place. Oral L-CAR supplementation was not sufficient to restore the low CAR levels in the present index patient even when the dose was increased to 120 mg/kg in accordance with the result of the L-CAR absorption test that revealed poor intestinal absorption of this nutrient. Moreover, a markedly low CAR level was measured during the onset of sepsis in the patient, and the blood CAR was depleted when lipid metabolism was activated by lipid loading or sepsis. To date, the late effects of CAR depletion on child growth have not been well examined. It is recommended that the blood CAR level be maintained at normal levels before any prominent manifestations of the deficiency have developed. The intravenous administration of CAR appears to be necessary to supply a sufficient amount of CAR for patients with severe malabsorption.

  7. 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

    OpenAIRE

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

    2006-01-01

    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 car...

  8. Effects of L-carnitine on growth performance, carcass composition, and metabolism of lipids in male broilers.

    Science.gov (United States)

    Xu, Z R; Wang, M Q; Mao, H X; Zhan, X A; Hu, C H

    2003-03-01

    We studied the effects of L-carnitine on growth performance, carcass composition, and lipid metabolism in male broilers. Six hundred male commercial broilers were allotted to five groups, each of which included three replicates (40 birds per replicate). The groups received the same basal diet supplemented with 0, 25, 50, 75, or 100 mg/kg L-carnitine, respectively. The feeding trial showed that L-carnitine had no significant effect on daily gain or feed conversion. Supplementation with L-carnitine (above 25 mg/kg) in the diet increased breast muscle yield (P carnitine to the diet decreased total activities of glucose-6-phosphate dehydrogenase, malic dehydrogenase, isocitrate dehydrogenase, and lipoprotein lipase (P subcutaneous fat and total activity of carnitine palmitoyltransferase-I (P carnitine could reduce the deposit of subcutaneous fat by decreasing total activities of enzymes in the fat and enhance intramuscular fat by decreasing the activity of carnitine palmitoyltransferase-I in breast muscles.

  9. L-carnitine: effect of intravenous administration on fuel homeostasis in normal subjects and home-parenteral-nutrition patients with low plasma carnitine concentrations.

    Science.gov (United States)

    Bowyer, B A; Fleming, C R; Haymond, M W; Miles, J M

    1989-04-01

    We studied the effects of intravenous L-carnitine on the metabolism of fatty acids, ketone bodies, glucose, and branched-chain amino acids in four normal volunteers and four patients on long-term home parenteral nutrition (HPN) with low plasma carnitine concentrations. Substrate kinetics were determined by use of [1-14C]palmitate, [3,4-13C2]-acetoacetate, [6,6-2H2]glucose, and [5,5,5-2H3]leucine before and during a 3-h intravenous infusion of L-carnitine. HPN patients were restudied after 1 mo of nightly intravenous carnitine administration. HPN patients tolerated the short-term fast well, exhibiting neither hypoglycemia nor hypoketonemia. Intravenous carnitine had no effect on rates of fatty acid oxidation, ketone body production, glucose production, or leucine kinetics in either group. Routine addition of carnitine to the HPN regimen does not appear to be necessary. The failure of L-carnitine administration to have discernable effects on intermediary metabolism in normal volunteers casts doubt on its role in the treatment of a variety of medical conditions.

  10. Oral carnitine supplementation for dyslipidemia in chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Afsoon Emami Naini

    2012-01-01

    Full Text Available Carnitine deficiency is a commonly observed problem in maintenance hemodialysis (MHD patients, which results in altered metabolism of fatty acids and subsequently development of dyslipidemia. To evaluate the effect of oral L-carnitine (LC supplementation on lipid profile of adult MHD patients, we studied 30 of them (19 males, 11 females who received LC supplementation of 250 mg tablets three times a day for eight weeks. They were compared with 30 matched patients as a control group. Serum lipid profiles were compared before and after the intervention between the two groups. There was a significant decrease of the values of the lipid profile in the intervention group before and after carnitine supplementation including the mean values of total cholesterol (190 ± 36.8 vs. 177 ± 31.2 mg/dL, triglyceride (210 ± 64.7 vs. 190 ± 54.1 mg/dL and LDL-cholesterol (117 ± 30.1 vs. 106 ± 26.3 mg/dL, while the values did not change siginificantly from base line in the control group. However, the difference for HDL-cholesterol in intervention group was not statistically significant. None of the patients dropped out of the study due to drug side effects. Oral LC supplementation (750 mg/day is able to improve lipid profile in patients on MHD. Further long-term studies with adequate sample size are needed to define the population of patients who would benefit more from carnitine therapy and the optimal dose and the most efficient route for administration of the drug.

  11. Oral carnitine supplementation for dyslipidemia in chronic hemodialysis patients.

    Science.gov (United States)

    Naini, Afsoon Emami; Sadeghi, Masoumeh; Mortazavi, Mojgan; Moghadasi, Mojdeh; Harandi, Asghar Amini

    2012-05-01

    Carnitine deficiency is a commonly observed problem in maintenance hemodialysis (MHD) patients, which results in altered metabolism of fatty acids and subsequently development of dyslipidemia. To evaluate the effect of oral L-carnitine (LC) supplementation on lipid profile of adult MHD patients, we studied 30 of them (19 males, 11 females) who received LC supplementation of 250 mg tablets three times a day for eight weeks. They were compared with 30 matched patients as a control group. Serum lipid profiles were compared before and after the intervention between the two groups. There was a significant decrease of the values of the lipid profile in the intervention group before and after carnitine supplementation including the mean values of total cholesterol (190 ± 36.8 vs. 177 ± 31.2 mg/dL), triglyceride (210 ± 64.7 vs. 190 ± 54.1 mg/dL) and LDL-cholesterol (117 ± 30.1 vs. 106 ± 26.3 mg/dL), while the values did not change siginificantly from base line in the control group. However, the difference for HDL-cholesterol in intervention group was not statistically significant. None of the patients dropped out of the study due to drug side effects. Oral LC supplementation (750 mg/day) is able to improve lipid profile in patients on MHD. Further long-term studies with adequate sample size are needed to define the population of patients who would benefit more from carnitine therapy and the optimal dose and the most efficient route for administration of the drug.

  12. L-carnitine Reduces Muscle Cramps in Patients With Cirrhosis.

    Science.gov (United States)

    Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Nakakuki, Natsuko; Takada, Hitomi; Matsuda, Shuya; Gondo, Kouichi; Asano, Yu; Hattori, Nobuhiro; Tamaki, Nobuharu; Suzuki, Shoko; Yasui, Yutaka; Hosokawa, Takanori; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2015-08-01

    We performed a prospective study to evaluate the ability of L-carnitine, which is involved in the β-oxidation of fatty acids, to reduce muscle cramps in patients with cirrhosis. Consecutive patients with cirrhosis and muscle cramps were given L-carnitine 300 mg, 3 times/day (900 mg/day, n = 19) or 4 times/day (1200 mg/day, n = 23) for 8 weeks. The frequency of muscle cramps was assessed by questionnaires, and the degree of muscle cramping was assessed by using the visual analogue scale (VAS). Muscle cramping was reduced in 88.1% of all subjects at the end of the 8-week study period and disappeared for 28.6% of patients. Overall VAS scores decreased significantly from 69.9 ± 22.5 at baseline to 26.2 ± 29.1 after 8 weeks (P muscle cramps after 8 weeks (43.5% in the 1200 mg/day group vs 10.5% in the 900 mg/day group, P = .037) and VAS scores at 8 weeks (9.9 ± 13.5 in the 1200 mg/day group vs 39.6 ± 31.9 in the 900 mg/day group, P = .003). No adverse events were reported. Therefore, L-carnitine appears to be safe and effective for reducing liver cramps in patients with cirrhosis.

  13. 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.

  14. 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)....

  15. Enhanced lipid utilization in infants receiving oral L-carnitine during long-term parenteral nutrition.

    Science.gov (United States)

    Helms, R A; Whitington, P F; Mauer, E C; Catarau, E M; Christensen, M L; Borum, P R

    1986-12-01

    Fourteen infants requiring long-term total parenteral nutrition but able to tolerate small quantities of enteral feedings were randomized into carnitine treatment and placebo control groups. All infants had received nutritional support devoid of carnitine. Plasma carnitine levels and observed plasma lipid indices were not different before supplementation. Under standardized, steady-state conditions, 0.5 g/kg fat emulsion (intralipid) was administered intravenously over 2 hours both before and after infants received 7 days of continuous nasogastric or gastric tube L-carnitine (50 mumol/kg/day) or placebo. Plasma triglyceride, free fatty acid, acetoacetate, beta-hydroxybutyrate, and carnitine concentrations were observed at 0 (start of lipid infusion), 2, and 4 hours for pre- and post-treatment periods, and in addition at 6 and 8 hours after carnitine supplementation. Infants receiving carnitine had significantly greater beta-hydroxybutyrate plasma concentrations (P less than 0.05) and carnitine (P less than 0.001) at 0, 2, 4, 6, and 8 hours, and greater plasma acetoacetate concentrations (P less than 0.05) at 2, 4, 6, and 8 hours, compared with controls. Twenty-four-hour urinary carnitine excretion was very low for both groups before supplementation; after supplementation, excretion was higher (P less than 0.05) in the carnitine group. No significant differences were found between groups for plasma triglyceride or free fatty acid concentrations at any observation period. This study demonstrated enhanced fatty acid oxidation, as evidenced by increased ketogenesis, with L-carnitine supplementation in infants receiving long-term total parenteral nutrition.

  16. Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates.

    Science.gov (United States)

    Bonner, C M; DeBrie, K L; Hug, G; Landrigan, E; Taylor, B J

    1995-02-01

    The effects of parenteral L-carnitine supplementation on fat metabolism, nutrient intake, and plasma and erythrocyte carnitine concentrations were studied in 43 very low birth weight infants. Infants were randomly assigned to control or carnitine-supplemented (50 mumol/kg per day) groups within two weight categories: group 1, 750 to 1000 gm, and group 2, 1001 to 1500 gm. Plasma total, free, and acyl carnitine levels, erythrocyte carnitine levels, serum beta-hydroxybutyrate and triglyceride levels, and total fat intake were monitored weekly until 50% of total caloric intake was met enterally. Neonates receiving carnitine had higher plasma carnitine levels than control groups (total carnitine: group 1, 75.2 +/- 22.9 vs 9.6 +/- 2.7 mmol/ml; group 2, 61.6 +/- 31.2 vs 13.0 +/- 9.2 nmol/ml). Levels of beta-OH-butyrate decreased from baseline in control neonates (group 1, 0.12 +/- 0.06 to 0.03 +/- 0.02 mmol/L; group 2, 0.11 +/- 0.03 to 0.05 +/- 0.02 mmol/L); they remained unchanged in supplemented groups. Thus ketogenesis appeared less impaired in infants receiving supplements. Supplemented group 2 tolerated more fat than control group 2; triglyceride levels remained acceptable in all groups. Carnitine group 2 had greater weight gain than control group 2 during the first 2 weeks of life. We conclude that very low birth weight infants requiring prolonged parenteral nutrition have carnitine deficiency with impaired ketogenesis. Parenteral administration of carnitine appears to alleviate this metabolic disturbance.

  17. Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition.

    Science.gov (United States)

    Dahlström, K A; Ament, M E; Moukarzel, A; Vinton, N E; Cederblad, G

    1990-10-01

    Total and free carnitine and acylcarnitine concentrations were analyzed in whole blood and plasma in 12 children with a mean age of 68.4 +/- 42.9 months who had received carnitine-free total parenteral nutrition (TPN) for an average of 4 years. The purpose of the study was to see if the children had become carnitine deficient and, if so, whether this correlated with poor lipid clearance. Compared to controls, the TPN-dependent children had significantly decreased concentrations of total and free carnitine in blood (26.6 +/- 9.4 (SD) mumols/L vs. 43.3 +/- 9.1 mumols/L, p less than 0.001, and 17.1 +/- 7.7 mumols/L vs. 35.2 +/- 8.1 mumols/L, p less than 0.001, respectively). Similar results were found in plasma (total carnitine of 19.0 +/- 8.0 mumols/L vs. 41.9 +/- 5.2 mumols/L, p less than 0.001, and free carnitine of 15.7 +/- 7.3 mumols/L vs. 36.1 +/- 5.2 mumols/L, p less than 0.001, respectively). The acylcarnitine concentration in plasma was decreased in the TPN children (3.3 +/- 1.5 mumols/L vs. 5.8 +/- 3.0 mumols/L, p less than 0.01) compared to controls. Despite the low carnitine concentrations, serum triglyceride levels and serum free fatty acid levels were within the normal range. There was no correlation between carnitine concentrations in plasma and serum triglyceride and free fatty acid levels. Our data show that children receiving carnitine-free TPN for many years developed markedly decreased concentrations of carnitine in blood and plasma. However, no adverse effects of the low carnitine levels were found on triglyceride and free fatty acid metabolism under stable conditions.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    V. V. Mikhaylichenko

    2014-01-01

    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.

  20. Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart.

    Science.gov (United States)

    Gómez, Luis A; Heath, Shi-Hua D; Hagen, Tory M

    2012-01-01

    The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (pcarnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics.

  1. The study of serum Carnitine, Triglyceride and Cholesterol changes in pregnant and non-pregnant women

    Directory of Open Access Journals (Sweden)

    Zahraei M

    1993-04-01

    Full Text Available Carnitine is a water-soluble quaternary amine which increases the long-chain fatty acid metabolism by facilitation of their transport to the oxidation site (mitochondria. Carnitine most likely is present in all animal species, in many microorganisms, and in many plants. In this study, we determined the carnitine level of sera in pregnant and non-pregnant women by segade modified method. Average concentration of carnitine in the sera of fifty pregnant women was about 25/83 umol/I: First trimester-30.96 umol/I. Second trimester-29.11 umol/I. Third trimester-25.11 umol/I. concentration of cholesterol and triglyceride in the above-mentioned group was the following: Cholesterol: 258.84 mg/dl triglyceride: 267.02 mg/dl. The above values show that the carnitine level in sera of pregnant women decreases significantly and this decrease is tolerated well by pregnant women. According to our results, the serum carnitine concentration in pregnant women gradually decreases as gestation proceeds. So that the end of this period, is half of its concentration before conception. During pregnancy, there was an inverse correlation between carnitine level and that of cholesterol and triglycerides. Decrease in carnitine concentration and increase in cholesterol and triglyceride levels may be due to the following factors: 1 Increase in FFA oxidation in pregnancy. 2 Hormones. 3 Dilution of the blood. 4 Decrease in Fe storage in pregnant women.

  2. Plasma L-carnitine levels of obese and non-obese polycystic ovary syndrome patients.

    Science.gov (United States)

    Celik, Fatih; Kose, Mesut; Yilmazer, Mehmet; Köken, Gülengül N; Arioz, Dagistan Tolga; Kanat Pektas, Mine

    2017-01-31

    It is well-known that plasma L-carnitine concentrations are significantly decreased in obese individuals. A study showed that L-carnitine concentrations are significantly lower in lean PCOS patients than in lean healthy women. Thus, it has been suggested that lowered L-carnitine is associated with PCOS. This study also showed that the women with PCOS had significantly lower L-carnitine levels than those of the healthy controls. In addition, this study hypothesised that low L-carnitine levels in PCOS patients were associated with obesity and/or insulin resistance. Moreover, plasma L-carnitine concentrations were found to be statistically similar in PCOS patients and healthy controls, when controlled for obesity. This study implied that L-carnitine could be used as an adjunctive therapy in the management of insulin resistance or obesity in women who have PCOS. Further research might be planned to clarify the clinical effects of L-carnitine administration in PCOS patients with insulin resistance and/or obesity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.J.

    1989-01-01

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

  4. 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…

  5. 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

  6. Effect of L-carnitine Supplementation on Nutritional Status and Physical Performance Under Calorie Restriction.

    Science.gov (United States)

    Jain, Swati; Singh, Som Nath

    2015-04-01

    L-carnitine is popular as a potential ergogenic aid because of its role in the conversion of fat into energy. The present study was undertaken to investigate the effect of short term supplementation of L-carnitine on metabolic markers and physical efficiency tests under short term calorie restriction. Male albino rats were divided into four groups (n = 12 in each)-control, calorie restricted (CR for 5 days, 25 % of basal food intake), L-carnitine supplemented (CAR, given orally for 5 days at a dose of 100 mg/kg), CR with L-carnitine supplementation (CR + CAR). Food intake and body weight of the rats were measured along with biochemical variables like blood glucose, tissue glycogen, plasma and muscle protein and enzymatic activities of CPT-1 (carnitine palmitoyl transferase-1) and AMP kinase. Results demonstrated that L-carnitine caused marked increase in muscle glycogen, plasma protein, CPT-1 activity and swim time of rats (P swim time of rats than control, CR and L-carnitine treated rats (P < 0.05). The present study was an attempt towards developing an approach for better adherence to dietary restriction regimen, with the use of L-carnitine.

  7. Carnitine levels in skeletal muscle of malnourished patients before and after total parenteral nutrition.

    Science.gov (United States)

    Sandstedt, S; Larsson, J; Cederblad, G

    1986-11-01

    Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Carnitine is derived from the diet and from endogenous synthesis from lysine and methionine. About 98% of the body's carnitine pool is located in skeletal muscle tissue. Skeletal muscle carnitine levels were determined in two groups of malnourished patients, eight patients with anorexia nervosa with a weight loss of 32.4% +/- 1.8 (mean +/- SEM) and six surgical patients with major gastrointestinal disorders and a weight loss of 15.2% +/- 2.7. Their hepatic and kidney functions were normal. On admission, the muscle carnitine levels were 16.9 +/- 4.0 mumol/g dry weight (mean +/- SD) for the surgical patients and 20.8 +/- 5.0 mumol/g dry weight for the anorexia nervosa patients, which corresponded to carnitine levels seen in healthy subjects. No statistical significance was found between the two groups. Total parenteral nutrition was given to the surgical patients for 2 weeks and to the anorexia nervosa patients for 3-5 weeks. No statistical difference in muscle carnitine levels was found in either group after nutritional support. These malnourished patients had no decreased muscle carnitine levels on admission and maintained them during several weeks of total parenteral nutrition.

  8. Carnitine concentrations in term and preterm newborns at birth and during the first days of life.

    Science.gov (United States)

    Honzík, T; Chrastina, R; Hansíková, H; Böhm, M; Martincová, O; Plavka, R; Zapadlo, M; Zeman, J

    2005-01-01

    Carnitine plays an important role in energetic metabolism. The aim of the study was to characterize the carnitine status in term and preterm newborns with respect to gestational age, birth weight, haematocrit and red blood cell count (RBC). The effect of nutrition on carnitine levels in the first week of life was also studied. Total blood pool of free carnitine (FC), acylcarnitines (AC) and total carnitine (TC) were analysed in whole cord blood and postnatally in capillary blood obtained at the day 4-6 in 33 term newborns and at the day 7-10 in 27 preterm newborns using tandem mass spectrometry. Plasma level of carnitine in the cord blood was measured using radioenzymatic method. Cord plasma levels of FC, AC and TC were higher in preterm newborns in comparison with term newborns (p parenteral nutrition. Our results indicate that preterm newborns are born with limited carnitine store. Interpretation of carnitine analyses in whole blood relies in addition to gestational age and birth weight on the haematocrit, especially in newborns with anaemia or blood hyperviscosity.

  9. 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.

  10. L-Carnitine Improves the Asthma Control in Children with Moderate Persistent Asthma

    Directory of Open Access Journals (Sweden)

    Mohammed Al-Biltagi

    2012-01-01

    Full Text Available The objective. was to investigate L-Carnitine level and the effects of its supplementation in children with moderate persistent Asthma. Methods. Free and total serum carnitine levels were measured in 50 children having moderate persistent asthma and 50 healthy control children. The patients group was randomly divided into two subgroups. Subgroup A was supplemented with L-carnitine for 6 months while subgroup B was used as a placebo controls. Both subgroups were assessed by pulmonary function tests (PFT and childhood-asthma control test (C-ACT before and 6 months after carnitine supplementation. Results. Total and free carnitine levels were significantly lower in patient group than in control group. PFT and C-ACT showed significant improvements in asthmatic children supplemented with L-carnitine than in those who were not supplemented. Conclusion. L-carnitine levels were initially lower in moderate persistent asthmatic children as compared to healthy control children. Asthmatic children who received L-carnitine supplementation showed statistically significant improvement of C-ACT and PFT.

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

    Science.gov (United States)

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

    2013-01-01

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

  12. 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

  13. 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

  14. The results of nationwide survey efficiency of the complex acetyl-L-carnitine and L-carnitine fumarate in the treatment of infertile marriages due to the presence of male factor

    Directory of Open Access Journals (Sweden)

    I. V. Vinogradov

    2014-12-01

    Full Text Available The article studies the influence of a complex of acetyl-L-carnitine and L-carnitine fumarate in combination therapy qualitative and quantitative indicators of sperm in men with various forms pathospermia. The study has shown that such improved performance as morphology, motility and concentration. It turned out that the treatment of complex drugs carnitine series allows you to have a spouse patients natural pregnancyin 29.57 % of cases, which does not exclude the use of drugs containing acetyl-L-carnitine and L-carnitine fumarate in preparing men to assisted reproductive technologies programs.

  15. Enhanced specific antibody response to bovine serum albumin in pigeons due to L-carnitine supplementation.

    Science.gov (United States)

    Janssens, G P; Mast, J; Goddeeris, B M; Cox, E; Hesta, M; De Wilde, R O

    2000-09-01

    1. Thirty adult female pigeons (Columba livia domestica) were randomly divided into 3 equal groups; the 1st and 2nd groups were immunised with bovine serum albumin (BSA) at 0 and 20 d, the 2nd group also received 1 g L-carnitine per litre of drinking water from -5 to 25 d post-immunisation (dpi) and the 3rd group, a control group, received neither treatment. 2. Body weights and serum samples were taken at 0, 5, 10, 15, 20, 25, 30 and 35 dpi. 3. Both BSA-specific IgG and IgM responses were enhanced by about 10% by L-carnitine supplementation. 4. L-carnitine supplemented pigeons showed a higher water consumption. Body weight loss during the onset of the immune response showed a slight tendency to be counteracted by L-carnitine supplementation. 5. The impact of L-carnitine on resistance and resilience to an immunological challenge is discussed.

  16. Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy.

    Science.gov (United States)

    Hayashi, Hisako; Tokuriki, Shuko; Okuno, Takashi; Shigematsu, Yosuke; Yasushi, Akiba; Matsuyama, Go; Sawada, Ken; Ohshima, Yusei

    2014-04-01

    Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3-hydroxyisovaleric acid (3-HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3-HIA and lowered serum C0 compared with post-menstrual age-matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and L-carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas.

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

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    Manganaro M.

    2003-06-01

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

  18. Effect of carnitine on lipid metabolism in the newborn. I. Carnitine supplementation during total parenteral nutrition in the first 48 hours of life.

    Science.gov (United States)

    Orzali, A; Donzelli, F; Enzi, G; Rubaltelli, F F

    1983-01-01

    The effect of carnitine administration on neonatal lipid metabolism was studied during endovenous loading with Intralipid (1 g/kg body weight over a 4-hour period). During a 6-hour period the plasma level of triglycerides, glycerol, free fatty acids (FFA), beta-hydroxybutyrate (beta-OHB), and acetoacetate were monitored in a group of newborns infused with carnitine and compared with a control group infused only with Intralipid. Carnitine administration caused an increased plasma concentration of ketone bodies, probably consequent to an increased rate of FFA mitochondrial beta-oxidation. An increased plasma level of glycerol and FFA was also observed, whereas the triglyceride plasma levels were not different between the two groups. Carnitine administration in the neonatal period seems to act by increasing ketogenesis and lipolysis.

  19. Influence of intravenous L-carnitine administration in sheep preceding an oral urea drench.

    Science.gov (United States)

    Chapa, A M; Fernandez, J M; White, T W; Bunting, L D; Gentry, L R; Ward, T L; Blum, S A

    1998-11-01

    Two experiments were conducted to investigate the effect of i.v. administration of L-carnitine on selected metabolites in sheep and to determine the feasibility of using L-carnitine to ameliorate the deleterious effects of hyperammonemia in sheep. In Exp. 1, i.v. L-carnitine solutions were administered at three levels in a replicated Latin square: 0 (CONT), 6.36 (CAR 1), and 12.72 (CAR 2) mmol L-carnitine/kg x (75) BW using Suffolk ewes (n = 6; average BW 75+/-3 kg). Plasma L-carnitine concentration was increased (P<.05) by treatment (51.9 vs 102.3, and 96.4 micromol/L in CONT, CAR 1, and CAR 2, respectively). Plasma glucose concentration was elevated (P<.05) in CAR 2 and CAR 1. Plasma NEFA concentration was highest (P<.05) in CAR 2. Area under the response curve for glucose was greater (P<.02) in CAR 2. In Exp. 2, Suffolk ewes (n = 16; average BW 48+/-2 kg) were used in a randomized complete block design with a 2x2 factorial treatment arrangement to determine the effects of i.v. L-carnitine administration during an oral urea load test (OULT). L-Carnitine (0 and 6.36 mmol/kg x (75) BW) was administered i.v. at 30 min, and an oral urea drench (50% wt/vol; 0 and 300 mg/kg BW) was administered at 60 min. Plasma L-carnitine was increased (P<.0001) by i.v. L-carnitine. Plasma ammonia N was highest (P<.0001) in the UREA treatment compared with the CONT, CARN, and CARN + UREA treatments (148 vs 95, 101, and 108 micromol/L, respectively). Intravenous L-carnitine administration influenced plasma glucose and NEFA concentrations in sheep and, when administered 30 min preceding an OULT, prevented the development of subclinical hyperammonemia in sheep.

  20. Carnitine deprivation adversely affects cardiac performance in the lipopolysaccharide- and hypoxia/reoxygenation-stressed piglet heart.

    Science.gov (United States)

    Penn, D; Zhang, L; Bobrowski, P J; Quinn, M; McDonough, K H

    1999-02-01

    Sepsis and hypoxia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine and develop low carnitine plasma and tissue levels. Because of its high metabolic rate and dependence on fatty acids for energy, the newborn heart may be particularly vulnerable to stress in the face of an inadequate carnitine supply. To investigate whether carnitine deprivation affects cardiac performance under stress, 23 neonatal piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN -) or supplemented (CARN +) with L-carnitine (400 mg/L). Bacterial endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or saline vehicle was administered to anesthetized piglets 3 h prior to study of isolated perfused hearts. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure, and left ventricular developed pressure (LVDP) were measured in vitro under aerobic, hypoxic, and reoxygenation conditions in all animals. Plasma and tissue carnitine values were lower in CARN - than in CARN + piglets. In hearts from LPS-treated animals prior to hypoxia, there was no difference in ventricular compliance between CARN - and CARN + groups. LVSP and LVDP were lower in CARN - than CARN + hearts. During hypoxia, LVSP and LVDP fell, but left ventricular end diastolic pressure increased in hearts from both LPS- and saline- treated piglets. Reoxygenation led to poorer recovery in CARN - than CARN + hearts from LPS-treated animals, but not from saline controls. During hypoxia/reoxygenation, lactate efflux initially rose and then fell, while carnitine efflux increased continually. Acetyl- and medium-chain acylcarnitines were detected in the coronary effluent. Our findings suggest that carnitine deprivation diminishes heart carnitine concentrations and impairs cardiac recovery from combined endotoxic and hypoxic stress. Possible mechanisms include reduced acyl buffering and

  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. Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

    Science.gov (United States)

    Pichard, C; Roulet, M; Schutz, Y; Rössle, C; Chiolero, R; Temler, E; Schindler, C; Zurlo, F; Fürst, P; Jéquier, E

    1989-02-01

    Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

  3. 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

  4. Fenofibrate Therapy in Carnitine Palmitoyl Transferase Type 2 Deficiency

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    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.

  5. 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.

  6. Critical update for the clinical use of L-carnitine analogs in cardiometabolic disorders

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    Herrera MD

    2011-03-01

    Full Text Available Carmen Mingorance, Rosalía Rodríguez-Rodríguez, María Luisa Justo, María Álvarez de Sotomayor, María Dolores HerreraDepartment of Pharmacology, School of Pharmacy, University of Seville, Seville, SpainAbstract: Acetyl-L-carnitine (ALC and propionyl-L-carnitine (PLC are two naturally occurring carnitine derivates formed by carnitine acetyltransferase. The beneficial cardiovascular effects of ALC and PLC have been extensively evaluated in animals and humans during the last 20 years. For instance, many clinical trials have suggested ALC and PLC as potential strategies in the management of peripheral arterial disease, heart and cerebral ischemia, and congestive heart failure. As a result, several experts have already aimed to revise the clinical evidence supporting the therapeutic use of ALC and PLC. On the basis of their conclusions, our aim was a critical review of the effectiveness of ALC and PLC in the treatment of cardiovascular diseases. Type 2 diabetes mellitus is an independent risk factor for the development of cardiovascular disease. Therefore we also describe recent studies that have addressed the emerging use of ALC and PLC amelioration of the insulin resistant state and its related morbidities.Keywords: propionyl-L-carnitine, acetyl-L-carnitine, L-carnitine, cardiovascular diseases, insulin resistance 

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

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    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.

  8. Ketogenic effects of low and high levels of carnitine during total parenteral nutrition in the rat.

    Science.gov (United States)

    Böhles, H J; Akcetin, Z

    1987-07-01

    Male Wistar rats received total parenteral alimentation for 3 d. The animals were divided into three groups: group 1, without L-carnitine; group 2, 10 mg (62.1 mumol) L-carnitine X kg-1 X d-1; and group 3, 100 mg (621.1 mumol) L-carnitine X kg-1 X d-1. Fat oxidation was followed by indirect calorimetry. Maximal oxidative metabolism of fatty acids was achieved with supplementation of L-carnitine in small amounts (10 mg X kg-1 X d-1). This was demonstrated by a decrease of the RQ and of the serum concentrations of fatty acids and by an increase of beta-OH-butyric acid. Decreased liver free and long-chain acylcarnitine and increased short-chain acylcarnitine concentrations in this group also demonstrate an increased ketogenicity. This ketogenic effect of carnitine decreases when higher concentrations of carnitine are used. This study demonstrates that the ketogenic effect of carnitine is dose dependent.

  9. Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington's disease patients.

    Science.gov (United States)

    Cuturic, Miroslav; Abramson, Ruth K; Moran, Robert R; Hardin, James W; Frank, Elaine M; Sellers, Andrea A

    2013-01-01

    Along with antioxidant properties, carnitine is an important regulator of lipid metabolism in humans. While beneficial effects of carnitine have been demonstrated in animal models of Huntington's disease (HD), metabolism of carnitine has not been studied in humans with this illness. In this retrospective database review from 23 patients admitted to a HD-specialized nursing home unit, we found a relatively high prevalence of hypocarnitinemia (6 cases, 26%). Our review suggests that catabolism and chronic valproate use predisposed our patients to develop hypocarnitinemia. The patients with low serum carnitine levels who received levocarnitine supplementation, during a mean period of 7.3 months, showed improvement in motor, cognitive and behavioral measures. We hypothesize that observed improvement related to the resolution of reversible metabolic encephalopathy and myopathy associated with secondary carnitine deficiency. In conclusion, notwithstanding its limitations, this is the first study to report measurements of carnitine levels in HD patients, revealing relatively high prevalence of hypocarnitinemia in our population. Our findings suggest that HD patients with hypocarnitinemia may benefit from low-dose levocarnitine supplementation. Further studies of carnitine metabolism and supplementation in HD patients are warranted.

  10. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders.

    Science.gov (United States)

    Ribas, Graziela S; Vargas, Carmen R; Wajner, Moacir

    2014-01-10

    In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood-brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential.

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

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    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

  12. 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.

  13. 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.

  14. Serum carnitine as an independent biomarker of malnutrition in patients with impaired oral intake.

    Science.gov (United States)

    Iwamoto, Junichi; Honda, Akira; Miyamoto, Yasunori; Miyazaki, Teruo; Murakami, Masashi; Saito, Yoshifumi; Ikegami, Tadashi; Miyamoto, Jiro; Matsuzaki, Yasushi

    2014-11-01

    Carnitine is a vitamin-like compound that plays important roles in fatty acid β-oxidation and the control of the mitochondrial coenzyme A/acetyl-CoA ratio. However, carnitine is not added to ordinary enteral nutrition or total parenteral nutrition. In this study, we determined the serum carnitine concentrations in subjects receiving ordinary enteral nutrition (EN) or total parenteral nutrition (TPN) and in patients with inflammatory bowel diseases to compare its levels with those of other nutritional markers. Serum samples obtained from 11 EN and 11 TPN patients and 82 healthy controls were examined. In addition, 10 Crohn's disease and 10 ulcerative colitis patients with malnutrition who were barely able to ingest an ordinary diet were also evaluated. Carnitine and its derivatives were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The carnitine concentrations in EN and TPN subjects were significantly lower compared with those of the control subjects. Neither the serum albumin nor the total cholesterol level was correlated with the carnitine concentration, although a significant positive correlation was found between the serum albumin and total cholesterol levels. Indeed, patients with CD and UC showed significantly reduced serum albumin and/or total cholesterol levels, but their carnitine concentrations remained normal. In conclusion, only a complete blockade of an ordinary diet, such as EN or TPN, caused a reduction in the serum carnitine concentration. Serum carnitine may be an independent biomarker of malnutrition, and its supplementation is needed in EN and TPN subjects even if their serum albumin and total cholesterol levels are normal.

  15. Protective role of L-carnitine supplementation against exhaustive exercise induced oxidative stress in rats.

    Science.gov (United States)

    Síktar, Elif; Ekinci, Deniz; Síktar, Erdinç; Beydemir, Sükrü; Gülçin, Ilhami; Günay, Mehmet

    2011-10-15

    The objective of this study was to investigate temperature dependent effects of oral l-carnitine supplementation on exhaustive exercise induced oxidative damage in rats. 42 male Spraque Dawley rats were randomly divided into seven experimental groups. These groups were formed as three non-carnitine exercise groups, three carnitine-exercise groups and a sedentary group. l-carnitine was given intraperitoneally to the carnitine-exercise groups 1h before the exercise in 100mg/kg. Blood was collected to measure paraoxonase-1 (PON1) activity, plasma malondialdehyde (MDA), low-density lipoprotein (LDL) and cholesterol concentrations. These biomarkers were measured in venous blood samples collected before and after the rats swam in pools at different water temperatures (18°C, 28°C and 38°C). In the non-carnitine group, exercise caused a significant decrease in PON1 activity and a significant elevation in MDA concentration at 28°C compared to the sedentary group. No significant alterations were evidenced in LDL and cholesterol concentrations upon exercise. The decrease in PON1 activity became higher with increasing temperature whereas the elevation in MDA levels increased at 18°C. In the l-carnitine supplementation group, recovery in PON1 activity was observed significant at 28°C and very significant at 38°C. MDA concentration was almost the same with that of the non-carnitine group at 18 and 38°C, but it significantly decreased at 28°C. Considering the recovery in PON1 and MDA levels at 28°C, which is the temperature of the sedentary group; our results suggest that l-carnitine supplementation has a protective role on exhaustive exercise-induced oxidative stress. Findings of this study also demonstrate influences of thermal stress on these parameters during exhaustive exercise.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-07-01

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

  17. 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.

  18. Carnitine supplementation decreases capacitation-like changes of frozen-thawed buffalo spermatozoa.

    Science.gov (United States)

    Longobardi, Valentina; Salzano, Angela; Campanile, Giuseppe; Marrone, Raffaele; Palumbo, Francesco; Vitiello, Milena; Zullo, Gianluigi; Gasparrini, Bianca

    2017-01-15

    The aim of this study was to evaluate the effect of carnitine supplementation of semen extender on fertility parameters of frozen-thawed buffalo sperm. Buffalo semen was cryopreserved in BioXcell containing 0 (control group), 2.5 and 7.5-mM carnitine. After thawing, viability, motility, membrane integrity and capacitation status (assessed by localization of phosphotyrosine-containing proteins and chlortetracycline, chlortetracycline assay) were evaluated. Furthermore, total antioxidant capacity, reactive oxygen species (ROS) and lipid peroxidation levels, as well as adenosine triphosphate (ATP) content and phospholipids concentration were assessed. Finally, in vitro-fertilizing ability was evaluated after heterologous IVF. An increased post-thawing sperm motility and membrane integrity were recorded in both treated groups compared with the control (44.4 ± 3.5, 53.1 ± 3.9, and 52.5 ± 3.6%; P carnitine, respectively). Supplementation of carnitine to the freezing extender decreased (P carnitine). In agreement with this, carnitine also decreased (P carnitine). Interestingly, carnitine increased total antioxidant capacity and ATP content of buffalo frozen-thawed sperm (1.32 ± 0.02, 1.34 ± 0.01, 1.37 ± 0.01 mM/L and 4.1 ± 0.1, 5.3 ± 0.1 and 8.2 ± 0.4 nM × 10(8) sperm; P carnitine). Intracellular ROS decreased in carnitine-treated sperm compared with the control, as indicated by dihydroethidium (DHE) values (0.22 ± 0.01, 0.18 ± 0.01, and 0.14 ± 0.0 μM/100 μL dihydroethidium, respectively, with 0, 2.5-, and 7.5-mM carnitine; P carnitine improved buffalo sperm quality by increasing ATP generation and modulating ROS production, without affecting in vitro fertilizing ability.

  19. 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.

  20. Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise.

    Science.gov (United States)

    Seiler, Sarah E; Koves, Timothy R; Gooding, Jessica R; Wong, Kari E; Stevens, Robert D; Ilkayeva, Olga R; Wittmann, April H; DeBalsi, Karen L; Davies, Michael N; Lindeboom, Lucas; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B; Muoio, Deborah M

    2015-07-07

    Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance.

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

    Directory of Open Access Journals (Sweden)

    Abeer Hassan

    2015-01-01

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

  2. Effect of intravenous L-carnitine on growth parameters and fat metabolism during parenteral nutrition in neonates.

    Science.gov (United States)

    Helms, R A; Mauer, E C; Hay, W W; Christensen, M L; Storm, M C

    1990-01-01

    To determine whether intravenous carnitine can improve nutritional indices, neonates requiring parenteral nutrition were randomized into carnitine treatment (n = 23) and control (n = 20) groups. Observed plasma lipid indices, carnitine and nitrogen balances, and plasma carnitine concentrations were not different in the prestudy period. Under standardized, steady-state conditions, 0.5 g/kg Intralipid was administered intravenously over 2 hr prior to carnitine administration, after infants received 7 days of 50 mumol/kg/day, and after a second 7 days of 100 mumol/kg/day of continuous intravenous L-carnitine as part of parenteral nutrition. Triglyceride (TGY), free fatty acid (FFA), acetoacetate (AA), beta-hydroxybutyrate (BOB), and plasma carnitine concentrations were measured prior to and at 2, 4, and 6 hr after the initiation of the lipid bolus. Twenty-four-hour urine collections for nitrogen and carnitine balance were obtained on days 7 and 14. Neonates receiving carnitine had significantly greater concentrations of plasma carnitine on days 7 and 14 (p less than 0.001). Greater nitrogen (p less than 0.05) and carnitine (p less than 0.001) balances and weight gain (week 2, p less than 0.05) were found in the carnitine-supplemented group when compared with controls. On day 14, (BOB + AA)/FFA ratios were significantly higher (p less than 0.05), and peak TGY concentrations and 6-hr FFA concentrations were significantly lower (p less than 0.05) in the treatment group. Carnitine supplementation was associated with modest increases in growth and nitrogen accretion possibly by enhancing the neonate's ability to utilize exogenous fat for energy.

  3. Developmental regulation and modulation of apoptotic genes expression in sheep oocytes and embryos cultured in vitro with L-carnitine.

    Science.gov (United States)

    Mishra, A; Reddy, I J; Gupta, Psp; Mondal, S

    2016-12-01

    The objective of this study was to find out the impact of L-carnitine (10 mM) on developmental regulation of preimplantation sheep embryos cultured in vitro when supplemented in maturation medium and post-fertilization medium separately. Subsequent objective was to observe the L-carnitine-mediated alteration in expression of apoptotic genes (Bcl2, Bax, Casp3 and PCNA) in sheep oocytes and developing embryos produced in vitro. Oocytes matured with L-carnitine showed significantly (p carnitine during post-fertilization period. So it is suggested to use L-carnitine during maturation than post-fertilization period. Antiapoptotic and proliferative effects of L-carnitine were confirmed by inducing culture medium with actinomycin D (apoptotic agent) and TNFα (antiproliferative agent), respectively, with and without L-carnitine. Oocytes and embryos cultured with actinomycin D and TNFα showed developmental arrest with significant (p supplementation of L-carnitine to actinomycin D and TNFα induced culture medium showed similar result as that of control. L-carnitine supplementation during IVM significantly (p carnitine upregulated the expression of Bax in initial developmental stages but downregulated at latter part, whereas the expression of Casp3 was upregulated upto 16-cell stage but after that there was no difference in expression. Expression of GAPDH gene was not affected by L-carnitine supplementation. In conclusion, L-carnitine acted as an antiapoptotic and proliferative compound during embryo development and supplementation of L-carnitine during IVM altered the expression of apoptotic genes in the developmental stages of embryos.

  4. The reduction of heat production in exercising pigeons after L-carnitine supplementation.

    Science.gov (United States)

    Janssens, G P; Buyse, J; Seynaeve, M; Decuypere, E; De Wilde, R

    1998-04-01

    Four groups (CS,CR,PS,PR) of nine trained male racing pigeons were deprived of feed for 1 d and then subjected to a respiration chamber test in order to study the effect of oral 1-carnitine supplementation on the energy metabolism during flight. One week before, groups CS and CR were orally supplemented with 90 mg of 1-carnitine daily, whereas PS and PR were given a placebo. Groups CS and PS underwent flight simulation by electrostimulation of the breast muscles. Flight simulation increased heat production, kept respiratory quotient from decreasing, decreased thyroxine levels, and increased weight loss. L-Carnitine decreased the rise in heat production during electrostimulation but did not influence respiratory quotient, weight loss, or thyroid hormones. L-Carnitine supplementation in pigeons improves fatty acid combustion efficiency during heavy exercise.

  5. Cardiogenic shock and L-carnitine: clinical data and therapeutic perspectives.

    Science.gov (United States)

    Corbucci, G G; Lettieri, B

    1991-01-01

    Research experiences on the use of L-carnitine in conditions of acute hypoxia underline the protective role of this molecule on the cellular enzymic complex. To obtain unconfutable clinical data at this regard, the survival rate in two groups of patients affected by cardiogeic shock was evaluated. The first group (80 patients) was treated with L-carnitine while the second group (36 patients) received sodium bicarbonate. The results showed a significant response to L-carnitine treatment, indicating the role of this molecule on the metabolic acidosis due to shock. The sum of these data confirmed the role of L-carnitine in the reversible phase of cardiogenic shock in terms of enzymic protection in the course of cellular oxidative damage.

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

    Science.gov (United States)

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

    1995-12-01

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

  7. 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.

  8. Carnitine status of children receiving long-term total parenteral nutrition: a longitudinal prospective study.

    Science.gov (United States)

    Moukarzel, A A; Dahlstrom, K A; Buchman, A L; Ament, M E

    1992-05-01

    Nine children receiving carnitine-free total parenteral nutrition for 7.2 +/- 2.6 years since birth were prospectively studied for 3 years. Plasma values of total and free carnitine were 50% lower than those of age-matched healthy control subjects (p less than 0.02) but did not decrease further during the 3-year period. No significant abnormalities in free fatty acids, triglycerides, or cholesterol were found. The mean levels of alanine and aspartate aminotransferases and of alkaline phosphatase were slightly increased (p less than 0.02) at the initiation of the study but remained in the same range 3 years later. The low plasma carnitine values appeared to be without clinical consequence after 10 years of carnitine-free total parenteral nutrition.

  9. Effects of carnitine administration to multiple injury patients receiving total parenteral nutrition.

    Science.gov (United States)

    Testasecca, D

    1987-01-01

    Blood, urine and tissue concentrations of carnitine have been found to be below the normal values in patients receiving total parenteral nutrition (TPN). It might be postulated that the carnitine deficiency is responsible for the metabolic disturbances observed during TPN. To 20 patients (10 male and 10 female) in a state of coma following multiple injuries or brain injury and submitted to a TPN regimen (hypertonic polycarbohydrate, 7% aminoacid solutions on 10% lipid suspensions), we have administered 3-8 g/day of carnitine i.v. as a single bolus each morning. We have found no increase in cholesterol and triglycerides serum levels and a normalization of pyruvate and lactate serum levels. Our results seem to confirm the importance of carnitine in improving metabolism of the energy-giving substrate in patients receiving TPN.

  10. Carnitine supplementation modulates high dietary copper-induced oxidative toxicity and reduced performance in laying hens.

    Science.gov (United States)

    Güçlü, Berrin Kocaoğlu; Kara, Kanber; Çakır, Latife; Çetin, Ebru; Kanbur, Murat

    2011-12-01

    This experiment was conducted to evaluate the effects of L-carnitine on performance, egg quality and certain biochemical parameters in laying hens fed a diet containing high levels of copper proteinate. Forty-eight 42-week-old laying hens were divided into four groups with four replicates. The laying hens were fed with a basal diet (control) or the basal diet supplemented with either 400 mg carnitine (Car)/kg diet, 800 mg copper proteinate (CuP)/kg diet or 400 mg carnitine + 800 mg copper (Car+CuP)/kg diet, for 6 weeks. Supplemental CuP decreased feed consumption (p supplemental CuP and Car+CuP. Supplemental CuP caused an increase in plasma malondialdehyde (p carnitine and copper combination may prevent the possible adverse effects of high dietary copper on performance and lipid peroxidation in hens.

  11. Effects of breeder hen age and dietary L-carnitine on progeny embryogenesis.

    Science.gov (United States)

    Peebles, E D; Kidd, M T; McDaniel, C D; Tanksley, J P; Parker, H M; Corzo, A; Woodworth, J C

    2007-06-01

    1. Ross 308 broiler breeder hens were given diets containing 0 or 25 mg L-carnitine/kg (8 replications per treatment) from 21 weeks of age. 2. Hens were inseminated with semen from Ross broiler breeder males. In a common facility, subsequent progeny hatchability and embryonic mortality at 25, 30, 32, and 38 weeks of breeder age were evaluated. 3. Subsequent egg component weights, incubational egg water loss, progeny embryo growth, and embryo, yolk sac and liver composition through 18 d of incubation at 27, 32, and 38 weeks of breeder age were evaluated. 4. Calculated additions of L-carnitine were in agreement with analysed contents of 3.5 and 31.1 mg free L-carnitine/kg of diet, respectively, and total L-carnitine concentrations increased by 48.6, 21.7, and 10.0% in 0-d yolk, 18-d yolk sac, and 18-d liver samples, respectively, due to the addition of dietary L-carnitine. 5. Supplemental L-carnitine resulted in increased (0.6%) relative 0-d egg yolk weight across weeks 27, 32, and 38, and reduced (0.38%) 18-d yolk sac palmitoleic acid concentration at week 27 without altering embryogenesis. 6. In conclusion, dietary L-carnitine (25 mg/kg of the diet) was deposited in the yolks of broiler breeder hens and was subsequently transferred to the embryonic liver via yolk sac absorption through 18 d of incubation. Furthermore, dietary L-carnitine supplementation increased ovarian follicle yolk deposition in 27-, 32-, and 38-week-old breeder hens, and influenced yolk sac fatty acid beta-oxidation in embryos from 27-week-old breeder hens causing yolk sac palmitoleic acid concentrations to be reduced by 18 d of incubation.

  12. The effects of L-carnitine administration on energy metabolism in pregnant Halep (Damascus) goats

    OpenAIRE

    KAÇAR, Cihan; ZONTURLU, Abuzer Kaffar; KARAPEHLİVAN, Mahmut

    2010-01-01

    The aim of this study was to determine the effects of parenteral administration of L-carnitine on some biochemical parameters in Halep (Damascus) goats during the last month of pregnancy. L-carnitine was administrated to goats in group I (n = 13) by subcutaneous injections once a week during the last month of the pregnancy. Physiologic salt solution was administered to goats in group II (n = 12) by the same route during the same period. Differences of glucose concentration between groups were...

  13. The effect of L-carnitine-supplemented total parenteral nutrition on tissue amino acid concentrations in piglets.

    Science.gov (United States)

    Böhles, H; Michalk, D; Brandl, U; Fekl, W; Börresen, H C; Stehr, K

    1984-04-01

    Miniature piglets underwent total parenteral nutrition (TPN) with and without L-carnitine supplementation during a 7-day period. Thereafter the tissue amino acid concentrations of liver, heart, skeletal muscle and brain were determined and compared to those of orally fed animals. The altered tissue amino acid concentrations during TPN without carnitine returned to normal when L-carnitine was supplemented. The most striking changes of tissue concentrations showed taurine in liver, muscle and brain and ethanolamine in heart and brain. In muscle the branched-chain amino acids were increased when L-carnitine was added to the TPN regime. Ethanolamine changes were discussed with respect to the position of this amino acid in the synthesis of phospholipids. The marked decrease of brain taurine concentrations after carnitine-free TPN was accompanied by reduced values for GABA. Both the substances function as inhibitory transmitters in the brain and should be considered when seizure activity in patients with systemic carnitine deficiency is discussed.

  14. Nutritional support and cardioprotection with L-carnitine: prescription appropriateness and safety concerns in Mexican neonates.

    Science.gov (United States)

    Gómez-Oliván, Leobardo Manuel; Valdés-Alanis, Analleli; Castro-Pastrana, Lucila I; Galar-Martinez, Marcela; Romero-Castillo, Carolina Angélica

    2011-01-01

    Medication errors are probably more common in neonates than is generally appreciated. In Mexican pediatric hospitals, L-carnitine is mainly used for nutritional support and to treat cardiomyopathy secondary to neonatal asphyxia. Using a longitudinal-retrospective approach we assessed the appropriateness of all L-carnitine prescriptions written during a 12-month period at a NICU of a second-level hospital located in Toluca, Mexico. Reports of adverse reactions possibly related to L-carnitine therapy were collected and characterized. Overall, administration of L-carnitine was considered justified and appropriate only in 18% of patients. 60.7% of L-carnitine prescriptions were rated as inappropriate because the prescribed doses fell outside the recommendations. The overall rate of ADRs calculated from the patient population was 18.03%. All of them were of gastrointestinal type: abdominal cramps (8 cases, 61.54%) and vomiting (5 cases, 38.46%). Our results supported the establishment of an L-carnitine rational use policy at the NICU of the hospital under study.

  15. 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.

  16. Influence of dietary carnitine in growing sheep fed diets containing non-protein nitrogen.

    Science.gov (United States)

    Chapa, A M.; Fernandez, J M.; White, T W.; Bunting, L D.; Gentry, L R.; Lovejoy, J C.; Owen, K Q.

    2001-04-01

    The influence of supplemental L-carnitine was investigated in growing sheep fed rations containing non-protein nitrogen (NPN). The experiment was conducted as a randomized block design with a 2x2 factorial arrangement of treatments. Lambs (77.4kg BW, n=24) were fed a total mixed ration (12.1-13.6% CP) with two levels of L-carnitine (0 or 250ppm) and two levels of NPN (urea contributing 0 or 50% of total dietary N) for a 50-day period. Jugular blood samples were collected at 0, 1, and 3h post-feeding, and ruminal fluid samples were collected at 1h post-feeding, during days 1, 8, 29, and 50 of the experiment. Average daily gain (121 versus 214g) was lower (P0.10) from the control group. Plasma urea N levels in both OULT 1 and OULT 2 were lower (P<0.0001) in the NPN and NPN with L-carnitine groups compared with the control and L-carnitine groups. In the present experiment, production and plasma criteria were affected by NPN incorporation in the diets. Production criteria were not affected by inclusion of L-carnitine in the diet, however, L-carnitine reduced experimentally induced hyperammonemia by day 50 of the trial.

  17. Effect of propionyl-L-carnitine on oscillatory potentials in electroretinogram in streptozotocin-diabetic rats.

    Science.gov (United States)

    Hotta, N; Koh, N; Sakakibara, F; Nakamura, J; Hamada, Y; Hara, T; Fukasawa, H; Kakuta, H; Sakamoto, N

    1996-09-12

    The effect of propionyl-L-carnitine, an analogue of L-carnitine, and insulin on the oscillatory potentials of the electroretinogram was determined in rats with streptozotocin-induced diabetes. Propionyl-L-carnitine was administered at a daily dose of 0.5 g/kg by gavage for 4 weeks, while other rats were treated with subcutaneous injections of insulin (8-10 U/day). Both treatments shortened the peak latencies of the oscillatory potentials in the electroretinogram, which were significantly prolonged in untreated diabetic rats (O1, O2 and O3, and sigma (O1 + O2 + O3)) (P carnitine level in diabetic rats was prevented by both treatments. Insulin produced a significant reduction of retinal glucose, sorbitol and fructose levels in diabetic rats, while propionyl-L-carnitine failed to do so. However, both treatments markedly reduced serum lipids levels in the diabetic rats. These findings provide information on the pathogenesis of diabetic retinopathy as well as suggesting the potential therapeutic value of propionyl-L-carnitine for retinopathy.

  18. Doxorubicin toxicity can be ameliorated during antioxidant L-carnitine supplementation.

    Science.gov (United States)

    Alshabanah, Othman A; Hafez, Mohamed M; Al-Harbi, Mohamed M; Hassan, Zeinab K; Al Rejaie, Salim S; Asiri, Yosef A; Sayed-Ahmed, Mohamed M

    2010-01-01

    Doxorubicin is an antibiotic broadly used in treatment of different types of solid tumors. The present study investigates whether L-carnitine, antioxidant agent, can reduce the hepatic damage induced by doxorubicin. Male Wistar albino rats were divided into six groups: group 1 were intraperitoneal injected with normal saline for 10 consecutive days; group 2, 3 and 4 were injected every other day with doxorubicin (3 mg/kg, i.p.), to obtain treatments with cumulative doses of 6, 12, and 18 mg/kg. The fifth group was injected with L-carnitine (200 mg/kg, i.p.) for 10 consecutive days and the sixth group was received doxorubicin (18 mg/kg) and L-carnitine (200 mg/kg). High cumulative dose of doxorubicin (18 mg/kg) significantly increase the biochemical levels of alanine transaminase , alkaline phosphatase, total bilirubin, total carnitine, thiobarbituric acid reactive substances (TBARs), total nitrate/nitrite (NOx) p carnitine supplementation completely reverse the biochemical and gene expression levels induced by doxorubicin to the control values. In conclusion, data from this study suggest that the reduction of antioxidant defense during doxorubicin administration resulted in hepatic injury could be prevented by L-carnitine supplementation by decreasing the oxidative stress and preserving both the activity and gene expression level of antioxidant enzymes.

  19. Effects of L-carnitine administration on mitochondrial electron transport activity present in human muscle during circulatory shock.

    Science.gov (United States)

    Corbucci, G G; Gasparetto, A; Antonelli, M; Bufi, M; Crimi, G; Conti, G; De Blasi, R A; Candiani, A; Cooper, M B; Jones, D A

    1985-01-01

    Carnitine was administered to a group of patients in shock, and the activities of cytochrome oxidase and succinate cytochrome c reductase in muscle needle biopsies from these patients were compared to those activities present in a non-carnitine treated control group of patients. Carnitine seemingly exerted a significant protective action on cytochrome oxidase activity during the initial phases of shock, but not to such an extent on succinate cytochrome c reductase activities.

  20. 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.

  1. Effects of L-carnitine supplemented total parenteral nutrition on lipid and energy metabolism in postoperative stress.

    Science.gov (United States)

    Pichard, C; Roulet, M; Rössle, C; Chiolero, R; Schutz, Y; Temler, E; Boumghar, M; Schindler, C; Zurlo, F; Jéquier, E

    1988-01-01

    During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were divided randomly in two equal isonitrogenous groups (0.2 g/kg.day). Both received TPN (35 kcal/kg.day; equally provided as long-chain triglycerides and glucose) over 11 days without (group A) and with (group B) L-carnitine supplementation (12 mg/kg.day = 75 mumol/kg.day). Compared with healthy controls, the total body carnitine pool prior to the operation was significantly reduced in both groups, suggesting a state of semistarvation and muscle wasting. In group A the plasma levels of total carnitine and its subfractions (free carnitine, short- and long-chain acylcarnitine) remained stable during the study whereas in group B the total plasma carnitine concentration rose mainly due to an increase in free carnitine. In group A the cumulative urinary carnitine losses were 11.5 +/- 2.6 mmol (= 15.5 +/- 3.1% of the estimated total body carnitine pool). In group B 3.1 +/- 1.9 mmol (= 11.1 +/- 7.6%) of the infused carnitine was retained in the immediate postoperative phase until day 6, but this amount was completely lost at completion of the study period. No significant differences in the respiratory quotient or in the plasma levels of triglycerides, free fatty acids, and ketone bodies were observed, between or within the groups, before the operation and after 11 days of treatment. It is concluded that the usefulness of carnitine supplementation during postoperative TPN was not apparent in the present patient material.

  2. Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats.

    Science.gov (United States)

    Cahova, Monika; Chrastina, Petr; Hansikova, Hana; Drahota, Zdenek; Trnovska, Jaroslava; Skop, Vojtech; Spacilova, Jana; Malinska, Hana; Oliyarnyk, Olena; Papackova, Zuzana; Palenickova, Eliska; Kazdova, Ludmila

    2015-03-01

    The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.

  3. The adverse effects of long-term l-carnitine supplementation on liver and kidney function in rats.

    Science.gov (United States)

    Liu, L; Zhang, D-M; Wang, M-X; Fan, C-Y; Zhou, F; Wang, S-J; Kong, L-D

    2015-11-01

    Levo-Carnitine (l-carnitine) is widely used in health and food. This study was to focus on the adverse effects of 8-week oral supplementation of l-carnitine (0.3 and 0.6 g/kg) in female and male Sprague Dawley rats. l-carnitine reduced body and fat weights, as well as serum, liver, and kidney lipid levels in rats. Simultaneously, hepatic fatty acid β-oxidation and lipid synthesis were disturbed in l-carnitine-fed rats. Moreover, l-carnitine accelerated reactive oxygen species production in serum and liver, thereby triggering hepatic NOD-like receptor 3 (NLRP3) inflammasome activation to elevate serum interleukin (IL)-1β and IL-18 levels in rats. Alteration of serum alkaline phosphatase levels further confirmed liver dysfunction in l-carnitine-fed rats. Additionally, l-carnitine may potentially disturb kidney function by altering renal protein levels of rat organic ion transporters. These observations may provide the caution information for the safety of long-term l-carnitine supplementation.

  4. The effect of L-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients.

    Science.gov (United States)

    Suchitra, M M; Ashalatha, V L; Sailaja, E; Rao, A Madhusudhana; Reddy, V Sheshadri; Bitla, Aparna R; Sivakumar, V; Rao, P V L N Srinivasa

    2011-11-01

    Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD) patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L-Carnitine supplementation may have potential benefits in improving dialysis-related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP), total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group.

  5. Supplementation of culture medium with L-carnitine improves development and cryotolerance of bovine embryos produced in vitro.

    Science.gov (United States)

    Takahashi, Toshikiyo; Inaba, Yasushi; Somfai, Tamas; Kaneda, Masahiro; Geshi, Masaya; Nagai, Takashi; Manabe, Noboru

    2013-01-01

    High lipid content in embryos is associated with low freezing tolerance. This study assessed the effects of exogenous L-carnitine, an enhancer of lipid metabolism, on the in vitro development and freezing survival of bovine embryos. Also, effects on metabolic activity, reactive oxygen species (ROS) and apoptosis were investigated. Supplementation of embryo culture medium with 1.518 mM or 3.030 mM L-carnitine significantly increased the rates of zygote development to the blastocyst stage and blastocyst cell numbers whereas 6.072 mM of this compound did not improve embryo development. Survival rates after slow freezing of blastocysts were significantly higher when embryos were cultured in the presence of 1.518 mM or 3.030 mM L-carnitine compared with the control. A lower density of lipid droplets was detected in L-carnitine-treated blastocysts compared with the control. L-carnitine significantly reduced ROS levels in 2-cell embryos but did not reduce ROS levels at later stages. The apoptotic cell rate was not different between control and L-carnitine-treated blastocysts. L-carnitine significantly increased ATP levels in 2-cell embryos but not at the 8-cell or blastocyst stages. L-carnitine increased the expression of metabolism-related ATP6 and COX1 genes in blastocysts. In conclusion, L-carnitine supplementation enhanced lipid metabolism in embryos resulting in improved development and cryotolerance of bovine blastocysts produced in vitro.

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

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    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.

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

    Science.gov (United States)

    Savica, V; Bellinghieri, G; Lamanna, F

    1992-01-01

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

  8. Effects of L-carnitine and L-acetyl-carnitine on testicular sperm motility and chromatin quality

    Directory of Open Access Journals (Sweden)

    Elham Aliabadi

    2012-01-01

    Full Text Available Background: Sperm cells extracted from testes (TESE have poor chromatin quality and motility. Various substances are used in the laboratory to increase sperm motility and improve the ART outcomes; however, there are few research which considered improving both sperm motility and chromatin quality. Objective: The aim of this investigation was to evaluate the improvement of the testicular sperm motility and chromatin quality exposed to L-carnitine (LC and L-acetyl-carnitine (LAC, which are normally concentrated in testis and epididymis, compared with Pentoxifylline (PF, which used for sperm motility enhancement in IVF procedures. Materials and Methods: TESE samples from 30 male mice divided into four parts. The sperm samples were added to Ham' F10 (control or the media contained 1.76mM of LC, LAC or PF, then, the samples were kept in the room temperature for 30, 90 and 180 min. At each time step, sperm motility and chromatin quality were assessed. Chromatin quality was evaluated by chromomycin A3 and aniline blue. Statistical analysis was performed using one way analysis of variance (ANOVA. A p-value less than 0.05 were accepted as a statistically significant difference. Results: The results showed LC, LAC and PF significantly increased the sperm motility. However, sperm chromatin quality only improved significantly by administration of LC and LAC. Conclusion: Administration of LC and LAC to the testicular sperm samples can lead to improve both sperm motility and chromatin quality. It may be because they can mimic in vivo sperm condition during late spermatogenesis.

  9. Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico.

    Science.gov (United States)

    Colonna, P; Iliceto, S

    2000-02-01

    Left ventricular dilatation after acute myocardial infarction (MI) is a powerful predictor of progressive functional deterioration, culminating in heart failure and death. The most important determinants of post-MI left ventricular remodeling are the size of the infarct, the degree of residual stenosis in the infarct-related artery, and the viability of the infarct zone. In addition to reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may represent a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function. Ongoing studies with early metabolic intervention with carnitine in the acute phase of infarction may prove successful in protecting the microcirculation against ischemic damage and enhancing its ability to respond to blood flow resumption. The results of the multicenter, randomized, double-blind Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial suggest that the early and long-term administration of L-carnitine attenuates progressive left ventricular dilatation after acute anterior MI. Results show significant, consistent reductions in end-diastolic volume and end-systolic volume in patients who received L-carnitine compared with placebo. The ongoing CEDIM-2 trial (projected 4000 patients with acute MI) will assess the efficacy of L-carnitine in reducing the combined incidence of death and heart failure at 6 months. In addition to standard reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may be a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function by limiting infarct size, decreasing residual stenosis in the infarct-related artery, and increasing viability of the infarct zone.

  10. 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.

  11. Treatment with Carnitine Enhances Bone Fracture Healing under Osteoporotic and/or Inflammatory Conditions.

    Science.gov (United States)

    Aydin, Ali; Halici, Zekai; Albayrak, Abdulmecit; Polat, Beyzagul; Karakus, Emre; Yildirim, Omer Selim; Bayir, Yasin; Cadirci, Elif; Ayan, Arif Kursad; Aksakal, Ahmet Murat

    2015-09-01

    The aim of this study was to examine the effects of carnitine on bone healing in ovariectomy (OVX) and inflammation (INF)-induced osteoporotic rats. The rats were randomly divided into nine groups (n = 8 animals per group): sham-operated (Group 1: SHAM); sham + magnesium silicate (Mg-silicate) (Group 2: SHAM + INF); ovariectomy (Group 3: OVX); ovariectomy + femoral fracture (Group 4: OVX + FRC); ovariectomy + femoral fracture + Mg-silicate (Group 5: OVX + FRC + INF); ovariectomy + femoral fracture + carnitine 50 mg/kg (Group 6: OVX + FRC + CAR50); ovariectomy + femoral fracture + carnitine 100 mg/kg (Group 7: OVX + FRC + CAR100); ovariectomy + femoral fracture + Mg-silicate + carnitine 50 mg/kg (Group 8: OVX + FRC + INF + CAR50); and ovariectomy + femoral fracture + Mg-silicate + carnitine 100 mg/kg (Group 9: OVX + FRC + INF + CAR100). Eight weeks after OVX, which allowed for osteoporosis to develop, INF was induced with subcutaneous Mg-silicate. On day 80, all of the rats in groups 4-9 underwent fracture operation on the right femur. Bone mineral density (BMD) showed statistically significant improvements in the treatment groups. The serum markers of bone turnover (osteocalcin and osteopontin) and pro-inflammatory cytokines (tumour necrosis factor α, interleukin 1β and interleukin 6) were decreased in the treatment group. The X-ray images showed significantly increased callus formation and fracture healing in the groups treated with carnitine. The present results show that in a rat model with osteoporosis induced by ovariectomy and Mg-silicate, treatment with carnitine improves the healing of femur fractures.

  12. Carnitine deprivation adversely affects cardiovascular response to bacterial endotoxin (LPS) in the anesthetized neonatal pig.

    Science.gov (United States)

    Penn, D; Zhang, L; Bobrowski, P J; Quinn, M; Liu, X; McDonough, K H

    1998-11-01

    Sepsis and endotoxemia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine. To investigate whether carnitine deprivation affects the neonate's ability to respond to endotoxin, 19 newborn piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN-) or supplemented (CARN+) with L-carnitine (400 mg/L). Cardiovascular performance, i.e., heart rate; blood pressure (BP); cardiac output (CO); systemic vascular resistance (SVR), and metabolic response, i.e., plasma glucose; lactate; tumor necrosis factor alpha; tissue nitric oxide; and urinary nitrites, were studied serially in anesthetized piglets for 3 h after endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or vehicle administration. Plasma and tissue carnitine values were lower in CARN- than in CARN+ piglets. Prior to LPS, no differences were found for most parameters (excepting lower diastolic BP and SVR in CARN- animals). Systolic, diastolic, and mean BP fell after LPS but recovered by the end of the experiment. Nadirs were lower in CARN- than in CARN+ piglets. CO tended to be higher in CARN- than in CARN+ animals and fell after LPS. SVR fell after LPS and was lower in CARN- than in CARN+ piglets. LPS-treated animals transiently increased urinary flow. By all measures (plasma tumor necrosis factor alpha, glucose and lactate, tissue nitric oxide, and urinary nitrite excretion), LPS provocation was similar for both groups. Chronologically, BP changes were more closely related to SVR than to CO. Our findings suggest that carnitine deprivation diminishes tissue carnitine concentrations and adversely affects cardiovascular response to LPS, in part mediated by the peripheral vasculature.

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

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    Babak Hosseintabar

    2015-09-01

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

  14. Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects.

    Science.gov (United States)

    Tabei, Seyed Mohammad Bagher; Mazloom, Maryam; Shahriari, Mahdi; Zareifar, Soheila; Azimi, Ali; Hadaegh, Amirhossein; Karimi, Mehran

    2013-11-01

    Beta-thalassemia minor (BTM) patients usually experience fatigue, bone pain complaint, and muscle weakness. Carnitine is an essential protein for transportation of long-chain fatty acids to the matrix for beta-oxidation. BTM patients have abnormally low plasma carnitine concentrations, which results in deficient ATP production. Carnitine and folic acid together may have a role in preventing bone pain complaint and fatigue in these patients. The aim of this study is to determine the effect of carnitine and folic acid supplementation in subjects with BTM. Seventy three BTM (mean age 11.06 ± 5.46 years) and 23 healthy controls (mean age 8.48 ± 3.78 years) were enrolled in the study. Fasting blood was drawn to determine baseline free and total carnitine levels, red blood cell folate concentration, and hemoglobin level. BTM were divided into three groups and received different types of supplementation for 3 months: Group 1, 50 mg/kg/day carnitine; Group 2, 50 mg/kg/day carnitine plus 1 mg/day folic acid; and Group 3, 1 mg/day folic acid. Controls did not receive supplementation. Laboratory parameters were again evaluated after 3 months' supplementation. A detailed quality of life questionnaire was designed to investigate muscle symptoms before and after supplementation. Free and total plasma carnitine concentration and hemoglobin levels in BTM subjects increased significantly after carnitine supplementation (P carnitine. Red blood cell folate level increased after folic acid supplementation. Carnitine and folic acid supplementation resulted in a decrease in bone pain complaint and muscle weakness in cases with β-thalassemia minor.

  15. 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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    1994-01-01

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

  18. Inhibition of Gene Expression of Organic Cation/Carnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models

    Directory of Open Access Journals (Sweden)

    Mohamed M. Sayed-Ahmed

    2012-01-01

    Full Text Available It is well documented that high therapeutic doses of oxazaphosphorines, cyclophosphamide (CP and ifosfamide (IFO, are associated with cardiomyopathy. This study investigated whether oxazaphosphorines alter the expression of organic cation/carnitine transporter (OCTN2 and antioxidant genes and if so, whether these alterations contribute to CP and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of six treatment groups namely, control, L carnitine, CP, IFO, CP plus L carnitine and IFO plus L carnitine. In cardiac and kidney tissues, CP and IFO significantly decreased mRNA and protein expression of OCTN2. Oxazaphosphorines significantly increased serum acyl-carnitine/free carnitine ratio and urinary carnitine excretion and significantly decreased total carnitine in cardiac tissues. Interestingly, carnitine supplementation completely reversed the biochemical and gene expression changes-induced by oxazaphosphorines to the control values, except OCTN2 expression remained inhibited by IFO. Data from this study suggest that: (1 Oxazaphosphorines decreased myocardial carnitine content following the inhibition of OCTN2 mRNA and protein expression in cardiac tissues. (2 Oxazaphosphorine therapy increased urinary loss of carnitine secondary to the inhibition of OCTN2 mRNA and protein expression in proximal tubules of the kidney. (3 Carnitine supplementation attenuates CP but not IFO-induced inhibition of OCTN2 mRNA and protein expression in heart and kidney tissues.

  19. Neuroprotective effects of L-carnitine against oxygenglucose deprivation in rat primary cortical neurons

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    Yu Jin Kim

    2012-07-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD. &lt;b&gt;Methods:&lt;/b&gt; Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO and propidium iodide (PI were counted, and lactate dehydrogenase (LDH activity and reactive oxygen species (ROS levels were measured. The 3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 μM, 10 μM, and 100 μM on OGD-induced neurotoxicity. &lt;B&gt;Results:&lt;/b&gt; Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 μM and 100 μM of L-carnitine compared with the untreated OGD group (P&lt;0.05. The application of L-carnitine at 100 μM significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P&lt;0.05. &lt;B&gt;Conclusion:&lt;/b&gt; L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

  20. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Science.gov (United States)

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Newborn screening test system for amino acids... carnitine, and acyl-carnitine metabolism. (b) Classification. Class II (special controls). The...

  1. Supplementation with carnitine reduces the severity of constipation: a retrospective study of patients with severe motor and intellectual disabilities.

    Science.gov (United States)

    Murata, Shinya; Inoue, Keisuke; Aomatsu, Tomoki; Yoden, Atsushi; Tamai, Hiroshi

    2017-03-01

    Carnitine is an essential nutrient for the mitochondrial transport of fatty acids. Carnitine deficiency causes a variety of symptoms in multiple organs. Patients with severe motor and intellectual disabilities often have carnitine deficiency. This study aimed to determine the correlation between constipation and carnitine deficiency in them. Patients with severe motor and intellectual disabilities at our hospital were retrospectively reviewed. The correlation between level of free carnitine and severity of constipation was examined. Constipation and non-constipation groups were compared for age; sex; body mass index; bed rest period; use of anti-epileptic drugs, valproate sodium, or enteral nutrition; and serum levels of albumin, pre-albumin, totalcholesterol, free carnitine, folic acid, and trace elements. Moreover, severity of constipation before and after carnitine supplementation was assessed. Twenty-seven patients were enrolled. Of these, 14 were assigned to the constipation group and 13 to the non-constipation group. The free carnitine level was significantly correlated with severity of constipation (R = 0.7604, pcarnitine was significantly lower in the constipation compared with the non-constipation group (pcarnitine supplementation (pcarnitine supplementation could reduce the severity of constipation.

  2. 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.

  3. Role of Carnitine Acetyl Transferase in Regulation of Nitric Oxide Signaling in Pulmonary Arterial Endothelial Cells

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    Stephen M. Black

    2012-12-01

    Full Text Available Congenital heart defects with increased pulmonary blood flow (PBF result in pulmonary endothelial dysfunction that is dependent, at least in part, on decreases in nitric oxide (NO signaling. Utilizing a lamb model with left-to-right shunting of blood and increased PBF that mimics the human disease, we have recently shown that a disruption in carnitine homeostasis, due to a decreased carnitine acetyl transferase (CrAT activity, correlates with decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that the CrAT enzyme plays a major role in regulating NO signaling through its effect on mitochondrial function. We utilized the siRNA gene knockdown approach to mimic the effect of decreased CrAT activity in pulmonary arterial endothelial cells (PAEC. Our data indicate that silencing the CrAT gene disrupted cellular carnitine homeostasis, reduced the expression of mitochondrial superoxide dismutase-and resulted in an increase in oxidative stress within the mitochondrion. CrAT gene silencing also disrupted mitochondrial bioenergetics resulting in reduced ATP generation and decreased NO signaling secondary to a reduction in eNOS/Hsp90 interactions. Thus, this study links the disruption of carnitine homeostasis to the loss of NO signaling observed in children with CHD. Preserving carnitine homeostasis may have important clinical implications that warrant further investigation.

  4. Alterations in the carnitine cycle in a mouse model of Rett syndrome

    Science.gov (United States)

    Mucerino, Sabrina; Di Salle, Anna; Alessio, Nicola; Margarucci, Sabrina; Nicolai, Raffaella; Melone, Mariarosa A. B.; Galderisi, Umberto; Peluso, Gianfranco

    2017-01-01

    Rett syndrome (RTT) is a neurodevelopmental disease that leads to intellectual deficit, motor disability, epilepsy and increased risk of sudden death. Although in up to 95% of cases this disease is caused by de novo loss-of-function mutations in the X-linked methyl-CpG binding protein 2 gene, it is a multisystem disease associated also with mitochondrial metabolic imbalance. In addition, the presence of long QT intervals (LQT) on the patients’ electrocardiograms has been associated with the development of ventricular tachyarrhythmias and sudden death. In the attempt to shed light on the mechanism underlying heart failure in RTT, we investigated the contribution of the carnitine cycle to the onset of mitochondrial dysfunction in the cardiac tissues of two subgroups of RTT mice, namely Mecp2+/− NQTc and Mecp2+/− LQTc mice, that have a normal and an LQT interval, respectively. We found that carnitine palmitoyltransferase 1 A/B and carnitine acylcarnitine translocase were significantly upregulated at mRNA and protein level in the heart of Mecp2+/− mice. Moreover, the carnitine system was imbalanced in Mecp2+/− LQTc mice due to decreased carnitine acylcarnitine transferase expression. By causing accumulation of intramitochondrial acylcarnitines, this imbalance exacerbated incomplete fatty acid oxidation, which, in turn, could contribute to mitochondrial overload and sudden death. PMID:28150739

  5. Plasma carnitine concentration and lipid metabolism in infants receiving parenteral nutrition.

    Science.gov (United States)

    Christensen, M L; Helms, R A; Mauer, E C; Storm, M C

    1989-11-01

    The relationships among plasma total carnitine concentration, postnatal age, and fatty acid metabolism were evaluated in 57 infants receiving parenteral nutrition. Concentrations of plasma carnitine, triglycerides, free fatty acids, acetoacetate, and beta-hydroxybutyrate were determined before and at 2 and 4 hours from the beginning of a standardized 2-hour lipid infusion. Plasma carnitine concentrations declined with increasing postnatal age. There were no significant differences in gestational age or triglyceride concentrations between infants less than or equal to 4 weeks of age and those greater than 4 weeks of age, whereas free fatty acid concentrations were lower and acetoacetate and beta-hydroxybutyrate concentrations were higher in the younger infants. Infants less than or equal to 4 weeks of age were further grouped according to plasma carnitine concentration greater than 13 nmol/ml (group 1) and less than or equal to 13 nmol/ml (group 2) and were then compared with infants greater than 4 weeks of age (group 3). There were no significant differences in triglyceride concentrations among the three groups; free fatty acids, acetoacetate, and beta-hydroxybutyrate concentrations for group 2 patients were similar to those of group 1 patients or fell between values for group 1 and group 3 patients. These results demonstrate decreasing plasma carnitine concentrations and possibly for more than 4 weeks.

  6. Carnitine supplementation effects on nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress.

    Science.gov (United States)

    Bucioli, Sérvio A; De Abreu, Luiz C; Valenti, Vitor E; Vannucchi, Helio

    2012-06-01

    Previous studies have demonstrated that exercise stress increases oxidative stress in rats. However, antioxidant supplement therapy effects on reactive oxygen substances are conflicting. We evaluated the effects of carnitine on renal nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress. Wistar rats were divided into 3 groups: (a) control group (not submitted to exercise stress), (b) exercise stress group, and (c) exercise stress and carnitine group. The rats from group 3 were treated with gavage administration of 1 ml of carnitine (5 mg·kg⁻¹) for 7 consecutive days. The animals from groups 2 and 3 were submitted to a bout of swimming exhaustive exercise stress. Kidney samples were analyzed for reactive substances to thiobarbituric acid by malondialdehyde (MDA), reduced glutathione (GSH), and vitamin-E levels. Carnitine treatment attenuated MDA increase caused by exercise stress (1: 0.16 ± 0.02 vs. 2: 0.34 ± 0.07 vs. 3: 0.1 ± 0.01 mmmol per milligram of protein; p carnitine improved oxidative stress and partially improved the nonenzymatic antioxidant activity in young rats submitted to exhaustive exercise stress.

  7. 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.

  8. Carnitine uptake by AGP2 in yeast Saccharomyces cerevisiae is dependent on Hog1 MAP kinase pathway.

    Science.gov (United States)

    Lee, Jiyoung; Lee, Boyoung; Shin, Dongjin; Kwak, Sang-Soo; Bahk, Jeong Dong; Lim, Chae Oh; Yun, Dae-Jin

    2002-06-30

    The AGP2 gene encodes a plasma membrane carnitine transporter in S. cerevisiae. Here, we report the identification of AGP2 as an osmotic stress response gene. AGP2 was isolated from mTn3 tagged mutants that contained in-frame fusions with lacZ. The expression of AGP2 was down-regulated by osmotic stresses, including NaCl, sorbitol, and KCI. We also found that carnitine uptake was inhibited by NaCl. In the ssk1delta stelldelta double-mutant strain, the expression of AGP2 and the uptake of carnitine were greatly reduced compared to the wild-type strain. Furthermore, carnitine uptake was inhibited by the constitutive expression of PBS2, which encodes a MAPKK that activates Hog1. We concluded, therefore, that the HOG pathway plays an important role in the regulation of carnitine uptake in S. cerevisiae.

  9. Carnitine supplementation and ketogenesis by small-for-date neonates on medium-and long-chain fatty acid formulae.

    Science.gov (United States)

    Labadaridis, J; Mavridou, I; Sarafidou, G; Alexiou, N; Costalos, C; Michelakakis, H

    2000-01-01

    Carnitine is a key molecule in energy production from various substrates. Although it is generally believed that it plays no role in the metabolism of medium-chain triglycerides, quite a few data exist to the contrary. In the present study we investigated the effect of carnitine on ketogenesis in small-for-date neonates fed formulae of equal caloric value and fat content that was predominantly long-chain triglycerides or medium-chain triglycerides (46% of total fat). According to our results there was a statistically significant interaction between carnitine and the chain length of the administered fat with respect to ketone production. Increased ketogenesis was only shown by the neonates receiving medium-chain triglycerides and carnitine. Our results provide further evidence for the involvement of carnitine in medium-chain triglyceride metabolism.

  10. 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.

  11. The metabolic effects of oral L-carnitine administration in infants receiving total parenteral nutrition with fat.

    Science.gov (United States)

    Coran, A G; Drongowski, R A; Baker, P J

    1985-12-01

    beta-Oxidation, an important pathway in the metabolism of free fatty acids, occurs within the mitochondria in mammals. L-Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane. Maintenance of normal carnitine concentrations in whole blood and tissues, either through diet or biosynthesis, would appear necessary for adequate utilization of fat as an energy source. Infants, especially premature ones, without an exogenous dietary source of carnitine, have decreased plasma carnitine levels compared with infants receiving carnitine-supplemented feedings. To determine the importance of carnitine supplementation in a total parenteral nutrition program in infants in which a fat emulsion serves as a major calorie source, the following study was undertaken. Twelve infants receiving total parenteral nutrition (TPN) with fat for seven days were divided into two treatment groups. Group 1 was orally supplemented for seven days with carnitine (70 mumol/l/kg/24 h in 24 mL of 5% dextrose), while the second group received seven days of placebo supplementation (dextrose 5%, 24 cc/24 h). Plasma carnitine levels in the carnitine-supplemented group were significantly higher (29 +/- 8 nmol/mL) than in the control group (12.4 +/- 3.5 nmol/mL) after seven days of treatment. However, clearance of serum triglycerides and free fatty acids was not significantly different between the two groups. Baseline triglyceride levels in the carnitine-supplemented group were 96 +/- 42 mg/dL, increased to 242 +/- 101 mg/dL after the lipid challenge and decreased to 121 +/- 47 mg/dL two hours after the lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Two cases of valproic acid poisoning treated with L-carnitine.

    Science.gov (United States)

    Chan, Y C; Tse, M L; Lau, F L

    2007-12-01

    Two cases of acute valproic acid poisoning with central nervous system depression and raised ammonia level without hepatotoxicity were reported. They were treated successfully with the use of the antidotes: L-carnitine and other supportive measures. Clinical manifestation and progress was described, and discussion is focused on the use of L-carnitine in valproic acid-induced hyperammonemia, from its mechanism to the clinical experiences in the literature. Based on the favorable response of our two cases and the literature review, we recommend the administration of intravenous L-carnitine in patients of valproic acid overdose with hyperammonemia or valproic acid-induced hyperammonemic encephalopathy and hepatotoxicity at a dose of 50 mg/kg every 8 h for the first initial 24 h with further individual assessment.

  13. L-carnitine in cardiogenic shock therapy: pharmacodynamic aspects and clinical data.

    Science.gov (United States)

    Corbucci, G G; Loche, F

    1993-01-01

    Following our previous work on biochemical and clinical aspects of cardiogenic shock, we carried out an open study on 27 patients hospitalized in shock condition and investigated for the entire period of permanence in intensive care units (ICU). The subjects were treated with high doses of L-carnitine following previous results on the use of this molecule in conditions of oxidative damage due to acute cellular hypoxia. When compared with the data reported in the literature, the results obtained in this study show a surprisingly positive trend for the carnitine-treated patients in terms of survival rate to the cardiogenic shock. This finding and statistical analysis of the clinical parameters confirm the suggestion that L-carnitine could be credited with a new and interesting role in the therapy of cardiogenic shock.

  14. 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.

  15. Carnitine Deficiency as the Possible Etiology of Idiopathic Mitral Valve Prolapse

    Science.gov (United States)

    Trivellato, Mario; De Palo, Elio; Gatti, Rosalba; Parenti, Anna; Piazza, Mario

    1984-01-01

    Idiopathic mitral valve prolapse (IMVP) is a very common cardiac abnormality that may be linked to carnitine deficit (inadequate nutritional intake or absorption). One patient with IMVP and related symptoms that were resistant to drug therapy was fully studied. Free plasma carnitine and 24-hour free urine carnitine were measured twice, 10 days apart, after an overnight fast. Findings: Free plasma carnitine 23 and 28 μM/L (our laboratory N=38±2 μM/L); free urine C 25 and 44 μM/24 hr (N=255±66 μM/24 hr); FFA 0.88 mEq/L, Duncombe method (N=0.09-0.60); LDL 42% (N = 44-65); cholesterol 161 mg/dl (N = 180-280); triglycerides 84 mg/dl (N = 50-172); SGOT 79 MU/ml (N = up to 40); SGPT 147 MU/ml (N = up to 40); OCT 11.2 MU/ml (N = up to 10.0); aldolase 11.5 MU/ml (N = up to 3.1, Bruns method). Deltoid biopsy: light microscopy showed the presence of optically empty vacuoles; electron microscopy showed lipid droplets near the subsarcolemma area and intermyofibrillar spaces. The mitochondria contained electron dense granules. The electromyogram was also abnormal. In a random sample of four patients with IMVP and related classic symptoms, we have found low levels of plasma and/or urinary carnitine in each case. This study may be the first step towards L-carnitine therapy for what has previously appeared to be idiopathic cardiomyopathy. Images PMID:15226877

  16. Evidence that L-carnitine and selenium supplementation reduces oxidative stress in phenylketonuric patients.

    Science.gov (United States)

    Sitta, A; Vanzin, C S; Biancini, G B; Manfredini, V; de Oliveira, A B; Wayhs, C A Y; Ribas, G O S; Giugliani, L; Schwartz, I V D; Bohrer, D; Garcia, S C; Wajner, M; Vargas, C R

    2011-04-01

    It is well established that the involvement of reactive species in the pathophysiology of several neurological diseases, including phenylketonuria (PKU), a metabolic genetic disorder biochemically characterized by elevated levels of phenylalanine (Phe). In previous studies, we verified that PKU patients (treated with a protein-restricted diet supplemented with a special formula not containing L-carnitine and selenium) presented high lipid and protein oxidative damage as well as a reduction of antioxidants when compared to the healthy individuals. Our goal in the present study was to evaluate the effect of Phe-restricted diet supplemented with L-carnitine and selenium, two well-known antioxidant compounds, on oxidative damage in PKU patients. We investigated various oxidative stress parameters in blood of 18 treated PKU patients before and after 6 months of supplementation with a special formula containing L-carnitine and selenium. It was verified that treatment with L-carnitine and selenium was capable of reverting the lipid peroxidation, measured by thiobarbituric acid-reactive species, and the protein oxidative damage, measured by sulfhydryl oxidation, to the levels of controls. Additionally, the reduced activity of glutathione peroxidase was normalized by the antioxidant supplementation. It was also verified a significant inverse correlation between lipid peroxidation and L-carnitine blood levels as well as a significant positive correlation between glutathione peroxidase activity and blood selenium concentration. In conclusion, our results suggest that supplementation of L-carnitine and selenium is important for PKU patients since it could help to correct the oxidative stress process which possibly contributes, at least in part, to the neurological symptoms found in phenylketonuric patients.

  17. Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

    Directory of Open Access Journals (Sweden)

    A.C. Gimenes

    2015-04-01

    Full Text Available Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM, but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years with chronic progressive external ophthalmoplegia (CPEO were first compared to 10 healthy controls (mean age±SD=29±7.8 years before they were randomly assigned to receive L-carnitine supplementation (3 g/daily or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal, constant work rate (CWR exercise test, to the limit of tolerance [Tlim] were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min and oxygen consumption (V˙O2 at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min and at Tlim (1223±114 vs 1060±108 mL/min. These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

  18. Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy.

    Science.gov (United States)

    Gimenes, A C; Bravo, D M; Nápolis, L M; Mello, M T; Oliveira, A S B; Neder, J A; Nery, L E

    2015-04-01

    Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

  19. The role of oral L-Carnitine therapy in chronic hemodialysis patients

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    Sabry Alaa

    2010-01-01

    Full Text Available To evaluate the effects of L-carnitine oral supplementation on anemia and cardiac function in patients on maintenance hemodialysis (HD, we studied 55 adult chronic HD patients at our center during the period from January 2006 to June 2006 and divided them into two groups; a group of 20 patients who received 1,500 mg/day oral L-carnitine and a control group of 35 patients. Both groups were on erythropoietin therapy. Echogardiographic studies were performed before and at the end of the study. The mean hemoglobin levels were comparable in the L--carnitine group and the control group at the start and after 6 months of therapy (8.63 ± 1.77 and 9.39 ± 2.02 gm/dL, P= 0.18; 10.49 ± 1.65 and 10.92 ± 2.48 gm/dL, P= 0.76, respectively. The mean weekly maintenance dose of erythropoietin was not statistically significantly different in L-carnitine group (80.16 ± 35.61 units/kg and the control group (91.9 ± 38.21 units/kg, P= 0.20. In addition no significant improvement could be observed in the echogardiographic findings in the L-carnitine group after therapy. We conclude that our study revealed no significant improvement in hemoglobin, erythropoietin dose and echocardiographic findings after six months of therapy. Long-term studies including larger number of patients are required to clarify the questionable role of L-carnitine in the HD patients.

  20. Maternal L-Carnitine Supplementation Improves Brain Health in Offspring from Cigarette Smoke Exposed Mothers.

    Science.gov (United States)

    Chan, Yik Lung; Saad, Sonia; Al-Odat, Ibrahim; Oliver, Brian G; Pollock, Carol; Jones, Nicole M; Chen, Hui

    2017-01-01

    Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the brain is unknown. Here, we investigated the effects of maternal L-Carnitine supplementation on brain markers of oxidative stress, autophagy, mitophagy and mitochondrial energy producing oxidative phosphorylation (OXPHOS) complexes in SE offspring. Female Balb/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation and lactation with or without L-Carnitine supplementation (1.5 mM in drinking water). In 1 day old male SE offspring, brain mitochondrial damage was suggested by increased mitochondrial fusion and reduced autophagosome markers; whereas at 13 weeks, enhanced brain cell damage was suggested by reduced fission and autophagosome markers, as well as increased apoptosis and DNA fragmentation markers, which were partially reversed by maternal L-Carnitine supplementation. In female SE offspring, enhanced mitochondrial regeneration was suggested by decreased fission and increased fusion markers at day 1. At 13 weeks, there was an increase in brain energy demand, oxidative stress and mitochondrial turnover, reflected by the protein changes of OXPHOS complex, fission and autophagosome markers, as well as the endogenous antioxidant, which were also partially normalized by maternal L-Carnitine supplementation. However, markers of apoptosis and DNA fragmentation were not significantly changed. Thus L-Carnitine supplementation may benefit the brain health of the offspring from smoking mothers.

  1. Plasma free and total carnitine measured in children by tandem mass spectrometry.

    Science.gov (United States)

    Osorio, J H; Pourfarzam, M

    2002-11-01

    Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 +/- 2.4 and 23.5 +/- 2.9; one to twelve months: 28.8 +/- 10.2 and 35.9 +/- 11.4; one to seven years: 30.7 +/- 10.3 and 38.1 +/- 11.9; seven to 14 years: 33.7 +/- 11.6, and 43.1 +/- 13.8 micro M, respectively). No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation.

  2. Plasma free and total carnitine measured in children by tandem mass spectrometry

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    J.H. Osorio

    2002-11-01

    Full Text Available Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 ± 2.4 and 23.5 ± 2.9; one to twelve months: 28.8 ± 10.2 and 35.9 ± 11.4; one to seven years: 30.7 ± 10.3 and 38.1 ± 11.9; seven to 14 years: 33.7 ± 11.6, and 43.1 ± 13.8 µM, respectively. No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation.

  3. L-carnitine Mediated Reduction in Oxidative Stress and Alteration in Transcript Level of Antioxidant Enzymes in Sheep Embryos Produced In Vitro.

    Science.gov (United States)

    Mishra, A; Reddy, I J; Gupta, P S P; Mondal, S

    2016-04-01

    The objective of this study was to find out the effect of L-carnitine on oocyte maturation and subsequent embryo development, with L-carnitine-mediated alteration if any in transcript level of antioxidant enzymes (GPx, Cu/Zn-SOD (SOD1) and Mn-SOD (SOD2) in oocytes and developing sheep embryos produced in vitro. Different concentrations of L-carnitine (0 mm, 2.5 mm, 5 mm, 7.5 mm and 10 mm) were used in maturation medium. Oocytes matured with 10 mm L-carnitine showed significantly (p carnitine were not significantly different. Maturation rate was not influenced by supplementation of any experimental concentration of L-carnitine. There was a significant (p carnitine-treated oocytes and embryos than control group. Antioxidant effect of L-carnitine was proved by culturing oocytes and embryos with H2O2 in the presence of L-carnitine which could be able to protect oocytes and embryos from H2O2-induced oxidative damage. L-carnitine supplementation significantly (p carnitine supplementation during in vitro maturation reduces oxidative stress-induced embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH that in turn improved developmental potential of oocytes and embryos and alters transcript level of antioxidant enzymes.

  4. Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets age-related changes in serum fatty acids and carnitine metabolites.

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    Jean A Hall

    Full Text Available The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT, fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA and carnitine metabolites. Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8, were fed control or one of two treatment foods for 6 months. All foods were complete and balanced and met the nutrient requirements for adult dogs, and had similar concentrations of moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively. The treatment diets both contained added L-carnitine (300 mg/kg and 0.6% (treatment food 1 or 1.5% (treatment food 2 added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat. Composition of serum FA was determined by gas chromatography of FA methyl esters. Metabolomic profiles of serum samples were determined from extracted supernatants that were split and run on GC/MS and LC/MS/MS platforms, for identification and relative quantification of small metabolites. Body composition was determined by dual energy x-ray absorptiometry. Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment. Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years vs. mature adult (≤ 7 years dogs, and supplementation with L-carnitine attenuated the effects of aging. The ratio of PUFA to SFA was significantly greater in mature dogs at baseline (P ≤ 0.05. Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner. Dogs consuming treatment food 2 also had increased serum concentrations of lauric and myristic FA, and decreased concentrations of SFA, MUFA, and arachidonate (all P ≤ 0.05 and their PUFA to SFA ratio increased. In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on

  5. 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)...

  6. Effects of Citric Acid and l-Carnitine on Physical Fatigue

    OpenAIRE

    Sugino, Tomohiro; Aoyagi, Sayaka; Shirai, Tomoko; Kajimoto, Yoshitaka; Kajimoto, Osami

    2007-01-01

    We examined the effects of citric acid and l-carnitine administration on physical fatigue. In a double-blind, placebo-controlled, 3-way crossover study, 18 healthy volunteers were randomized to oral citric acid (2,700 mg/day), l-carnitine (1,000 mg/day), or placebo for 8 days. The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 h on 2 occasions. Before the physical load, salivary chromogranin A, measured as a physiological stress marke...

  7. [L-carnitine levels in critical septic patients receiving parenteral nutrition].

    Science.gov (United States)

    Garnacho Montero, J; Ortiz Leyba, C; Jiménez Jiménez, F; Monterrubio Villar, J; Fernández Vega, M D; García Garmendia, J L

    1998-01-01

    Septicemia causes multiple and often not very well understood metabolic alterations. In this sense it is controversial whether or not carnitine is decreased, which may have several implications. Our objective is to measure the plasma carnitine levels in septicemic patients, and to find out whether this is modified if there is a multi-organ dysfunction syndrome (MODS), or if it is dependent on the lipid source. For this we carried out a prospective study in septicemic patients with MODS. These were given exclusively parenteral nutrition (PN) without any carnitine supplementation. The PN of 16 patients contained long chain triglycerides (LCT's), while that of another 12 contained a 1:1 mixture of long and medium chain triglycerides (LCT's and MCT's). We measured the plasma carnitine level at the baseline, after 5 days and after 10 days, using an enzymatic method that measures the total carnitine level (free and esterified). The normal values lie between 35 and 70 mumol/l. We included 28 septicemic patients whose ages were 53.41 +/- 16.51 years, and whose APACHE II on admission was 17 +/- 4. The carnitine levels were: baseline: 60.4 +/- 23.7; 5th day 57.7 +/- 22.9; 10th day 55.7 +/- 21.2 (p = n.s.). Of these patients, 10 had an MODS of septic origins with their baseline levels being: 65.3 +/- 30.9; 5th day 60.3 +/- 23.2; 10th day 61.5 +/- 15.5; while the levels of the 18 septicemic patients without MODS, the baseline levels were 61.9 +/- 13.8; 5th day 58.6 +/- 19.1; 10th day 56.6 +/- 19.3 (p = n.s.). In the patients who were given LCT's the baseline carnitine level was 60.7 +/- 23.1, 5th day 60.1 +/- 23.8; 10th day 58.6 +/- 12.8; while those patients who were given LCT/MCT showed baseline levels of 64.3 +/- 19.5; 5th day 58.6 +/- 19.1; 10th day 57.8 +/- 10.7 (p = n.s.). In our septicemic patients the serum carnitine levels we found were within the normal range, and these remained unchanged during the ten days in those patients with MODS or with the lipid mixture used.

  8. Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets.

    Science.gov (United States)

    Keller, J; Ringseis, R; Koc, A; Lukas, I; Kluge, H; Eder, K

    2012-01-01

    Supplementation of carnitine has been shown to improve performance characteristics such as protein accretion in growing pigs. The molecular mechanisms underlying this phenomenon are largely unknown. Based on recent results from DNA microchip analysis, we hypothesized that carnitine supplementation leads to a downregulation of genes of the ubiquitin proteasome system (UPS). The UPS is the most important system for protein breakdown in tissues, which in turn could be an explanation for increased protein accretion. To test this hypothesis, we fed sixteen male, four-week-old piglets either a control diet or the same diet supplemented with carnitine and determined the expression of several genes involved in the UPS in the liver and skeletal muscle. To further determine whether the effects of carnitine on the expression of genes of the UPS are mediated directly or indirectly, we also investigated the effect of carnitine on the expression of genes of the UPS in cultured C2C12 myotubes and HepG2 liver cells. In the liver of piglets fed the carnitine-supplemented diet, the relative mRNA levels of atrogin-1, E214k and Psma1 were lower than in those of the control piglets (P carnitine-supplemented diet than that in control piglets (P carnitine had no effect on basal and/or hydrocortisone-stimulated mRNA levels of genes of the UPS. In conclusion, this study shows that dietary carnitine decreases the transcript levels of several genes involved in the UPS in skeletal muscle and liver of piglets, whereas carnitine has no effect on the transcript levels of these genes in cultivated HepG2 liver cells and C2C12 myotubes. These data suggest that the inhibitory effect of carnitine on the expression of genes of the UPS is mediated indirectly, probably via modulating the release of inhibitors of the UPS such as IGF-1. The inhibitory effect of carnitine on the expression of genes of the UPS might explain, at least partially, the increased protein accretion in piglets supplemented with

  9. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management

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    Magoulas Pilar L

    2012-09-01

    Full Text Available Abstract Systemic primary carnitine deficiency (CDSP is an autosomal recessive disorder of carnitine transportation. The clinical manifestations of CDSP can vary widely with respect to age of onset, organ involvement, and severity of symptoms, but are typically characterized by episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal myopathy, elevated creatine kinase (CK, and cardiomyopathy in childhood; or cardiomyopathy, arrhythmias, or fatigability in adulthood. The diagnosis can be suspected on newborn screening, but is established by demonstration of low plasma free carnitine concentration (SLC22A5 gene. The incidence of CDSP varies depending on ethnicity; however the frequency in the United States is estimated to be approximately 1 in 50,000 individuals based on newborn screening data. CDSP is caused by recessive mutations in the SLC22A5 gene. This gene encodes organic cation transporter type 2 (OCTN2 which transport carnitine across cell membranes. Over 100 mutations have been reported in this gene with the c.136C > T (p.P46S mutation being the most frequent mutation identified. CDSP should be differentiated from secondary causes of carnitine deficiency such as various organic acidemias and fatty acid oxidation defects. CDSP is an autosomal recessive condition; therefore the recurrence risk in each pregnancy is 25%. Carrier screening for at-risk individuals and family members should be obtained by performing targeted mutation analysis of the SLC22A5 gene since plasma carnitine analysis is not a sufficient methodology for determining carrier status. Antenatal diagnosis for pregnancies at increased risk of CDSP is possible by molecular genetic testing of extracted DNA from chorionic villus sampling or amniocentesis if both mutations in SLC22A5 gene are known. Once the diagnosis of CDSP is established in an individual, an echocardiogram, electrocardiogram, CK concentration

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

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    Sofia Mikkelsen Berg

    2017-03-01

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

  11. L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic-Induced Shrinkage through Interacting with TRPV1 Channels

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    Noushafarin Khajavi

    2014-08-01

    Full Text Available Background/Aims: Ocular surface health depends on conjunctival epithelial (HCjE layer integrity since it protects against pathogenic infiltration and contributes to tissue hydration maintenance. As the same increases in tear film hyperosmolarity described in dry eye disease can increase corneal epithelial transient receptor potential vanilloid type-1 (TRPV1 channel activity, we evaluated its involvement in mediating an osmoprotective effect by L-carnitine against such stress. Methods: Using siRNA gene silencing, Ca2+ imaging, planar patch-clamping and relative cell volume measurements, we determined if the protective effects of this osmolyte stem from its interaction with TRPV1. Results: TRPV1 activation by capsaicin (CAP and an increase in osmolarity to ≈ 450 mOsM both induced increases in Ca2+ levels. In contrast, blocking TRPV1 activation with capsazepine (CPZ fully reversed this response. Similarly, L-carnitine (1 mM also reduced underlying whole-cell currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume shrinkage was fully blocked during exposure to L-carnitine. On the other hand, in TRPV1 gene-silenced cells, this protective effect by L-carnitine was obviated. Conclusion: The described L-carnitine osmoprotective effect is elicited through suppression of hypertonic-induced TRPV1 activation leading to increases in L-carnitine uptake through a described Na+-dependent L-carnitine transporter.

  12. Pharmacological evaluation of a β-hydroxyphosphonate analogue of l-carnitine in obese Zucker fa/fa rats.

    Science.gov (United States)

    Reyes-Esparza, Jorge; Mendoza-Rivera, Brissa; De la Cruz-Cordero, Ricardo; Rosado, Jorge L; Duarte-Vázquez, Miguel Á; Solis, Mario G; Vite-Vallejo, Odón; Rodríguez-Fragoso, Lourdes

    2013-04-01

    In this study, we evaluated the effect of an analogue of l-carnitine on parameters involved with Metabolic Syndrome in obese Zucker rats. Twenty-four rats were treated for 5 weeks with l-carnitine (300 mg/kg) and its analogue at two concentrations (100 and 250 mg/kg) to assess their impact on glucose, triglycerides and cholesterol in liver and blood samples, as well as the amount of liver glycogen. Liver slices were also analysed. The analogue reduced the levels of glucose, triglycerides and cholesterol in liver and the level of triglycerides in serum. At 100 mg/kg, the analogue proved more effective than l-carnitine in improving the biochemical alterations present in liver. The amount of liver glycogen content was higher in obese animals treated with both l-carnitine and the analogue. No changes on insulin and leptin were observed in animals treated. l-carnitine and its analogue reduced the microvesicular fatty infiltration in liver. This study demonstrated that the analogue tested is more potent and efficient than l-carnitine and improves the pharmacological profile of l-carnitine.

  13. The effect of marathon running on carnitine metabolism and on some aspects of muscle mitochondrial activities and antioxidant mechanisms.

    Science.gov (United States)

    Cooper, M B; Jones, D A; Edwards, R H; Corbucci, G C; Montanari, G; Trevisani, C

    1986-01-01

    Carnitine is an essential co-factor in the catabolism of fats as an energy source. The primary purpose of this study was to investigate the effect of running a marathon on the metabolism of carnitine by endurance-trained athletes, and to evaluate the effect of carnitine administration on the performance of such exercise. The effects of marathon running on mitochondrial enzymes and cellular anti-oxidants were also examined to assess whether the expression of these activities is altered by exercise. Subjects were 10 experienced male marathon runners aged between 19 and 25 years. Running a marathon caused a fall in the plasma content of unesterified carnitine (37%) and an increase in the level of acetylcarnitine present (288%). Loading of the athletes with L-carnitine for 10 days before running a marathon abolished the exercise-induced fall in plasma-free carnitine (P less than 0.05) whilst amplifying the production of acetylcarnitine (P less than 0.05). Carnitine loading of the athletes studied made no detectable improvement in performance of the marathon (P greater than 0.05). Cytochrome oxidase, succinate cytochrome C reductase and superoxide dismutase activities present in skeletal muscle were unaltered by marathon running. However, such exercise caused a large increase in the tissue content of oxidized glutathione (189%) at the expense of reduced glutathione (-18%).

  14. The effect of L-Carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients

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    M M Suchitra

    2011-01-01

    Full Text Available Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L-Carnitine supplementation may have potential benefits in improving dialysis-related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP, total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P < 0.05. However, no significant change was observed in the lipid parameters and nutritional markers in the Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group.

  15. L-Carnitine Supplementation Reduces Short-Term Neutrophil-Lymphocyte Ratio in Patients Undergoing Coronary Artery Bypass Grafting.

    Science.gov (United States)

    Aldemir, Mustafa; Pektaş, Mehmet Bilgehan; Parlar, Ali İhsan; Akcı, Önder; Emren, Sadık Volkan; Tecer, Evren; Adalı, Fahri; Yüksel, Şeref; Darçın, Osman Tansel

    2015-07-01

    This study aims to investigate whether preoperative L-carnitine supplementation affects the neutrophil-to-lymphocyte ratio (NLR) in patients undergoing coronary artery bypass grafting surgery. The neutrophil-to-lymphocyte ratio is an inflammatory marker that has proven usefulness for predicting postoperative complications in coronary artery bypass surgery. A lot of studies concerning the role of L-carnitine in the immune system have been performed, contradictory results have been reported on its effects on absolute numbers of WBC subtypes. This randomized, double-blinded, placebo-controlled study was conducted among patients scheduled for coronary artery bypass grafting surgery between June 2012 and December 2013 in our cardiovascular surgery clinic. A total of 60 consecutive patients were randomized and divided into 2 groups. The first group received 2 g of L-carnitine in 1000 mL of 0.9% saline solution infused over 24 hours for each of the 3 preoperative days (L-carnitine group, n = 30), or only 1000 mL of 0.9% saline solution for the same time period (placebo group, n = 30). The basal values of leukocyte, neutrophil, lymphocyte counts, and neutrophil to lymphocyte ratio were similar in the 2 groups. After L-carnitine supplementation (just before surgery), leukocyte and neutrophil counts of the L-carnitine group were significantly lower than those of the placebo group (7.7 ± 1.5 versus 9.7 ± 2.6, P carnitine group (1.1 ± 0.6 versus 0.8 ± 0.9, P carnitine group at postoperative day 1 (20.7 ± 13.8 versus 10.8 ± 4.1, P carnitine supplementation may reduce neutrophil-lymphocyte ratio during the early postoperative period of coronary artery bypass grafting surgery.

  16. Neuroprotective Effects of Pre-Treament with l-Carnitine and Acetyl-l-Carnitine on Ischemic Injury In Vivo and In Vitro

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    Shunjiang Xu

    2012-02-01

    Full Text Available The therapeutic effect of stroke is hampered by the lack of neuroprotective drugs against ischemic insults beyond the acute phase. Carnitine plays important roles in mitochondrial metabolism and in modulating the ratio of coenzyme A (CoA/acyl-CoA. Here, we investigate the neuroprotective effects of l-carnitine (LC and Acetyl-l-carnitine (ALC pre-treatment on ischemic insults under the same experimental conditions. We used a transient middle cerebral artery occlusion (MCAO model to evaluate the protective roles of LC and ALC in acute focal cerebral ischemia in vivo and to understand the possible mechanisms using model of PC12 cell cultures in vitro. Results showed that ALC, but not LC, decreased infarction size in SD rats after MCAO in vivo. However, both LC and ALC pretreatment reduced oxygen-glucose deprivation (OGD-induced cell injury and decreased OGD-induced cell apoptosis and death in vitro; at the same time, both of them increased the activities of super oxide dismutase (SOD and ATPase, and decreased the concentration of malondialdehyde (MDA in vitro. Thus, our findings suggested that LC and ALC pre-treatment are highly effective in the prevention of neuronal cell against ischemic injury in vitro, however, only ALC has the protective effect on neuronal cell injury after ischemia in vivo.

  17. Supplementation of maturation medium with L-carnitine improves cryo-tolerance of bovine in vitro matured oocytes.

    Science.gov (United States)

    Chankitisakul, Vibuntita; Somfai, Tamas; Inaba, Yasushi; Techakumphu, Mongkol; Nagai, Takashi

    2013-03-01

    The objective was to determine the effects of adding L-carnitine (an enhancer of lipid metabolism) during IVM, on cryotolerance and developmental competence of bovine oocytes. Oocytes matured in the absence (control) or presence (0.6 mg/mL) of L-carnitine were subjected to IVF and embryo culture after Cryotop vitrification or nonvitrification at the metaphase stage of the second meiotic cell division. Cleavage and blastocyst formation rates, and inner cell mass and trophectoderm cell numbers were determined. Also, ATP content in IVM oocytes was measured and intracellular lipid droplets were observed (Nile red staining and confocal microscopy). L-carnitine had no significant effect on the rate of matured oocytes. Vitrification reduced (P carnitine groups (82.7 ± 5.1%) compared with nonvitrified oocytes (100%). After IVF, cleavage rates of vitrified control and L-carnitine groups (56.5 ± 3.9% and 62.8 ± 5.1%, respectively) were significantly lower than those in nonvitrified control and L-carnitine groups (83.9 ± 4.2% and 84.3 ± 1.3%). After vitrification, blastocyst formation rate in the L-carnitine group (54.4 ± 5.2%) was significantly higher compared with the control (34.9 ± 4.4%), and did not significantly differ from those in nonvitrified control and L-carnitine groups (52.1 ± 4.2% and 52.8 ± 3.0%). The numbers and ratio of inner cell mass and trophectoderm cells in blastocysts did not differ significantly among groups. The ATP content in L-carnitine-treated oocytes tended to be higher compared with the control. Vitrification did not reduce ATP content in oocytes, irrespective of L-carnitine treatment. Treatment with L-carnitine dislocated lipid droplets from the peripheral area to the inner cytoplasm. In conclusion, L-carnitine supplementation during IVM redistributed lipid droplets in oocytes; if they survived vitrification, their developmental competence was similar to that of nonvitrified oocytes.

  18. L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death

    Science.gov (United States)

    Le Borgne, Françoise; Ravaut, Gaétan; Bernard, Arnaud; Demarquoy, Jean

    2017-01-01

    AIM To identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells. METHODS Myoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine (a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death. RESULTS Associated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species (ROS), especially under pathological conditions. High levels of ROS are known to induce injuries in cell structure as they interact at many levels in cell function. In C2C12 cells, a treatment with menadione induced a loss of transmembrane mitochondrial potential, an increase in mitochondrial production of ROS; it also induces autophagy and was able to provoke cell death. Pre-treatment of the cells with L-carnitine reduced ROS production, diminished autophagy and protected C2C12 cells against menadione-induced deleterious effects. CONCLUSION In conclusion, L-carnitine limits the oxidative stress in these cells and prevents cell death.

  19. Effects of Citric Acid and l-Carnitine on Physical Fatigue.

    Science.gov (United States)

    Sugino, Tomohiro; Aoyagi, Sayaka; Shirai, Tomoko; Kajimoto, Yoshitaka; Kajimoto, Osami

    2007-11-01

    We examined the effects of citric acid and l-carnitine administration on physical fatigue. In a double-blind, placebo-controlled, 3-way crossover study, 18 healthy volunteers were randomized to oral citric acid (2,700 mg/day), l-carnitine (1,000 mg/day), or placebo for 8 days. The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 h on 2 occasions. Before the physical load, salivary chromogranin A, measured as a physiological stress marker, was lower in the group given citric acid than in the group given placebo. Also, after the physical load, the subjective feeling of fatigue assessed with a visual analogue scale was lower in the citric acid group than in the placebo group. In contrast, l-carnitine had no effect on chromogranin A or subjective fatigue. These results suggest that citric acid reduces physiological stress and attenuates physical fatigue, whereas l-carnitine does not.

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

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    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.

  1. 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

  2. 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

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

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    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.

  4. Different surgical techniques and L-carnitine supplementation in an experimental varicocele model.

    Science.gov (United States)

    Akdemir, S; Gurocak, S; Konac, E; Ure, I; Onen, H I; Gonul, I I; Sozen, S; Menevse, A

    2014-10-01

    We aimed to investigate the impact of various varicocelectomy techniques and/or L-carnitine as an adjunct treatment, following the emergence of oxidative stress, on the expression levels of SCF/c-kit signalling pathways in spermatogenesis. Forty-two rats were divided into seven groups: group 1 (G1) control; group 2 (G2) sham; group 3 (G3) varicocele; group 4 (G4) varicocele + varicocelectomy with testicular nonartery sparing; group 5 (G5) same as G4 but with artery sparing; group 6 (G6) same as G4 but with L-carnitine and group 7 (G7) same as G5 with L-carnitine. mRNA expression levels of SCF and c-kit were measured quantitatively using real-time polymerase chain reaction. CASP-3 activity at protein level was determined, and histological evaluation was performed. mRNA expression level of SCF increased in G6 as compared to control group (3.52-folds change; P = 0.035), whereas mRNA expression level of c-kit gene remained the same. We found that in the left testis of G6 group, mRNA expression level of SCF increased 2.2-folds in comparison with the right testis (P carnitine may be considered as supportive treatment regimes in addition to conventional surgical treatments.

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

    Science.gov (United States)

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

    2012-07-01

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

  6. 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.

  7. Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Ferrari, Ilaria; D'Angelo, Angela; Fogari, Elena; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

    2010-01-01

    Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.

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

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    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.

  9. Doxorubicin Toxicity can be Ameliorated during Antioxidant L-Carnitine Supplementation

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    Othman A. Alshabanah

    2010-01-01

    Full Text Available Doxorubicin is an antibiotic broadly used in treatment of different types of solid tumors. The present study investigates whether L-carnitine, antioxidant agent, can reduce the hepatic damage induced by doxorubicin. Male Wistar albino rats were divided into six groups: group 1 was intraperitoneal injected with normal saline for 10 consecutive days; group 2, 3 and 4 were injected every other day with doxorubicin (3 mg/kg, i.p., to obtain treatments with cumulative doses of 6, 12 and 18 mg/kg. The fifth group was injected with L-carnitine (200 mg/kg, i.p. for 10 consecutive days and the sixth group was received doxorubicin (18 mg/kg and L-carnitine (200 mg/kg. High cumulative dose of doxorubicin (18 mg/kg significantly increases the biochemical levels of alanine transaminase, alkaline phosphatase, total bilirubin, thiobarbituric acid reactive substances (TBARs, total nitrate/nitrite (NOx p < 0.05 and decrease in glutathione (GSH , superoxide dismutase (SOD, glutathione peroxidase (GSHP x, glutathione-s-transferase (GST, glutathione reductase (GR and catalase (CAT activity p < 0.05. The effect of doxorubicin on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control p < 0.05. Interestingly, L-carnitine supplementation completely reversed the biochemical and gene expression levels induced by doxorubicin to the control values. In conclusion, data from this study suggest that the reduction of antioxidant defense during doxorubicin administration resulted in hepatic injury could be prevented by L-carnitine supplementation by decreasing the oxidative stress and preserving both the activity and gene expression level of antioxidant enzymes.

  10. Radiolysis of D(+)-carnitine by /sup 60/Co-. gamma. -radiation and formation of L(+)-. beta. -methylcholine

    Energy Technology Data Exchange (ETDEWEB)

    Loester, Heinz; Strack, Erich; Seim, Hermann

    1986-06-01

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

  11. Influence of acetyl-L-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients.

    Science.gov (United States)

    Gasparetto, A; Corbucci, G G; De Blasi, R A; Antonelli, M; Bagiella, E; D'Iddio, S; Trevisani, C

    1991-01-01

    The clinical use of acetyl carnitine in circulatory shock has its theoretical basis in the ability of this molecule to restore enzyme activity inhibited by hypoxia, acting as an acetyl donor. Moreover the action of carnitine on an injured myocardium encouraged us to examine the clinical effect of this drug during heart failure. A double-blind clinical study was performed in ten Italian intensive care units on 115 patients with septic, cardiac of traumatic shock, by using acetyl-L-carnitine infusion for 12 hours, with a previous single bolus intravenously. The results showed a good response to the drug in terms of blood oxygenation during the course of sepsis and heart failure. The heart rate as well as right atrial pressure decreased significantly in patients with cardiogenic shock. In septic patients systolic and mean arterial pressures increased also. The present data suggests the use of acetyl-L-carnitine as an adjuvant to the commonly used therapy in hypoxic conditions.

  12. Levels of carnitine and acylcarnitines in reconstituted red blood cell samples washed with different concentrations of saline solutions

    Directory of Open Access Journals (Sweden)

    José Henry Osorio

    2011-01-01

    Full Text Available Objective: To evaluate the percentage of carnitine and acylcarnitines remaining in red blood cells after washing them with different concentrations of saline solution. Materials and methods: Human blood samples were centrifuged and the blood cells were washed with different saline solutions. The final pellet was resuspended in PBS for card preparation and tandem mass spectrometry analysis. Results: It was found that carnitine, as well as short-chain, medium-chain, and long-chain acylcarnitines remain in red blood cells at average percentages of 19.3; 34; 34; and 32%, respectively. Significant differences were found for carnitine and acylcarnitine levels in blood washed with an isotonic solution compared to their levels using several hypotonic solutions (p<0.05. Conclusion: Because carnitine and acylcarnitines remained associated with the blood cells, we recommend using whole blood to measure these metabolites.

  13. Levels of carnitine and acylcarnitines in reconstituted red blood cell samples washed with different concentrations of saline solutions

    Directory of Open Access Journals (Sweden)

    José Henry Osorio

    2010-12-01

    Full Text Available Objective: To evaluate the percentage of carnitine and acylcarnitines remaining in red blood cells after washing them with different concentrations of saline solution.Materials and methods: Human blood samples were centrifuged and the blood cells were washed with different saline solutions. The final pellet was resuspended in PBS for card preparation and tandem mass spectrometry analysis.Results: It was found that carnitine, as well as short-chain, medium-chain, and long-chain acylcarnitines remain in red blood cells at average percentages of 19.3; 34; 34; and 32%, respectively. Significant differences were found for carnitine and acylcarnitine levels in blood washed with an isotonic solution compared to their levels using several hypotonic solutions (p<0.05.Conclusion: Because carnitine and acylcarnitines remained associated with the blood cells, we recommend using whole blood to measure these metabolites.

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

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    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.

  15. 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 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 fibres (P = 0.11), and increased specific lactate dehydrogenase activity (P = 0.09) in ST indicating a more

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

    OpenAIRE

    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...

  17. 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.

  18. The Effects of Oral L-Carnitine Supplementation on Physical Capacity and Lipid Metabolism in Chronic Hemodialysis Patients

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    Yasuo Kudoh

    2014-03-01

    Full Text Available Background: It is well known that the physical activity in chronic hemodialysis patients decreases compared to that in normal subjects. In order to investigate the effects of L-carnitine on physical capacity and lipid metabolism, a cardiopulmonary exercise test using a bicycle ergometer was performed before and after 3 months of oral L-carnitine supplementation under double-blind conditions. Methods and Results: A total of 20 stable outpatients undergoing hemodialysis treatment were randomly divided into 2 groups: controls receiving placebo and patients receiving 900 mg L-carnitine p.o. daily. The levels of free and acyl carnitine increased significantly from 22.9 ± 7.3 to 149.9 ± 51.8 μmol/l and from 16.0 ± 2.8 to 100.3 ± 50.2 μmol/l, respectively, in the L-carnitine group; however, there was no significant change in other plasma lipid profiles. The exercise time was decreased and the heart rate at the anaerobic threshold was increased in the control group 3 months after the study period, but there were no such changes observed in the L-carnitine group. The minute ventilation/CO2 output slope increased significantly from 38.9 ± 7.8 to 43.8 ± 11.8 in the L-carnitine group. It has been speculated that a shift in the energy source occurs from carbohydrate to lipid, in terms of an increase of oxygen demand. Conclusion:L-Carnitine supplementation might have some beneficial effects on the physical capacity of chronic hemodialysis patients due to the improvement of the lipid metabolism in the muscle.

  19. Levels of carnitine and acylcarnitines in reconstituted red blood cell samples washed with different concentrations of saline solutions

    OpenAIRE

    José Henry Osorio; Morteza Pourfarzam

    2011-01-01

    Objective: To evaluate the percentage of carnitine and acylcarnitines remaining in red blood cells after washing them with different concentrations of saline solution. Materials and methods: Human blood samples were centrifuged and the blood cells were washed with different saline solutions. The final pellet was resuspended in PBS for card preparation and tandem mass spectrometry analysis. Results: It was found that carnitine, as well as short-chain, medium-chain, and long-chain acylca...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-08-01

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

  1. Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress.

    Science.gov (United States)

    Shaker, M E; Houssen, M E; Abo-Hashem, E M; Ibrahim, T M

    2009-09-01

    This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl(4) and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride (CCl(4)) (1 ml/kg/3 days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day, i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter, changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH) content, hepatic superoxide dismutase (SOD) activity, and serum total antioxidant capacity (TAC) level were evaluated. In CCl(4)-induced liver fibrosis, the efficacy order was melatonin > L-carnitine > vitamin E, while in STZ-induced diabetes, the efficacy order was vitamin E > or = melatonin > L-carnitine. In conclusion, these data indicate that low dose of melatonin is more effective than high doses of vitamin E and L-carnitine in reducing hepatic oxidative stress induced by CCl(4) and diabetes. Moreover, the potent effect of vitamin E in ameliorating diabetes can be linked not only to the antioxidant actions, but also to the superior effect in reducing diabetes-induced hyperglycaemia. Meanwhile, potency of L-carnitine was nearly the same in CCl(4) and diabetes-induced liver damage.

  2. L-Carnitine changes the levels of insulin-like growth factors (IGFs) and IGF binding proteins in streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Heo, Y R; Kang, C W; Cha, Y S

    2001-10-01

    This study investigated the effects of L-carnitine on insulin-like growth factor-I/II (IGF-I/II) and insulin-like growth factor binding proteins (IGFBPs) in streptozotocin (STZ)-induced diabetic rats. Each rat in the three L-carnitine-treated groups was injected subcutaneously with L-carnitine, 50 (D50), 100 (D100), or 200 (D200) mg/kg body weight every other day for four weeks, and animals in normal (N) and diabetic (DM) groups received saline by the same method. Diabetic rats had significantly lower carnitine concentrations in serum and liver compared with normal rats. Total carnitine concentrations were increased dose-dependently by carnitine treatment. Total IGF-I in serum from diabetic rats was increased dose-dependently by carnitine treatment, but was statistically significant only in the D200 group. The expression of liver IGF-I mRNA was lower in diabetic rats than in normal rats and increased by L-carnitine treatment. L-Carnitine treatment of diabetic rats had no effect on the levels of IGF-II in serum, liver, and kidney. Although the levels of IGF-II in serum and kidney of diabetic rats were increased in comparison with normal rats, IGF-II mRNA was not expressed in liver. Diabetic rats had markedly lower IGFBP-3 than normal rats did, and IGFBP-3 was increased by L-carnitine treatment. These results demonstrate that L-carnitine treatment of diabetic rats modulates the IGFs/IGFBPs axis. Especially note-worthy is that L-carnitine at a dose of 200 mg/kg/48 h for four weeks was able to restore serum total IGF-I in STZ-induced diabetic rats to nearly normal levels.

  3. 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...

  4. Dietary L-carnitine supplementation increases lipid deposition in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco) through changes in lipid metabolism.

    Science.gov (United States)

    Zheng, Jia-Lang; Luo, Zhi; Zhuo, Mei-Qing; Pan, Ya-Xiong; Song, Yu-Feng; Hu, Wei; Chen, Qi-Liang

    2014-09-14

    Carnitine has been reported to improve growth performance and reduce body lipid content in fish. Thus, we hypothesised that carnitine supplementation can improve growth performance and reduce lipid content in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco), a commonly cultured freshwater fish in inland China, and tested this hypothesis in the present study. Diets containing l-carnitine at three different concentrations of 47 mg/kg (control, without extra carnitine addition), 331 mg/kg (low carnitine) and 3495 mg/kg (high carnitine) diet were fed to yellow catfish for 8 weeks. The low-carnitine diet significantly improved weight gain (WG) and reduced the feed conversion ratio (FCR). In contrast, the high-carnitine diet did not affect WG and FCR. Compared with the control diet, the low-carnitine and high-carnitine diets increased lipid and carnitine contents in the liver and muscle. The increased lipid content in the liver could be attributed to the up-regulation of the mRNA levels of SREBP, PPARγ, fatty acid synthase (FAS) and ACCa and the increased activities of lipogenic enzymes (such as FAS, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme) and to the down-regulation of the mRNA levels of the lipolytic gene CPT1A. The increased lipid content in muscle could be attributed to the down-regulation of the mRNA levels of the lipolytic genes CPT1A and ATGL and the increased activity of lipoprotein lipase. In conclusion, in contrast to our hypothesis, dietary carnitine supplementation increased body lipid content in yellow catfish.

  5. Carnitine palmitoyltransferase-1A deficiency: a look at classic and arctic variants.

    Science.gov (United States)

    Dykema, Deanna M

    2012-02-01

    Carnitine palmitoyltransferase-1A (CPT-1A) deficiency is a defect of fatty acid metabolism that presents as an autosomal recessive inheritance. Carnitine palmitoyltransferase-1A is the rate-limiting enzyme that allows the body to process fats to provide energy during times of fasting and illness. Patients usually present between birth and 18 months of age following an illness with various symptoms including hypoketotic hypoglycemia, lethargy, and seizures. Diagnosis can be achieved through newborn metabolic screening. Long-term treatment is managed through dietary management. A milder form has been found to occur at a much higher incidence in the Inuit population. Since the recent discovery of CPT-1A deficiency, much is yet to be learned. Researchers are busy identifying and studying groups of people who are presenting with CPT-1A deficiency at significantly higher rates than the general population. This research will lead to a better understanding and future care of individuals diagnosed with CPT-1A deficiency.

  6. 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.

  7. 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.

  8. 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......, the implication being that they may significantly influence the manifestation of clinical disease and could therefore potentially be considered as a susceptibility variants. Among myopathic individuals, males comprised 88% of patients, suggesting increased susceptibility to clinical disease. A small number...

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

    OpenAIRE

    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...

  10. 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.

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

    OpenAIRE

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

    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 palmit...

  12. Improved N-retention during L-carnitine-supplemented total parenteral nutrition

    OpenAIRE

    Bohles, H.; Segerer, Hugo; Fekl, W.

    1984-01-01

    The influence of intravenously administered L-carnitine on lipid- and nitrogen-metabolism was studied during total parenteral nutrition of piglets (mean weight 4077 g; n = 9). The infusion protocol was divided into three isocaloric and isonitrogenous 48-hr periods. Amino acids (3 g/kg day) were administered throughout all three periods: 140 cal/kg/day were given as nonprotein calories, consisting only of glucose during period 1; during periods 2 and 3, an amount of glucose calorically equival...

  13. The effects of acute L-carnitine supplementation on endurance performance of athletes.

    Science.gov (United States)

    Orer, Gamze E; Guzel, Nevin A

    2014-02-01

    This study examined the effect of acute L-carnitine loading on the endurance performance of footballers. Measurements were performed on 26 candidate professional footballers who volunteered to take part in the study. Athletes were given a glass of fruit juice 1 hour before applying L-carnitine with the double-blind method. Then, 12 participants were given 3 g of L-carnitine (LK-3) and the remaining 14 were given 4 g (LK-4). Athletes began the exercise test at a running speed of 8 km·h and then continued at 10 km·h. The speed was increased 1 km·h every 3 minutes, and the test continued until the subject chose to quit. Heart rate was registered using a portable telemetric heart rate monitor during the test. Blood samples were taken from the earlobes of the footballers both before the test and before the speed increase (during the 1-minute interval), and the lactate (La) concentration was measured electroenzymatically. The test was repeated after 1 week as a group of placebos (P-3 and P-4). The result showed that the running speeds corresponding to specific La concentrations were increased, and La and heart rate responses to the running speeds were decreased in both supplemented groups compared with placebos (p ≤ 0.05). A significant reduction in heart rate was found in LK-4 and P-4 (p ≤ 0.05). When the Borg responses to the running speeds were analyzed, a significant difference was found in both supplemented groups (p ≤ 0.05). The results show that 3 or 4 g of L-carnitine taken before physical exercise prolonged exhaustion.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cederblad, G.; Carlin, J.I.; Constantin-Teodosiu, D.; Harper, P.; Hultman, E. (Karolinska Institute, Huddinge Hospital (Sweden))

    1990-03-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Servillo, Luigi; Giovane, Alfonso; Cautela, Domenico; Castaldo, Domenico; Balestrieri, Maria Luisa

    2014-01-01

    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.

  19. Improved N-retention during L-carnitine-supplemented total parenteral nutrition.

    Science.gov (United States)

    Bohles, H; Segerer, H; Fekl, W

    1984-01-01

    The influence of intravenously administered L-carnitine on lipid- and nitrogen-metabolism was studied during total parenteral nutrition of piglets (mean weight 4077 g; n = 9). The infusion protocol was divided into three isocaloric and isonitrogenous 48-hr periods. Amino acids (3 g/kg day) were administered throughout all three periods: 140 cal/kg/day were given as nonprotein calories, consisting only of glucose during period 1; during periods 2 and 3, an amount of glucose calorically equivalent to 4 g fat/kg/day was substituted with a lipid emulsion, and L-carnitine (1.5 mg/kg/day) was added in period 3. Key parameters of fat- and nitrogen-metabolism were determined during the entire regime. Indirect calorimetry was performed and the respiratory quotient calculated during all three periods. The results demonstrate a more effective lipolysis and oxidation of fatty acids during L-carnitine supplementation. These changes produce an increased energy gain from exogenously administered fat and a distinct improvement in nitrogen balance.

  20. L-carnitine protects against carboplatin-mediated renal injury: AMPK- and PPARα-dependent inactivation of NFAT3.

    Directory of Open Access Journals (Sweden)

    Yuh-Mou Sue

    Full Text Available We have previously shown that carboplatin induces inflammation and apoptosis in renal tubular cells (RTCs through the activation of the nuclear factor of activated T cells-3 (NFAT3 protein by reactive oxygen species (ROS, and that the ROS-mediated activation of NFAT3 is prevented by N-acetyl cysteine and heme oxygenase-1 treatment. In the current study, we investigated the underlying molecular mechanisms of the protective effect of L-carnitine on carboplatin-mediated renal injury. Balb/c mice and RTCs were used as model systems. Carboplatin-induced apoptosis in RTCs was examined using terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling. We evaluated the effects of the overexpression of the peroxisome-proliferator-activated receptor alpha (PPARα protein, the knockdown of PPARα gene, and the blockade of AMPK activation and PPARα to investigate the underlying mechanisms of the protective effect of L-carnitine on carboplatin-mediated renal injury. Carboplatin reduced the nuclear translocation, phosphorylation, and peroxisome proliferator responsive element transactivational activity of PPARα. These carboplatin-mediated effects were prevented by L-carnitine through a mechanism dependent on AMPK phosphorylation and subsequent PPARα activation. The activation of PPARα induced cyclooxygenase 2 (COX-2 and prostacyclin (PGI2 synthase expression that formed a positive feedback loop to further activate PPARα. The coimmunoprecipitation of the nuclear factor (NF κB proteins increased following the induction of PPARα by L-carnitine, which reduced NFκB transactivational activity and cytokine expression. The in vivo study showed that the inactivation of AMPK suppressed the protective effect of L-carnitine in carboplatin-treated mice, indicating that AMPK phosphorylation is required for PPARα activation in the L-carnitine-mediated protection of RTC apoptosis caused by carboplatin. The results of our study provide molecular evidence

  1. Effects of high carnitine supplementation on substrate utilization in low-birth-weight infants receiving total parenteral nutrition.

    Science.gov (United States)

    Sulkers, E J; Lafeber, H N; Degenhart, H J; Przyrembel, H; Schlotzer, E; Sauer, P J

    1990-11-01

    Parenterally fed preterm neonates are known to be at risk for carnitine deficiency. We studied substrate utilization in low-birth-weight infants receiving total parenteral nutrition (TPN) with (A) and without (B) supplementation of 48 mg carnitine.kg-1.d-1 on days 4-7 (birth weights 1334 +/- 282 vs 1318 +/- 248 g, gestational age 32 +/- 2 vs 32 +/- 2 wk, A vs B, respectively). TPN consisted of 11 g glucose.kg-1.d-1 and 2.4 g.kg-1.d-1 of both protein and fat. Plasma carnitine concentrations at day 7 were for free carnitine 11.8 +/- 5.0 vs 164 +/- 56 mumol/L and for acyl carnitine 3.8 +/- 2.0 vs 33.9 +/- 15.4 mumol/L, respectively. Indirect calorimetry at day 7 showed a higher fat oxidation (0.21, -0.31 to +0.60 vs 1.18, 0.70 to 1.95 g. kg-1.d-1, respectively, P less than 0.02, median and interquartile range) in group B and a higher protein oxidation (0.37, 0.30-0.43 vs 0.63, 0.53-0.88 g.kg-1.d-1, P less than 0.001). The time to regain birth weight was also higher in group B (7, 5.5-9 vs 9, 7-14 d, P less than 0.05). Carnitine supplementation and calorie intake were the best explanatory variables for metabolic rate (R2 = 0.45, P less than 0.002). We conclude that carnitine supplementation of TPN in this dosage does not seem advisable.

  2. Oxidative stress parameters in urine from patients with disorders of propionate metabolism: a beneficial effect of L:-carnitine supplementation.

    Science.gov (United States)

    Ribas, Graziela S; Biancini, Giovana B; Mescka, Caroline; Wayhs, Carlos Y; Sitta, Angela; Wajner, Moacir; Vargas, Carmen R

    2012-01-01

    Propionic (PA) and methylmalonic (MMA) acidurias are inherited disorders caused by deficiency of propionyl-CoA carboxylase and methylmalonyl-CoA mutase, respectively. Affected patients present acute metabolic crises in the neonatal period and long-term neurological deficits. Treatments of these diseases include a protein restricted diet and L: -carnitine supplementation. L: -Carnitine is widely used in the therapy of these diseases to prevent secondary L: -carnitine deficiency and promote detoxification, and several recent in vitro and in vivo studies have reported antioxidant and antiperoxidative effects of this compound. In this study, we evaluated the oxidative stress parameters, isoprostane and di-tyrosine levels, and the antioxidant capacity, in urine from patients with PA and MMA at the diagnosis, and during treatment with L: -carnitine and protein-restricted diet. We verified a significant increase of isoprostanes and di-tyrosine, as well as a significant reduction of the antioxidant capacity in urine from these patients at diagnosis, as compared to controls. Furthermore, treated patients presented a marked reduction of isoprostanes and di-tyrosine levels in relation to untreated patients. In addition, patients with higher levels of protein and lipid oxidative damage, determined by di-tyrosine and isoprostanes levels, also presented lower urinary concentrations of total and free L: -carnitine. In conclusion, the present results indicate that treatment with low protein diet and L: -carnitine significantly reduces urinary biomarkers of protein and lipid oxidative damage in patients with disorders of propionate metabolism and that L: -carnitine supplementation may be specially involved in this protection.

  3. L-Carnitine supplementation during suckling intensifies the early postnatal skeletal myofiber formation in piglets of low birth weight.

    Science.gov (United States)

    Lösel, D; Kalbe, C; Rehfeldt, C

    2009-07-01

    Piglets of low birth weight exhibit a reduced total number of skeletal myofibers at birth and throughout life compared with piglets of middle and heavy birth weight, which is associated with impaired (lean) growth and quality of carcass and meat at market weight. We investigated the effect of L-carnitine supplementation to suckling piglets of different birth weights on early postnatal myofiber formation, muscle growth, and body composition. A total of 48 piglets of low (LW) and middle (MDW) birth weight from 9 German Landrace gilts received 400 mg of L-carnitine (carnitine, n = 25) or a placebo (control, n = 23) once daily from d 7 to 27 of age and were slaughtered on d 28 of age (weaning). Carnitine-supplemented piglets deposited less fat as indicated by a reduced proportion of perirenal (P = 0.1) and intramuscular fat (P = 0.05). Circulating glucose concentrations tended to be greater in supplemented LW piglets (P = 0.13). The concentration of carnitine in semitendinosus (STN) muscle was approximately doubled (P supplementation, with emphasis on the proportion of esterified carnitine. The ratio of lactate dehydrogenase to isocitrate dehydrogenase tended (P = 0.12) to be smaller in STN muscle of supplemented piglets, indicating a more oxidative muscle metabolism. The total number of STN myofibers was increased by 13% (P = 0.02) in supplemented LW piglets, thereby reaching the unchanged level of MDW littermates. In addition, supplemented LW piglets displayed a 2.4-fold mRNA expression of the gene encoding the embryonic isoform of the myosin heavy chain in STN muscle than control piglets (P = 0.05), but there were no differences in the proportion of fibers positively staining for the embryonic myosin isoform. L-carnitine-supplemented piglets exhibited a greater DNA:protein ratio (P = 0.02) in STN muscle, which resulted from a greater DNA concentration (P = 0.04). However, the STN muscle of L-carnitine-supplemented piglets was not less mature as indicated by

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

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    Li Jin-Lian

    2012-03-01

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

  5. Effect of L-Carnitine Supplementation on Reverse Remodeling in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    da Silva Guimarães, Sheila; de Souza Cruz, Wanise; da Silva, Licinio; Maciel, Gabrielle; Huguenin, Ana Beatriz; de Carvalho, Monicque; Costa, Bárbara; da Silva, Geisiane; da Costa, Carlos; D'Ippolito, João Alvaro; Colafranceschi, Alexandre; Scalco, Fernanda; Boaventura, Gilson

    2017-03-25

    During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. L-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of L-carnitine and increases the oxidative stress. This study demonstrates the effect of L-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with L-carnitine or group B controls. Left ventricular ejection fraction, left ventricular systolic and diastolic diameters were assessed preoperatively, 60 and 180 days after surgery. Our study included 28 patients (26 [93.0%] males) with a mean age ± SD of 58.1 ± 10.5 years. The parameters for the evaluation of reverse remodeling did not improve after 60 and 180 days of coronary artery bypass grafting in comparison between groups (p > 0.05). Evaluation within the L-carnitine group showed a 37.1% increase in left ventricle ejection fraction (p = 0.002) and 14.3% (p = 0.006) and 3.3% (p > 0.05) reduction in systolic and diastolic diameters, respectively. L-carnitine supplementation at a dose of 50 mg/kg combined with artery bypass surgery did not demonstrate any additional benefit in reverse remodeling. However, evaluation within the L-carnitine group may indicate a clinical benefit of L-carnitine supplementation.

  6. Effects of chito-oligosaccharides and L-carnitine supplementation in diets for Japanese quails on performance, carcass traits and some blood parameters

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    T. Tufan

    2015-02-01

    Full Text Available The aim of this study was to determine effects of dietary supplementation with chitosanoligosaccharides (COS and L-carnitine, individually or dually, on growth performance, carcass traits and some blood serum parameters in quails. A total of 192, four days old, Japanese quail chicks were allotted four groups, each of which included four replicates (12 birds per replicate. The groups received the same basal diet supplemented with 0 (Control, 150mg/kg chitosanoligosaccharides (COS, 150mg/kg L-carnitine (Carnitine, and 150 mg/kg chitosanoligosaccharides+150 mg/kg L-carnitine (COS+Car. during the starter (1 to 21 days and a grower (22 to 42 days period. The feeding trial shoved that COS, L-carnitine and COS+L-carnitine had no significant effect on live weight, live weight gain, feed consumption and feed conversion. Supplementation with COS+L-carnitine induced higher leg ratio from than that of the Control. There were no differences on serum albumin, total protein, glucose and total cholesterol concentrations. It is concluded that due to the obtained higher leg ratio from COS+Car. group, after analysis of the profit and loss, if is economically profitable, chitosanoligosaccharides+L-carnitine could be added quail diets.

  7. 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.

  8. Value of carnitine therapy in kidney dialysis patients and effects on cardiac function from human and animal studies.

    Science.gov (United States)

    Molyneux, Rebekah; Seymour, A-M; Bhandari, Sunil

    2012-02-01

    Cardiovascular complications are the leading cause of mortality, accounting for 50% of all deaths among patients with end-stage renal disease (ESRD). The majority of these deaths are from cardiac causes. The mechanisms underlying the enhanced susceptibility to myocardial ischaemia and subsequent morbidity in ESRD remain ill-defined. Numerous metabolic derangements accompany myocardial ischaemia and reperfusion and play a pivotal role in the development of concurrent myocardial dysfunction. Carnitine plays a critical role in myocardial energy metabolism, as the transporter of long chain fatty acyl intermediates across the inner mitochondrial membrane for β oxidation and as a central regulator of carbohydrate metabolism. Myocardial carnitine is significantly depleted during ischaemia and more particularly in uraemic patients and those on dialysis therapy. Carnitine treatment has cardiovascular benefits including modulation of myocardial metabolism, reduction in necrotic cell death and infarct size, decrease in the incidence of arrhythmias and preservation of mechanical function. This review details the profile of substrate metabolism in the uraemic heart and the impact of carnitine supplementation on metabolism and function of the reperfused heart and finally the experimental and clinical evidence for carnitine replacement therapy, in particular its impact on the uraemic heart via modulation of function and energetics.

  9. Metabolic aspects of acute cerebral hypoxia during extracorporeal circulation and their modification induced by acetyl-carnitine treatment.

    Science.gov (United States)

    Corbucci, G G; Menichetti, A; Cogliatti, A; Nicoli, P; Arduini, A; Damonti, W; Marchionni, A; Calvani, M

    1992-01-01

    Following their previous research experiences in human tissue hypoxia, in the present study the authors. investigated the metabolic effects of acute brain hypoxia in a group of patients in course of extracorporeal circulation for aorto-pulmonary bypass. One hundred subjects were treated, half with a placebo and half with acetyl-carnitine to evaluate the effects of oxidative stress in some brain plasmatic metabolites and to verify the effect of acetyl-carnitine on the tissue energy capacity. The levels of lactate, pyruvate, succinate and fumarate showed a significant imbalance due to hypoxia, while the acetyl-carnitine treatment confined the metabolic gradients within physiological limits. This means that during the course of extracorporeal circulation brain hypoxia plays a pathological role assuming the typical picture of cellular oxidative damage and the acetyl-carnitine antagonizes these deleterious effects of hypoxia by a protective mechanism on the energy processes and then on the cellular enzymic activities. In this regard, the d-tyrosine levels, considered as a proteolytic index, confirm the action of acetyl-carnitine on the cell morpho-functional integrity.

  10. Downregulation of Oxidative and Nitrosative Apoptotic Signaling by L-Carnitine in Ifosfamide-Induced Fanconi Syndrome Rat Model

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    Mohamed M. Sayed-Ahmed

    2012-01-01

    Full Text Available It is well documented that ifosfamide (IFO therapy is associated with sever nephropathy in the form of Fanconi syndrome. Although oxidative stress has been reported as a major player in IFO-induced Fanconi syndrome, no mechanism for this effect has been ascertained. Therefore, this study has been initiated to investigate, on gene expression level, the mechanism of IFO-induce nephrotoxicity and those whereby carnitine supplementation attenuates this serious side effect of IFO. To achieve the ultimate goals of this study, adult male rats were assigned to one of four treatment groups, namely, control, L-carnitine, IFO, and IFO plus L-carnitine. Administration of IFO for 5 days significantly increased serum creatinine, blood urea nitrogen (BUN, and total nitrate/nitrite (NOx production in kidney tissues. In addition, IFO significantly increased mRNA expression of inducible nitric oxide synthase (iNOS, caspase-9, and caspase-3 and significantly decreased expression of glutathione peroxides (GPx, catalase (CAT, and Bcl2 in kidney tissues. Administration of L-carnitine to IFO-treated rats resulted in a complete reversal of the all biochemical and gene expression changes, induced by IFO, to the control values. Data from this study suggest that L-carnitine prevents the development of IFO-induced nephrotoxicity via downregulation of oxidative and nitrosative apoptotic signaling in kidney tissues.

  11. L-carnitine supplementation and adipokines in patients with end-stage renal disease on regular hemodialysis.

    Science.gov (United States)

    Csiky, B; Nyul, Z; Tóth, G; Wittmann, I; Melegh, B; Rauh, M; Rascher, W; Sulyok, E

    2010-11-01

    Chronic hemodialysis (HD) patients frequently encounter carnitine depletion, elevated adipose tissue-derived hormones/cytokines, that may contribute to accelerated arteriosclerosis. 10 non-diabetic HD patients were studied over 28 weeks. In the 12 weeks treatment period 1 g L-carnitine was given iv after each HD session. Measurements of plasma free- and acylcarnitines, insulin, leptin, adiponectin, resistin and ghrelin were performed at baseline, at weeks 2, 4, 8, 12 (treatment period) and at weeks 24-28 (post-treatment period). L-carnitine supplementation resulted in progressive increase of free- and acylcarnitine levels. Plasma levels of insulin, resistin, leptin and ghrelin remained at the already elevated baseline values. L-carnitine therapy induced a significant increase in plasma adiponectin from 20.2 ± 12.7 μg/ml (baseline) to 32.7 ± 20.2 μg/ml in week 2 (pcarnitine period. Plasma insulin levels correlated positively with leptin (r = 0.525, pcarnitine status. Plasma levels of adipokines and related hormones are greatly elevated in patients on regular HD. L-carnitine administration further augmented the plasma levels of protective adiponectin, therefore it may have a role in preventing cardiovascular complications of uremia.

  12. Carnitine deficiency presenting with encephalopathy and hyperammonemia in a patient receiving chronic enteral tube feeding: a case report

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    Ling Peter

    2012-07-01

    Full Text Available Abstract Introduction Carnitine is an essential cofactor in mitochondrial fatty acid oxidation. Carnitine deficiency results in accumulation of non-oxidized fatty acyl-coenzyme A molecules, and this inhibits intra-mitochondrial degradation of ammonia. Hyperammonemia may lead to encephalopathy. This scenario has been previously reported. Case presentation We report the case of a 47-year-old Caucasian man who had sustained a remote motor vehicle accident injury and relied on long-term tube feeding with a commercial product that wascarnitine-free. He was also on phenytoin therapy for control of his chronic seizures. He developed significant acute psychological and behavioral changes superimposed on his chronic neurological impairment. His ammonia level was found to be elevated at 75 to 100μmol/L (normal Conclusion This case illustrates the importance of avoiding carnitine deficiency and anti-convulsant toxicity in tube-fed patients encountered in hospital wards and nursing homes. These patients should have their carnitine levels assessed regularly, and supplementation should be provided as necessary. Manufacturers of enteral feeds and formulas should consider adding carnitine to their product lines.

  13. Metabolic aspects of acute tissue hypoxia during extracorporeal circulation and their modification induced by L-carnitine treatment.

    Science.gov (United States)

    Corbucci, G G; Menichetti, A; Cogliatti, A; Nicoli, P; Ruvolo, C

    1992-01-01

    In this study the authors examine the effects of acute hypoxia due to extracorporeal circulation (ECC) and the role played by L-carnitine treatment on some plasmatic metabolites linked to glycolytic cellular metabolism. To obtain biochemical data, 120 patients in extracorporeal circulation during aortopulmonary bypass surgery were evaluated. The patients received either sodium bicarbonate (40 patients), or L-carnitine during ECC (40 patients) or before and during ECC (40 patients), and plasma samples were collected before ECC, during ECC and after ECC. The levels of lactate and pyruvate showed significant alterations in sodium bicarbonate-treated patients, and there was also a considerable imbalance in the succinate/fumarate ratio. This means that tissue hypoxia due to ECC leads to cellular oxidative damage and to a considerable decrease in the intracellular energy pools. The use of L-carnitine antagonizes the oxidative stress, as is well documented by the levels of plasmatic metabolites which remain confined to normal amounts.

  14. A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats.

    Science.gov (United States)

    Liang, Li-Jian; Yin, Xiao-Yu; Luo, Shi-Min; Zheng, Jin-Fang; Lu, Ming-De; Huang, Jie-Fu

    1999-08-01

    AIM:To investigate the effects of carnitine on ameliorating hepatic steatosis induced by total parenteral nutrition (TPN) in animal model.METHODS: Eighteen normal Wistar rats and 19 cirrhotic Wistar rats induced by carbon tetrachloride were randomly divided into three groups, i.e., free access to food and drink (group A), TPN (group B) and TPN+carnitine (group C) for one week, respectively. Hepatic function, histology and its fat content were determined on the 7th day.RESULTS: Hepatic triglyceride (TG) and cholesterol (CHO) contents were significantly higher in groups B and C than in group A,and significantly lower in group C than in group B in both normal and cirrhotic rats (all P Carnitine can ameliorate hepatic steatosis associated with TPN in both non-cirrhotic and cirrhotic rats.

  15. Anaesthetics modulate tumour necrosis factor α: effects of L-carnitine supplementation in surgical patients. Preliminary results.

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    Giovanna Delogu

    1993-01-01

    Full Text Available Both anaesthetics and surgical trauma could strongly affect the production of tumour necrosis factor α (TNFα. During in vitro experiments the authors found that anaesthetics modulate the production of TNFα by peripheral blood mononuclear cells. Notably, Pentothal strongly increased the production of the cytokine as compared to both lipopolysacchride treated and control mononuclear cells, whereas in supernatants from Leptofen driven mononuclear cells TNFα was strongly reduced. On the other hand, Pavulon did not significantly affect the cytokine production. In the in vivo study, in an attempt to ameliorate the metabolic response to surgical trauma, L-carnitine was administered to 20 surgical patients, then the circulating TNFα was measured. The results indicate that the levels of circulating TNFα were strongly increased following surgery and that L-carnitine administration resulted in a strong reduction of TNFα. Thus, the data suggest that L-carnitine could be helpful in protecting surgical patients against dysmetabolism dependent on dysregulated production of TNFα.

  16. Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Ferrari, Ilaria; D'Angelo, Angela; Fogari, Elena; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

    2011-10-01

    To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated the following parameters at baseline and after 3, 6, 9, and 12 months: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c) ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), adiponectin (ADN), leptin, tumor necrosis factor-α (TNF-α), vaspin, and high-sensitivity C-reactive protein (Hs-CRP). We observed a better decrease in body weight, glycemic profile, HOMA-IR, LDL-C, and ADN and a faster improvement in FPI, TC, Tg, leptin, TNF-α, Hs-CRP with orlistat plus L-carnitine compared to orlistat alone. We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone. Orlistat plus L-carnitine gave a better improvement in body weight, glycemic and lipid profile compared to orlistat alone; furthermore, a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone.

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

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    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

  18. Long-term L-Carnitine Administration reduces Erythropoietin Resistance in Chronic Hemodialysis Patients with Thalassemia Minor

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    Biagio R. Di Iorio

    2007-01-01

    Full Text Available Background and Aim: Both thalassemia and carnitine deficiency represent independent causes of erythropoietin resistance, and thus anemia, in uremic patients. We evaluated the unknown long-term effects of L-carnitine administration in β-thalassemic on chronic hemodialysis.Methods: We studied twelve subjects (M = 8; F = 4 affected by β-thalassemia minor (β-thal; HbA2 level = 6.6 ± 0.6% and forty non-thalassemic subjects (M = 24; F = 16 as controls (C, on chronic hemodialysis treatment. Patients and controls were at target hemoglobin levels (11–12g/dl prior to the study and underwent to i.v. L-carnitine administration for a one year period-time.Results: Groups were comparable for age, gender, serum levels of hemoglobin (Hb, iron, ferritine, PTH and aluminum, transferrin saturation, and dialysis modalities. During the study both groups showed signifi cant Hb increase and erythropoietin (EPO decrease; as a difference, such changes emerged at the 3rd month in C but at the 8th month in β-thal. At start, during the dialysis session the erythrocyte MCV reduced in C but not in β-thal (65.3 ± 3.2 to 65.5 ± 3.2 fl ; NS; along carnitine administration period, however, MCV during dialysis decreased also in β-thal, starting since the 9th month of treatment.Conclusion: This study provides evidence of the lowering of EPO resistance in β-thalassemia patients on hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine supplementation should be suggested to patients on dialysis affected by β-thalassemia with poorly responsive anemia, or requiring large doses of erythropoietin.

  19. L-Carnitine supplementation improved clinical status without changing oxidative stress and lipid profile in women with knee osteoarthritis.

    Science.gov (United States)

    Malek Mahdavi, Aida; Mahdavi, Reza; Kolahi, Sousan; Zemestani, Maryam; Vatankhah, Amir-Mansour

    2015-08-01

    Considering the pathologic importance of oxidative stress and altered lipid metabolism in osteoarthritis (OA), this study aimed to investigate the effect of l-carnitine supplementation on oxidative stress, lipid profile, and clinical status in women with knee OA. We hypothesized that l-carnitine would improve clinical status by modulating serum oxidative stress and lipid profile. In this randomized double-blind, placebo-controlled trial, 72 overweight or obese women with mild to moderate knee OA were randomly allocated into 2 groups to receive 750 mg/d l-carnitine or placebo for 8 weeks. Dietary intake was evaluated using 24-hour recall for 3 days. Serum malondialdehyde (MDA), total antioxidant capacity (TAC) and lipid profile, visual analog scale for pain intensity, and patient global assessment of severity of disease were assessed before and after supplementation. Only 69 patients (33 in the l-carnitine group and 36 in the placebo group) completed the study. l-Carnitine supplementation resulted in significant reductions in serum MDA (2.46 ± 1.13 vs 2.16 ± 0.94 nmol/mL), total cholesterol (216.09 ± 34.54 vs 206.12 ± 39.74 mg/dL), and low-density lipoprotein cholesterol (129.45 ± 28.69 vs 122.05 ± 32.76 mg/dL) levels compared with baseline (P .05). No significant differences were observed in dietary intake, serum lipid profile, MDA, and TAC levels between groups after adjusting for baseline values and covariates (P > .05). There were significant intragroup and intergroup differences in pain intensity and patient global assessment of disease status after supplementation (P carnitine improved clinical status without changing oxidative stress and lipid profile significantly in women with knee OA.

  20. 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

    conditions (P acetyl-CoA and acetylcarnitine were increased (P carnitine was decreased (P ...-activated protein kinase (a2-AMPK) was increased twice as much in L-CHO as in H-CHO (P acetyl-CoA carboxylase (ACC)ß Ser221 phosphorylation was increased to the same extent (6-fold) under the two conditions. The concentration of malonyl-CoA was reduced 13% by exercise in both...... of free carnitine may limit fat oxidation during exercise, due to its increased use for acetylcarnitine formation....

  1. Acetyl-l-carnitine and oxfenicine on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats.

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    Chih-Hsien Wang

    Full Text Available INTRODUCTION: In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV function. For this study, we compared the effects of acetyl-l-carnitine (one of the carnitine derivatives and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship. METHODS: Diabetes was induced by a single tail vein injection of 55 mg kg(-1 streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L(-1 in drinking water or oxfenicine (150 mg kg(-1 by oral gavage for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max and the theoretical maximum flow (Q max. Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. RESULTS: When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max. Acetyl-l-carnitine (but not oxfenicine had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q max corresponded to an increase in total vascular resistance when treated with oxfenicine. CONCLUSIONS: Acetyl-l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes

  2. Effects of dietary L-carnitine and ractopamine HCl on the metabolic response to handling in finishing pigs.

    Science.gov (United States)

    James, B W; Tokach, M D; Goodband, R D; Nelssen, J L; Dritz, S S; Owen, K Q; Woodworth, J C; Sulabo, R C

    2013-09-01

    Two experiments (384 pigs; C22 × L326; PIC) were conducted to determine the interactive effect of dietary L-carnitine and ractopamine HCl (RAC) on the metabolic response of pigs to handling. Experiments were arranged as split-split plots with handling as the main plot and diets as subplots (4 pens per treatment). Dietary L-carnitine (0 or 50 mg/kg) was fed from 36.0 kg to the end of the experiments (118 kg), and RAC (0 or 20 mg/kg) was fed the last 4 wk of each experiment. At the end of each experiment, 4 pigs per pen were assigned to 1 of 2 handling treatments. Gently handled pigs were moved at a moderate walking pace 3 times through a 50-m course and up and down a 15° loading ramp. Aggressively handled pigs were moved as fast as possible 3 times through the same course, but up and down a 30° ramp, and shocked 3 times with an electrical prod. Blood was collected immediately before and after handling in Exp. 1 and immediately after and 1 h after handling in Exp. 2. Feeding RAC increased (P 0.10) of L-carnitine on growth performance. In Exp. 1 and 2, aggressive handling increased (P blood lactate dehydrogenase (LDH), lactate, cortisol, and rectal temperature and decreased blood pH. In Exp. 1, there was a RAC × handling interaction (P blood pH and rectal temperature. Aggressively handled pigs fed RAC had decreased blood pH and increased rectal temperature compared with gently handled pigs, demonstrating the validity of the handling model. Pigs fed RAC had increased (P pigs not fed RAC. Pigs fed L-carnitine had increased (P pigs not fed L-carnitine. In Exp. 2, pigs fed RAC had lower (P blood pH immediately after handling, but pH returned to control levels by 1 h posthandling. Lactate, LDH, cortisol, and rectal temperature changes from immediately posthandling to 1 h posthandling were not different (P > 0.10) between pigs fed L-carnitine and those fed RAC, indicating that L-carnitine did not decrease recovery time of pigs subjected to aggressive handling. These

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

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    Haohai Huang

    2014-02-01

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

  4. Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats

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    Derya Selcen Salmanoglu

    2016-08-01

    Full Text Available Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks and multipl low doses intraperitoneal injection of STZ (twice, 30 mg/kg/d i.p. The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C, high fat diet (HFD, STZ-induced diabetic group (HFD+STZ , HFD+STZ diabetic group received melatonin (10 mg/kg/d i.p, HFD+STZ diabetic group received L-carnitine (0.6 g/kg/d i.p, and HFD+STZ diabetic group received glibenclamide (5 mg/kg/d, oral. The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx, superoxide dismutase (SOD and nitric oxide (NO levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes.

  5. The role of carnitine on ovariectomy and inflammation-induced osteoporosis in rats.

    Science.gov (United States)

    Orsal, Ebru; Halici, Zekai; Bayir, Yasin; Cadirci, Elif; Bilen, Habib; Ferah, Irmak; Aydin, Ali; Ozkanlar, Seckin; Ayan, Arif Kursad; Seven, Bedri; Ozaltin, Seda

    2013-12-01

    This study was carried out to assess the protective bone-sparing effect of carnitine with anti-inflammatory properties on chronic inflammation-induced bone loss in ovariectomised (OVX) rats. A total of 64 rats were divided into eight groups. Sixteen rats were sham-operated (SH) while the others were ovariectomised (OVX). (1) SH, (2) sham + inflammation (SHinf), (3) OVX, (4) ovariectomy + inflammation (OVXinf), (5) OVX + CAR1, (6) OVX + CAR2, (7) OVXinf + CAR1, (8) OVXinf + CAR2. After the ovariectomy surgery, all the groups (3, 4, 5, 6, 7, and 8) were allowed to recover for two months. Sixty days after the OVX, inflammation was induced by subcutaneous injections of talc in groups 2, 4, 7, and 8. Group 5 and 7 were given 50 mg/kg CAR; Group 6 and 8 were given 100 mg/kg CAR from the 60th to the 80th day. Serum levels of TNF-α, IL-1, IL-6, OP, and OC were assessed to determine inflammation and to evaluate osteoblastic activity. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry in femur bones of rats. Carnitine administration was able to restore BMD up to values measured in both the OVX and the SH animals. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. In OVX rats, inflammation which is evaluated by serum cytokine levels exacerbated this bone loss, as supported by values of BMD of the total femur. The two different doses of carnitine reduced bone loss and improved inflammatory biomarkers.

  6. Asymmetric synthesis of L-carnitine from (R)-3-chloro-1,2-propanediol

    Institute of Scientific and Technical Information of China (English)

    Xu Qin Li; Yun Xu Yang; Wei Li Wang; Bin Hu; Hui Min Xue; Tian Yi Zhang; Xue Tao Zhang

    2011-01-01

    A practical chemical synthesis of L-carnitine (1) has been accomplished from (R)-3-chloro-l,2-propanediol ((R)-4), which is a main by-product originated from (R,R)-Salen Co(Ⅲ) catalyzed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin. (R)-4 was utilized as a chiral starting material to prepare the key intermediate cyclic sulfite ((R)-5). The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of bioactive compounds.

  7. 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.

  8. Molecular characterization of carnitine-dependent transport of acetyl-CoA from peroxisomes to mitochondria in Saccharomyces cerevisiae and identification of a plasma membrane carnitine transporter, Agp2p.

    Science.gov (United States)

    van Roermund, C W; Hettema, E H; van den Berg, M; Tabak, H F; Wanders, R J

    1999-11-01

    In Saccharomyces cerevisiae, beta-oxidation of fatty acids is confined to peroxisomes. The acetyl-CoA produced has to be transported from the peroxisomes via the cytoplasm to the mitochondrial matrix in order to be degraded to CO(2) and H(2)O. Two pathways for the transport of acetyl-CoA to the mitochondria have been proposed. The first involves peroxisomal conversion of acetyl-CoA into glyoxylate cycle intermediates followed by transport of these intermediates to the mitochondria. The second pathway involves peroxisomal conversion of acetyl-CoA into acetylcarnitine, which is subsequently transported to the mitochondria. Using a selective screen, we have isolated several mutants that are specifically affected in the second pathway, the carnitine-dependent acetyl-CoA transport from the peroxisomes to the mitochondria, and assigned these CDAT mutants to three different complementation groups. The corresponding genes were identified using functional complementation of the mutants with a genomic DNA library. In addition to the previously reported carnitine acetyl-CoA transferase (CAT2), we identified the genes for the yeast orthologue of the human mitochondrial carnitine acylcarnitine translocase (YOR100C or CAC) and for a transport protein (AGP2) required for carnitine transport across the plasma membrane.

  9. Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding%Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    In a recent issue of PNAS, Professor Wu Donghai of Guangzhou Institutes of Biomedicine and Health (GIBH) and his colleagues published a paper titled "Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding". Prof. Wu has receivedsustained support from NSFC since 2006.

  10. Post-translational modification by acetylation regulates the mitochondrial carnitine/acylcarnitine transport protein.

    Science.gov (United States)

    Giangregorio, Nicola; Tonazzi, Annamaria; Console, Lara; Indiveri, Cesare

    2017-02-01

    The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport reaction allowing entry of acyl moieties in the form of acylcarnitines into the mitochondrial matrix and exit of free carnitine. The transport function of CACT is crucial for the β-oxidation pathway. In this work, it has been found that CACT is partially acetylated in rat liver mitochondria as demonstrated by anti-acetyl-lys antibody immunostaining. Acetylation was reversed by the deacetylase Sirtuin 3 in the presence of NAD(+). After treatment of the mitochondrial extract with the deacetylase, the CACT activity, assayed in proteoliposomes, increased. The half-saturation constant of the CACT was not influenced, while the V max was increased by deacetylation. Sirtuin 3 was not able to deacetylate the CACT when incubation was performed in intact mitoplasts, indicating that the acetylation sites are located in the mitochondrial matrix. Prediction on the localization of acetylated residues by bioinformatics correlates well with the experimental data. Recombinant CACT treated with acetyl-CoA was partially acetylated by non-enzymatic mechanism with a corresponding decrease of transport activity. The experimental data indicate that acetylation of CACT inhibits its transport activity, and thus may contribute to the regulation of the mitochondrial β-oxidation pathway.

  11. L-carnitine supplementation does not promote weight loss in ovariectomized rats despite endurance exercise.

    Science.gov (United States)

    Melton, S A; Keenan, M J; Stanciu, C E; Hegsted, M; Zablah-Pimentel, E M; O'Neil, C E; Gaynor, P; Schaffhauser, A; Owen, K; Prisby, R D; LaMotte, L L; Fernandez, J M

    2005-03-01

    In this five-week study, we tested the hypotheses that free access to a maintenance diet supplemented with L-carnitine (L-C) would reduce body fat in adult, sedentary, ovariectomized (OVX) rats, and that there would be an additive effect of L-C on weight reduction in swim-trained animals. As expected, serum carnitine was higher in rats fed the L-C diet, and the OVX-induced weight gain and abdominal fat were counteracted by swimming. L-C supplementation did not reduce the weight gain or abdominal fat in these adult female rats, Moreover, though not reaching statistical significance, rats that were fed L-C demonstrated a tendency for greater weight gain than their basal-fed counterparts despite no difference in energy intake. If the results of this study on ovariectomized rats can be translated to postmenopausal women, moderate intensity exercise may be recommended, but L-C supplementation, with no energy restriction, may be contraindicated as a weight loss method in this cohort.

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

    Energy Technology Data Exchange (ETDEWEB)

    Finocchiaro, G.; Taroni, F.; Martin, A.L.; Colombo, I.; Tarelli, G.T.; DiDonato, S. (Istituto Nazionale Neurologico C. Besta, Milan (Italy)); Rocchi, M. (Istituto G. Gaslini, Genoa (Italy))

    1991-01-15

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

  13. Severe infantile carnitine palmitoyltransferase II deficiency in 19-week fetal sibs.

    Science.gov (United States)

    Meir, Karen; Fellig, Yakov; Meiner, Vardiella; Korman, Stanley H; Shaag, Avraham; Nadjari, Michel; Soffer, Dov; Ariel, Ilana

    2009-01-01

    Antenatal presentation of carnitine palmitoyltransferase type II deficiency due to mutations in the CPT2 gene has been rarely reported. We report an Ashkenazi Jewish family with 3 terminated pregnancies for multicystic kidneys and/or hydrocephalus. Fetal autopsy after termination of the couple's 4th pregnancy (sib 2) showed renal parenchyma replaced by cysts that appeared to increase in diameter toward the medulla. Fetopsy after termination of the 7th pregnancy (sib 3) revealed micrognathia; hypospadias; cystic renal dysplasia; hepatosteatosis; and lipid accumulation in the renal tubular epithelium, myocardium, and skeletal muscle. Microvascular proliferative changes and focal polymicrogyria were seen in the brain. A beta-oxidative enzyme deficiency was suspected. CPT2 gene analysis showed a homozygous complex haplotype for the F448L mutation associated with a c.del1238_1239AG (p.Q413fs) truncating mutation in exon 4. Carnitine palmitoyltransferase type II deficiency should be included in the differential diagnosis in fetuses of Ashkenazi origin with multicystic kidneys and unusual cerebral findings.

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

    NARCIS (Netherlands)

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

    1993-01-01

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

  15. Modulation of L-arginine-induced acute pancreatitis by meloxicam and/or L-carnitine in rats

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    Mohamed I. A. Hasan

    2015-12-01

    Conclusion: Treatment with both meloxicam and L-carnitine is a more effective than each of them alone which is attributed to augmentation their antioxidant, anti inflammatory effects. [Int J Basic Clin Pharmacol 2015; 4(6.000: 1247-1253

  16. Absorption enhancement, structural changes in tight junctions and cytotoxicity caused by palmitoyl carnitine in Caco-2 and IEC-18 cells

    NARCIS (Netherlands)

    Duizer, E.; Wulp, C. van der; Versantvoort, C.H.M.; Groten, J.P.

    1998-01-01

    Palmitoyl carnitine chloride (PCC) has been shown to be an effective enhancer of intestinal transport of hydrophilic molecules. The exact mechanism by which the epithelial barrier function is decreased is not clear. In an attempt to elucidate the mechanism of action of PCC, we studied the relationsh

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

    Science.gov (United States)

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

    2013-02-15

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

  18. L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation

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    Shujue Li

    2016-08-01

    Full Text Available Background/Aims: The interactions between calcium oxalate monohydrate (COM crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. Methods: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. Results: Dedifferentiated MDCK cells induced by transforming growth factor β1 (TGF-β1 shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3β/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. Conclusions: COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3β/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis.

  19. 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

  20. Acylcarnitine ester utilization by the hindlimb of warmblood horses at rest and following low intensity exercise and carnitine supplementation

    NARCIS (Netherlands)

    Peters, L W E; Smiet, E; de Sain-van der Velden, M G M; van der Kolk, J H

    2015-01-01

    BACKGROUND: Acylcarnitines play an important role in fuel metabolism in skeletal muscle. OBJECTIVE: To assess acylcarnitine ester utilization by the hindlimb of horses at rest and following low intensity exercise and carnitine supplementation. ANIMALS AND METHODS: Acylcarnitine ester uptake by the h

  1. Carcass Traits and Immune Response of Broiler Chickens Fed Dietary L-Carnitine, Coenzyme Q10 and Ractopamine

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    H Asadi

    Full Text Available ABSTRACT This study was conducted to evaluate the effects of coenzyme Q10, L-carnitine and ractopamine supplementation, alone and in combinations, on carcass traits and immune response of broiler chickens. Five hundred and twelve one-day-old Ross 308 male broiler chickens were randomly allocated into eight treatments with four replicates each. A 2×2×2 factorial arrangement was applied, with two levels of coenzyme Q10 (0 and 40 mg/kg, two levels of L-carnitine (0 and 200 mg/kg and two levels of ractopamine (0 and 10 mg/kg. The birds were reared until day 42 of age under standard conditions. Blood samples were collected at the end of grower and finisher periods from the wing vein. Four birds per group were sacrificed at day 42 of age. Except for carcass yield, other carcass traits were not significantly affected (p>0.05 by different levels of coenzyme Q10, L-carnitine, or ractopamine. Immune response parameters were significantly (p<0.05 different between the treatments. The lowest antibody titers against Newcastle disease virus and relative spleen weight were observed in control group. The results of this study suggest that addition of coenzyme Q10 and L-carnitine to broiler diets has benefit effect on immune response of broiler chickens.

  2. L-Carnitine supplementation ameliorates serum tumor necrosis factor-alpha and matrix metalloproteinase-3 in knee osteoarthritis women

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    Reza Mahdavi

    2017-03-01

    Full Text Available Seventy-two females with mild to moderate knee osteoarthritis were included in this randomized double-blind placebo-controlled study. Patients in the intervention group (n=36 received L-carnitine supplement (750 mg/day for two months. L-Carnitine supplementation led to decrease in serum TNF-α and MMP-3 levels significantly in comparison with the baseline (p<0.001 and p<0.001, respectively and placebo group (p<0.001 and p=0.03, respectively. In addition, physician’s global assessment of the severity of osteoarthritis decreased significantly in the L-carnitine group (p<0.001 and placebo group (p=0.012 after supplementation. At the end of the study, a significant difference was observed between the two groups for mean physician’s global assessment of the severity of osteoarthritis (p<0.001, adjusted for baseline values and duration of osteoarthritis. L-Carnitine supplementation has beneficial effects in reducing inflammatory biomarkers in knee osteoarthritis patients which subsequently leads to the alleviation of disease symptoms.

  3. Short-term carnitine supplementation does not augment LCP omega 3 status of vegans and lacto-ovo-vegetarians

    NARCIS (Netherlands)

    Fokkema, MR; van Rieke, HM; Bauermann, OJ; Smit, EN; Muskiet, FAJ

    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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. L-carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal apoptosis in rat forebrain culture.

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    Wang, C; Sadovova, N; Ali, H K; Duhart, H M; Fu, X; Zou, X; Patterson, T A; Binienda, Z K; Virmani, A; Paule, M G; Slikker, W; Ali, S F

    2007-01-05

    1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with an elevation of intracellular reactive oxygen species (ROS) and apoptosis. L-carnitine plays an integral role in attenuating the brain injury associated with mitochondrial neurodegenerative disorders. The present study investigates the effects of L-carnitine against the toxicity of MPP+ in rat forebrain primary cultures. Cells in culture were treated for 24 h with 100, 250, 500 and 1000 microM MPP+ alone or co-incubated with L-carnitine. MPP+ produced a dose-related increase in DNA fragmentation as measured by cell death ELISA (enzyme-linked immunosorbent assay), an increase in the number of TUNEL (terminal dUTP nick-end labeling)-positive cells and a reduction in the mitochondrial metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). No significant effect was observed with the release of lactate dehydrogenase (LDH), indicating that cell death presumably occurred via apoptotic mechanisms. Co-incubation of MPP+ with L-carnitine significantly reduced MPP+-induced apoptosis. Western blot analyses showed that neurotoxic concentrations of MPP+ decreased the ratio of BCL-X(L) to Bax and decreased the protein levels of polysialic acid neural cell adhesion molecules (PSA-NCAM), a neuron specific marker. L-carnitine blocked these effects of MPP+ suggesting its potential therapeutic utility in degenerative disorders such as Parkinson's disease, Alzheimer's disease, ornithine transcarbamylase deficiency and other mitochondrial diseases.

  9. Ameliorative effect of acetyl-L-carnitine and/or nifedipine against selenite-induced cataractogenesis in young albino rats.

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    Farghaly, Lamiaa M; Ghobashy, Waleed A; Shoukry, Youssef; El-Azab, Mona F

    2014-04-15

    Free radical toxicity and calcium ion overload have been identified as the major two players in the causation of cataract. The current study was carried out to investigate the anti-cataractogenic effect of single and combined treatment with acetyl-l-carnitine and nifedipine in sodium selenite-induced cataract. Rat pups were divided into 5 groups; 1st group received intraperitoneal injection (i.p.) of saline and served as normal control, 2nd group received single subcutaneous injection of sodium selenite 30nmol/g body weight on p10 (postpartum day 10), 3rd and 4th groups received either acetyl-l-carnitine (200mg/kg, i.p.) or nifedipine (0.1mg/kg, i.p.) on p9, respectively, before the administration of sodium selenite, and the treatment continued till p14. Last group received the combined treatments of acetyl-l-carnitine and nifedipine in the same regimen. All animals were examined using a slit lamp and retroillumination then sacrificed on p30. Lenses were removed and processed for biochemical analyses, histopathological and electron microscopic examination. Selenite-treated groups showed significantly (P≤0.05) lower values of redox system components (glutathione and glutathione reductase activity) and anti-oxidant enzymes׳ activities (superoxide dismutase and catalase) along with increased lipid peroxidation that was accompanied by 100% opacified crystalline lenses (mature cataract) with abnormal structure as detected by electron microscopy. It is concluded that acetyl-l-carnitine or nifedipine was able to partially protect against selenite-induced abnormalities. While, combined treatment with acetyl-l-carnitine and nifedipine was superior to individual treatments in slowing down the development of cataract by restoring the anti-oxidant defense and mitigating lipid peroxidation in the lens and hence represents an attractive anti-cataractogenic remedy.

  10. 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.

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

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    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

  12. Effects of Dietary L-carnitine Supplementation on Growth Performance, Organ Weight, Biochemical Parameters and Ascites Susceptibility in Broilers Reared Under Low-temperature Environment.

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    Wang, Y W; Ning, D; Peng, Y Z; Guo, Y M

    2013-02-01

    The objective of this study was to investigate the effects of L-carnitine on growth performance, organ weight, biochemical parameters of blood, heart and liver, and ascites susceptibility of broilers at different ages reared under a low-temperature environment. A total of 420 1-d-old male Ross 308 broilers were randomly assigned to two dietary treatments with fifteen replicates of fourteen broilers each. Treatment diets consisted of L-carnitine supplementation at levels of 0 and 100 mg/kg. At 11-d of age, low temperature stress was used to increase ascites susceptibility. Blood, heart and liver samples were collected at different ages for analysis of boichemical parameters. The results showed that, there was no significant difference in growth performance with L-carnitine supplementation, but the mortality due to ascites was significantly decreased. Dietary L-carnitine supplementation significantly reduced heart index (HI) and ascites heart index (AHI) on d 21, lung index (LUI) on d 35 and liver index (LI) on d 42. The broilers fed diets containing L-carnitine had significantly lower red blood cell counts (RBC), hemoglobin (HGB) concentration and hematocrit (HCT) on d 42. Dietary L-carnitine supplementation significantly reduced malondialdehyde (MDA) content of heart tissue on d 21 and 35, and significantly increased total superoxide dismutase (T-SOD) and Glutathione peroxidase (GSH-Px) activity of the heart on d 21 and 42. L-carnitine supplementation significantly reduced serum triglyceride (TG) content on d 28 and 35 and serum glucose (GLU) on d 35 and 42, and significantly increased serum total protein (TP) and globulin (GLO) content on d 42. L-carnitine supplementation significantly enhanced liver succinodehydrogenase (SDH), malic dehydrogenase (MDH) and Na(+)-K(+)-ATPase activity on d 28, and tended to reduce the lactic acid (LD) level of liver on d 35 (p = 0.06). L-carnitine supplementation significantly reduced serum uric acid (UA) content on d 28, 35 and 42

  13. Effects of carnitine supplementation on flow-mediated dilation and vascular inflammatory responses to a high-fat meal in healthy young adults.

    Science.gov (United States)

    Volek, Jeff S; Judelson, Daniel A; Silvestre, Ricardo; Yamamoto, Linda M; Spiering, Barry A; Hatfield, Disa L; Vingren, Jakob L; Quann, Erin E; Anderson, Jeffrey M; Maresh, Carl M; Kraemer, William J

    2008-11-15

    Because carnitine has been shown to decrease oxidative stress and improve endothelial cell functioning, we examined the effects of carnitine supplementation on postprandial flow-mediated dilation (FMD) and circulating biomarkers of inflammation and oxidative stress after a high-fat meal. A randomized, double-blind, placebo-controlled, crossover study design was used. Thirty men and women (age 30 +/- 8 year, body mass 72.9 +/- 17.1 kg, body fat 13.0 +/- 6.4%) participated in 2 vascular testing days, each preceded by 3 weeks of supplementation with either 2 g/day of L-Carnitine (L-Carnitine L-Tartrate) or placebo with a 3- to 5-week washout period between trials. Brachial artery FMD in response to 5 minutes of upper arm occlusion and circulating markers of oxidative stress and inflammation were measured in the fasting state and after a standardized high-fat meal. After 3 weeks of supplementation, peak FMD in the fasting state was similar between the carnitine and placebo trials, averaging 6.6%. Peak FMD during the postprandial period decreased to 5.8% at 1.5 hours during placebo and increased to 7.7% during the carnitine trial (n = 30: p = 0.043 for supplement by time interaction effect). This improvement in postprandial vascular function was most dramatic in subjects who showed a decrease in peak FMD in response to the meal (n = 15: p = 0.003 for supplement by time interaction effect). There was a significant increase in postprandial lipemia and plasma interleukin-6 but no effect of supplementation. There were no significant postprandial changes or supplement effects for plasma tumor necrosis factor-alpha and malondialdehyde. In conclusion, consistent with other work showing a beneficial effect of carnitine on vascular function, these findings indicate that carnitine supplementation in healthy individuals improves postprandial FMD after a high-fat meal.

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

    Science.gov (United States)

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

    2016-10-29

    Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P carnitine group, 75.0%, 53.6%, and 50.0% of patients showed improvement in the FSS score, PFS, and MFS, respectively, but only 20.0%, 24.0%, and 24.0%, respectively, did so in the placebo group (all P carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

  15. Effects of supplementary dietary L-carnitine on performance and egg quality of laying hens fed diets different in fat level

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    Rahman Jahanian

    2010-02-01

    Full Text Available The present study aimed to examine the effects of dietary L-carnitine supplementation on performance parameters and egg quality measurements of white Leghorn hens at two dietary fat levels. Two hundred 22-weeks old white Leghorn hens were randomly distributed into 40 cages of five birds each. Two basal diets different in added fat level (0 or 3% were formulated and supplemented with incremental levels of L-carnitine (0, 50, 100, 150 mg/kg diet. The experiment lasted 98 d (two weeks for adaptation and 12 weeks as the main experimental period. At the final day of trial, ten randomly selected hens per treatment were euthanized to measure abdominal fat content. Dietary inclusion of 3% soybean oil caused a significant (P<0.05 increase in egg weight and egg mass, and decrease in feed consumption by the birds. Daily energy intake, however, was not affected by dietary fat supplementation. Except of feed conversion ratio, none of performance parameters were found to be influenced by dietary fat by carnitine interaction. Feed conversion ratio improved (P<0.05 when L-carnitine was supplemented to diets contained in 3% added fat. The albumen height and subsequently Haugh unit were improved (P<0.05 by dietary supplementation of L-carnitine, particularly the level of 150 mg/kg; however, eggshell quality indexes (thickness and breaking strength were not affected by dietary L-carnitine inclusion, but influenced (P<0.05 by fat supplementation of diets. Moreover, dietary addition of fat increased abdominal fat percentage and supplementary dietary L-carnitine significantly (P<0.05 decreased abdominal fat and yolk cholesterol contents. From the present results, it can be seen that although the supplemental L-carnitine had no considerable effect on most performance parameters, it had a beneficial impacts on lipid metabolism and internal egg quality indexes of 24 to 36 wk-aged laying hens.

  16. 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.

  17. Oral L-carnitine supplementation in low-birth-weight newborns: a study on neonates requiring combined parenteral and enteral nutrition.

    Science.gov (United States)

    Melegh, B; Kerner, J; Sándor, A; Vincellér, M; Kispál, G

    1986-01-01

    Effect of L-carnitine supplementation on plasma ketone body (KB) and triglyceride (TG) concentrations was studied in ten premature infants requiring combined enteral and parenteral nutrition. At the second week of life (9 to 14 days of age) the infants were randomly divided into two groups. Five of them (plasma carnitine value, 33.77 +/- 2.48 mumol/l; mean +/- SEM) received oral L-carnitine supplementation (60 mumol/kg daily) added to pasteurized pooled human milk for seven consecutive days; additional five (plasma carnitine value, 36.70 +/- 5.19 mumol/l) served as controls. Composition of the daily diet was nearly constant in the study period. On the seventh day, prior to an Intralipid infusion, plasma carnitine and ketone body levels were significantly increased in the supplemented group as compared to controls or to previous values of the same group. In response to lipid infusion the fat load induced ketone body production was significantly higher in the supplemented group as compared to controls, whereas the triglycerides reached higher levels in the control group. It is suggested that L-carnitine supplementation in low-weight newborns promotes ketone body formation from endogenous stores as well as from exogenous fat supply, and thus may enhance triglyceride utilization.

  18. 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.

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

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    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.

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

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    Ingrid M. Garrelds

    1993-01-01

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

  1. 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

  2. Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features

    Science.gov (United States)

    Lehmann, Diana; Motlagh, Leila; Robaa, Dina; Zierz, Stephan

    2017-01-01

    CPT (carnitine palmitoyltransferase) II muscle deficiency is the most common form of muscle fatty acid metabolism disorders. In contrast to carnitine deficiency, it is clinically characterized by attacks of myalgia and rhabdomyolysis without persistent muscle weakness and lipid accumulation in muscle fibers. The biochemical consequences of the disease-causing mutations are still discussed controversially. CPT activity in muscles of patients with CPT II deficiency ranged from not detectable to reduced to normal. Based on the observation that in patients, total CPT is completely inhibited by malony-CoA, a deficiency of malonyl-CoA-insensitive CPT II has been suggested. In contrast, it has also been shown that in muscle CPT II deficiency, CPT II protein is present in normal concentrations with normal enzymatic activity. However, CPT II in patients is abnormally sensitive to inhibition by malonyl-CoA, Triton X-100 and fatty acid metabolites. A recent study on human recombinant CPT II enzymes (His6-N-hCPT2 and His6-N-hCPT2/S113L) revealed that the wild-type and the S113L variants showed the same enzymatic activity. However, the mutated enzyme showed an abnormal thermal destabilization at 40 and 45 °C and an abnormal sensitivity to inhibition by malony-CoA. The thermolability of the mutant enzyme might explain why symptoms in muscle CPT II deficiency mainly occur during prolonged exercise, infections and exposure to cold. In addition, the abnormally regulated enzyme might be mostly inhibited when the fatty acid metabolism is stressed. PMID:28054946

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

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    Maria Giovanna Scioli

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

  4. Effect of exogenous insulin on plasma free carnitine levels during exercise in normal man.

    Science.gov (United States)

    Broderick, T L; Poirier, P; Tremblay, A; Catellier, C; Nadeau, A

    1989-12-01

    Preliminary data from our laboratory have shown that the decrease in plasma free carnitine levels normally found during prolonged exercise is blunted in type 1 diabetic man. This study was designed to test the hypothesis that this might be due to the sustained peripheral hyperinsulinemia seen during exercise in diabetics treated by subcutaneous insulin. Ten male subjects underwent 90 min of cycle ergometry at 60% of their maximal oxygen uptake capacity on two occasions, one with and the other without a constant 0.13 mU.kg-1.min-1 i.v. insulin infusion. Blood samples were taken at rest, during exercise, and after exercise for measurement of plasma glucose, insulin, C-peptide, free fatty acids, and carnitine. Plasma glucose dropped significantly (p less than 0.01) from basal during both infusions, but values at 30, 45, and 60 min of exercise were lower (p less than 0.05) during insulin infusion compared with the saline infusion. Exercise produced a significant (p less than 0.01) fall in plasma insulin in both infusions. However, from 30 to 90 min of exercise, the plateau insulin level was higher during the insulin infusion compared with the saline infusion (91.4 +/- 3.0 vs. 32.9 +/- 3.0 pmol/L; p less than 0.001). Plasma C-peptide decreased significantly (p less than 0.01) during exercise and recovery in both infusions, but values between infusions were not significantly different. Plasma free fatty acids increased significantly (p less than 0.01) at 90 min of exercise during the saline infusion, while during the insulin infusion this was noted during recovery only.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. 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.

  6. Simultaneous targeted analysis of trimethylamine-N-oxide, choline, betaine, and carnitine by high performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Liu, Jia; Zhao, Mingming; Zhou, Juntuo; Liu, Changjie; Zheng, Lemin; Yin, Yuxin

    2016-11-01

    Trimethylamine-N-oxide (TMAO) is a metabolite generated from choline, betaine and carnitine in a gut microbiota-dependent way. This molecule is associated with development of atherosclerosis and cardiovascular events. A sensitive liquid chromatographic electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination of TMAO related molecules including TMAO, betaine, choline, and carnitine in mouse plasma. Analytes are extracted after protein precipitation by methanol and subjected to LC-ESI-MS/MS without preliminary derivatization. Separation of analytes was achieved on an amide column with acetonitrile-water as the mobile phase. This method has been fully validated in this study in terms of selectivity, linearity, sensitivity, precision, accuracy, and carryover effect, and the stability of the analyte under various conditions has been confirmed. This developed method has successfully been applied to plasma samples of our mouse model.

  7. The protective effects of acetyl L-carnitine which added into HistidineTryptophan-Ketoglutarate solution on donor uterus

    OpenAIRE

    İlkay Demircan; Candan Özoğul; Seda Nur Akyol; Mustafa Necmi İlhan; Mustafa Kavutçu; Süreyya Barun; Mustafa Bilge; İbrahim Murat Hirfanoğlu

    2016-01-01

    Objective: At the present times uterus transplantation is an alternative therapy for women with untreatable uterine-based infertility factors. Before transplantation, the donor organ must stored in some solutions, but they may not adequate for protection. In this study, we investigated the potential protective effects of acetyl L-carnitine, added into histidine-tryptophanketoglutarate (HTK) solution, on rat uterus. Methods: We divided 24 female Wistar Albino rats into four grou...

  8. 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

  9. 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.

  10. The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

    OpenAIRE

    YÜNCÜ, MEHMET; BÜKÜCÜ, NEZAHAT; BAYAT, NURAY; SENCAR, LEMAN; Tarakçioğlu, Mehmet

    2015-01-01

    Background/aim: Methotrexate (MTX), used commonly as an antimetabolite drug in cancer therapy, leads to acute toxic side effects in tissues or organs containing rapidly dividing cells, such as bone marrow, gastrointestinal mucosa, and seminiferous tubules. In this study, we investigated the protective effects of vitamin E and L-carnitine against MTX-induced injury in rat testis. Materials and methods: Rats were divided into 4 groups, including the control group. The study took 17 days and th...

  11. Influence of L-Carnitine on fitness and oxidative stress parameters in Trotter Horses subjected to Laval’s test

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    Adalberto Falaschini

    2010-01-01

    Full Text Available In the last few years, in addition to grain, the high energy requirements of racehorses have been met with dietary supplementsof vegetable oil, which may, however, represent an easily oxidisable substrate. Carnitine can be used to improvelipid metabolism. We evaluated the changes in performance and oxidative stress parameters measured in 4 trottersreceiving a diet containing soybean oil and L-Carnitine and subjected to two Standardized Exercise Tests (SET accordingto Laval’s protocol (3 hits at increasing speed at an interval of 30 days. Blood samples were taken at rest, just aftereach of the three hits, and at 10, 20 and 40 min after each test to determine lactic acid, glucose, Non-Esterified FattyAcid (NEFA, β-hydroxybutyrate, Reactive Oxygen metabolites (ROMs, Glutathione Peroxidase (GSH-Px, and SuperoxideDismutase (SOD. L-Carnitine influenced ROMs and SOD and resulted in a reduction in the oxidative stress parameters.Some indices of the fitness status also improved.

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

    Science.gov (United States)

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

    2004-10-01

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

  13. 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.

  14. Influence of acetyl-carnitine on some mitochondrial enzymic activities in the human cerebral tissue in conditions of acute hypoxia.

    Science.gov (United States)

    Corbucci, G G; Melis, A; Piga, M; Marchionni, A; Calvani, M

    1992-01-01

    Following previous research on human tissue in conditions of acute and massive hypoxia, in the present work the authors compared the cellular enzymic response to oxidative stress in normoxic (perifocal) and hypoxic (focal) areas in human brain affected by regional acute vasculopathies. Two homogeneous groups of patients were selected following strict clinical inclusion/exclusion criteria. The groups of patients were treated with a placebo or acetyl-carnitine at same doses and following randomized, double-blind procedures. The focal areas showed a significant functional damage in lactate, pyruvate and succinate dehydrogenases and in the cytochrome oxidase activity when compared with the enzymic capacities of perifocal areas (normoxic as controls). The pretreatment with acetyl-carnitine antagonized the above-mentioned enzymic damage by a protective action linked to the endocellular energy restoration. In accordance with these data, the therapeutic role played by acetyl-carnitine in the cerebral focal hypoxia appeared to be a determinant for the cell survival mainly in the reversible phase of oxidative damage.

  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. Therapy of metabolic disorders with intravenous (IV) access ports and long term intravenous L-carnitine therapy.

    Science.gov (United States)

    Winter, S; Birek, L; Walker, T; Phalin-Roque, J; Chandler, M J; Field, C; Zorn, E

    1999-01-01

    With the expansion of newborn screening to include many organic acidurias and fatty acid oxidation defects, effective therapies of these disorders will be needed. Currently severe disorders such as methylmalonic and propionic aciduria. conventional therapy with diet and oral L-camitine often prove ineffective in preventing failure to thrive and recurrent metabolic decompensations. L-carnitine provides a natural pathway for removal of the toxic metabolites in these disorders and is life saving therapy but, with poor oral absorption (25%), it is difficult to supply adequate carnitine to meet the metabolic needs of these patients. Long term intravenous L-carnitine therapy, administered through a subcutaneous venous access port in 5 patients with organic acidurias [propionic aciduria (2), methylmalonic aciduria (2), 3 methylglutaconic aciduria(1)] resulted in improved growth, lower frequency of metabolic decompensations and increased tolerance of natural protein in the diet. An added benefit was the ability to initiate fluid. electrolytes, and antibiotics during metabolic decompensations at home thus averting hospitalizations.

  17. [Animal experiment studies on the changes in lipid and protein metabolism in L-carnitine-supplemented total parenteral nutrition].

    Science.gov (United States)

    Böhles, H; Segerer, H; Fekl, W; Stehr, K

    1983-02-01

    The influence of i.v. L-carnitine on parameters of lipid- and nitrogen metabolism was studied during total parenteral nutrition of mini pigs (x: 4077; n = 9). The infusion protocol was divided into isocaloric and isonitrogenous 48-hour-periods. Amino acids (3 g/kg/day) were administered throughout all three periods. 140 Cal/kg/day were given as non-protein calories, consisting only of glucose during period 1. During periods 2 and 3 an amount of glucose calorically equivalent to 4 g fat/kg/day was substituted with a lipid emulsion. In period 3, L-carnitine (1,5 mg/kg/day) was added. During the entire regime key parameters of fat and nitrogen metabolism were determined. During all three periods indirect calorimetry was performed and the respiratory quotient calculated. The results demonstrate a more effective lipolysis and oxydation of fatty acids during L-carnitine supplementation. This results in an increased energy gain from exogenously administered fat and a distinct improvement of nitrogen balance.

  18. Plasma and tissue levels of lipids, fatty acids and plasma carnitine in neonates receiving a new fat emulsion.

    Science.gov (United States)

    Magnusson, G; Boberg, M; Cederblad, G; Meurling, S

    1997-06-01

    This study was undertaken to compare Intralipid with a new fat emulsion containing gamma-linolenic acid and carnitine, named Pediatric Fat Emulsion 4501, in neonates with regard to lipid and carnitine metabolism over a short period of total parenteral nutrition. There were 10 neonates in each group and they tolerated the total parenteral nutrition well. In spite of the gamma-linolenic acid supplementation in the new emulsion, arachidonic acid decreased significantly in plasma lipid esters and adipose tissue in both groups after 5 d of treatment. Also, there was a decrease in plasma docosahexaenoic acid which was more pronounced in the treatment group. The relative percentage values of linoleic and linolenic acids in adipose tissue were increased, indicating that newborns have a rapid accretion of fatty acids. Plasma-triglycerides were effectively cleared during the periods without fat infusion. In the group that received Pediatric Fat Emulsion 4501 the means of both free and total plasma carnitine concentrations increased significantly, whereas they tended to decrease in the Intralipid group.

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

    Directory of Open Access Journals (Sweden)

    Arathy Saseendran

    2017-02-01

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

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

    Science.gov (United States)

    Saseendran, Arathy; Ally, K.; Gangadevi, P.; Banakar, P. S.

    2017-01-01

    Aim: To study the effect of dietary supplementation of lecithin and carnitine on growth performance and nutrient digestibility in pigs fed high-fat diet. Materials and Methods: A total of 30 weaned female large white Yorkshire piglets of 2 months of age were selected and randomly divided into three groups allotted to three dietary treatments, T1 - Control ration as per the National Research Council nutrient requirement, T2 - Control ration plus 5% fat, and T3 - T2 plus 0.5% lecithin plus 150 mg/kg carnitine. The total dry matter (DM) intake, fortnightly body weight of each individual animal was recorded. Digestibility trial was conducted toward the end of the experiment to determine the digestibility coefficient of various nutrients. Results: There was a significant improvement (p0.05) among the three treatments on average daily gain, feed conversion efficiency, and nutrient digestibility during the overall period. Conclusion: It was concluded that the dietary inclusion of animal fat at 5% level or animal fat along with lecithin (0.5%) and carnitine (150 mg/kg) improved the growth performance in pigs than non-supplemented group and from the economic point of view, dietary incorporation of animal fat at 5% would be beneficial for improving growth in pigs without dietary modifiers. PMID:28344396

  1. 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.

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

    Science.gov (United States)

    Wessels, Bart; van den Broek, Nicole M A; Ciapaite, Jolita; Houten, Sander M; Wanders, Ronald J A; Nicolay, Klaas; Prompers, Jeanine J

    2015-10-01

    Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg(-1)·day(-1) L-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by (31)P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle lipid status was determined by (1)H MRS (intramyocellular lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced insulin resistance and was associated with decreases in muscle and blood free carnitine, elevated levels of muscle lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free carnitine content, carnitine supplementation did not induce improvements in muscle lipid status, in vivo mitochondrial function, or insulin sensitivity. Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle mitochondrial dysfunction in vivo.

  3. Impact of L-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Serban, Maria-Corina; Sahebkar, Amirhossein; Mikhailidis, Dimitri P; Toth, Peter P; Jones, Steven R; Muntner, Paul; Blaha, Michael J; Andrica, Florina; Martin, Seth S; Borza, Claudia; Lip, Gregory Y H; Ray, Kausik K; Rysz, Jacek; Hazen, Stanley L; Banach, Maciej

    2016-01-12

    We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through systematic review and meta-analysis of available RCTs. The literature search included selected databases up to 31(st) January 2015. Meta-analysis was performed using fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis showed a significant reduction of Lp(a) levels following L-carnitine supplementation (WMD: -8.82 mg/dL, 95% CI: -10.09, -7.55, p carnitine (WMD: -2.91 mg/dL, 95% CI: -10.22, 4.41, p = 0.436). The results of the meta-regression analysis showed that the pooled estimate is independent of L-carnitine dose (slope: -0.30; 95% CI: -4.19, 3.59; p = 0.878) and duration of therapy (slope: 0.18; 95% CI: -0.22, 0.59; p = 0.374). In conclusion, the meta-analysis suggests a significant Lp(a) lowering by oral L-carnitine supplementation. Taking into account the limited number of available Lp(a)-targeted drugs, L-carnitine might be an effective alternative to effectively reduce Lp(a). Prospective outcome trials will be required to fully elucidate the clinical value and safety of oral L-carnitine supplementation.

  4. Effectiveness of l-carnitine supplementation in patients with erythropoietin-resistant anemia

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    Stephanie E Reuter

    2012-06-01

    Full Text Available Whilst L-carnitine (LC supplementation is recommended for the treatment of EPO-resistant anemia, the extent of effectiveness has been shown to vary considerably. Previous work by Reuter et al (2008 demonstrated a significant association between EPO-resistance and carnitine pool composition; based on these findings, it is hypothesized that patients who have a high EPO resistance index (ERI are more likely to respond to LC supplementation. Preliminary assessment of this hypothesis was conducted as retrospective analysis, using prospectively-defined criteria, of data from 2 randomized, double-blind, placebo-controlled trials. HD patients were administered LC (20 mg/kg/wk/dialysis i.v. or placebo for 24 weeks, with EPO dose and hemoglobin data assessed at Weeks 0, 12 & 24. Patients were classified as High (>0.02 μg/kg/wk/gHb or Low ERI based on baseline data. Treatment effectiveness was analyzed using %baseline ERI for all patients (Low ERI & High ERI and for High ERI patients only. 77 patients (38 LC/39 placebo were included in the analysis, of which 22 (14 LC/8 placebo were classified as High ERI. Analysis of all patient data indicated no significant differences between Week 0, 12 & 24 %baseline ERI for neither the LC nor placebo groups, whereas analysis of High ERI patient data indicated a significant reduction in %baseline ERI at Week 12 & 24 compared to Week 0 (p=0.004 for the LC treatment group, with no significant placebo treatment effect. Similarly, analysis of %baseline ERI area-under-the-curve from 0–24°weeks indicated no significant treatment effects when all patients were included in the analysis, whereas for High ERI patients, significantly lower values were demonstrated for LC vs placebo (p=0.016. These findings suggest that High ERI patients may receive the most benefit from LC supplementation. It is proposed that LC treatment results in an improvement in CPT activity via normalization of the LC/acylcarnitine ratio, thereby

  5. 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.

  6. Evidence for the participation of the stimulated sympathetic nervous system in the regulation of carnitine blood levels of soccer players during a game.

    Science.gov (United States)

    Schulpis, Kleopatra H; Parthimos, Theodore; Papakonstantinou, Evangelos D; Tsakiris, Theodore; Parthimos, Nickolaos; Mentis, Alexios-Fotios A; Tsakiris, Stylianos

    2009-08-01

    Catecholamines and carnitine blood levels are closely implicated with training. The aim of the study was to investigate the effect of sympathetic nervous system stimulation on carnitine and its fraction levels during training. Blood was obtained from 14 soccer players pregame, at intermission, and postgame. Catecholamines were measured with high-performance liquid chromatography methods; muscle enzymes creatine kinase and lactate dehydrogenase as well as lactate, pyruvate, and total antioxidant status with commercial kits; and carnitine and fraction levels with tandem mass spectrometry. Total antioxidant status (2.97 +/- 0.13 vs 0.96 +/- 0.10 mmol/L, P r = -0.51, P r = 0.58, P r = 0.49, P < .01). The significant positive correlation of adrenaline levels with total acylcarnitine and total long-chain acylcarnitine blood levels in athletes as well as the inverse correlation with free carnitine levels may indicate participation of the stimulated sympathetic nervous system in the regulation of some carnitine fraction levels during exercise.

  7. Effect of carnitine supplementation on mitochondrial enzymes in liver and skeletal muscle of rat after dietary lipid manipulation and physical activity.

    Science.gov (United States)

    Karanth, Jyothsna; Jeevaratnam, K

    2010-05-01

    Effect of carnitine supplementation in enhancing fat utilization was investigated by looking into its effects on mitochondrial respiratory enzymes activity in liver and muscle as well as on membrane fatty acid profile in rats fed with hydrogenated fat (HF) and MUFA-rich peanut oil (PO) with or without exercise. Male Wistar rats were fed HF-diet (4 groups, 8 rats in each group) or PO-diet (4 groups, 8 rats in each group), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. The PO diet as well as exercise increased the activities of mitochondrial enzymes, NADH dehydrogenase, NADH oxidase, cytochrome C reductase, cytochrome oxidase, while carnitine supplementation further augmented the oxidative capacity of both liver and muscle significantly by enhancing the activity of carnitine palmitoyl transferase and the respiratory chain enzymes. These effects can be attributed to the enhanced unsaturated fatty acids in phospholipids of mitochondria and may be due to increased fluidity of the membrane in these rats. Results of this study show a significant health promoting effects of carnitine supplementation which could be further augmented by regular exercise.

  8. 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.

  9. The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats.

    Science.gov (United States)

    Empl, Michael T; Kammeyer, Patricia; Ulrich, Reiner; Joseph, Jan F; Parr, Maria K; Willenberg, Ina; Schebb, Nils H; Baumgärtner, Wolfgang; Röhrdanz, Elke; Steffen, Christian; Steinberg, Pablo

    2015-11-01

    L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats.

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

    Directory of Open Access Journals (Sweden)

    Giuseppe Federighi

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

  11. Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency.

    Science.gov (United States)

    Korman, Stanley H; Waterham, Hans R; Gutman, Alisa; Jakobs, Cornelis; Wanders, Ronald J A

    2005-11-01

    Detection of hepatic carnitine palmitoyltransferase I (CPT IA) deficiency by metabolite screening may be problematic. The urine organic acid profile is generally said to be normal and no abnormal or increased acylcarnitine species are evident on bloodspot tandem MS examination. We diagnosed CPT IA deficiency presenting with acute encephalopathy +/- hypoglycemia and hepatomegaly in one Bukharan Jewish and two Palestinian Arab infants from consanguineous families. CPT1A mutation analysis identified two novel nonsense mutations, c.1737C>A (Y579X) and c.1600delC (L534fsX), extending the known genetic heterogeneity in this disorder. A distinctive organic aciduria was observed in all three patients, even several days after initiation of treatment and resolution of symptoms. Abnormal findings included a hypoketotic dicarboxylic aciduria with prominence of the C12 dicarboxylic (dodecanedioic) acid. This C12 dicarboxylic aciduria suggests that CPT I may play a role in uptake of long-chain dicarboxylic acids by mitochondria after their initial shortening by beta-oxidation in peroxisomes. In addition, increased excretion of 3-hydroxyglutaric acid was detected in all three patients, a finding previously observed only in glutaric aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency. Examination of urine organic acids with awareness of these metabolic findings may lead to improved diagnosis of this seemingly rare disorder.

  12. 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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    María Calderon-Dominguez

    Full Text Available 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.

  15. 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; Herrero, Laura

    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.

  16. L-Carnitine supplementation impairs endothelium-dependent relaxation in mesenteric arteries from rats.

    Science.gov (United States)

    Valgas da Silva, Carmem P; Rojas-Moscoso, Julio A; Antunes, Edson; Zanesco, Angelina; Priviero, Fernanda B M

    2014-07-01

    L-Carnitine (L-Car) is taken as fat burner. The risks of L-Car supplementation for the cardiovascular system are unclear. We evaluated the relaxing responses of the mesenteric and aorta rings from rats after four weeks of L-Car supplementation and/or physical training. Concentration response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as cyclic GMP levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) were evaluated. Physical training decreased body weight gain that was potentiated by L-Car. In mesenteric rings, L-Car impaired endothelium-dependent relaxation whereas endothelium independent relaxation was increased. In aorta, exercise improved endothelium-dependent relaxation; however, it was partially inhibited by L-Car. SNP-induced relaxation was similar in aorta of all groups. Basal cGMP were increased in aorta of exercised rats. SOD activity and MDA levels were unaltered. In conclusion, L-Car and physical exercise promotes body weight loss; however, it impairs endothelium-dependent vaso-relaxation possibly involving alterations in muscarinic receptors/eNOS/NO signalling pathway in mesenteric artery.

  17. Hormonal and nutritional regulation of muscle carnitine palmitoyltransferase I gene expression in vivo.

    Science.gov (United States)

    Liu, Hong Yan; Zheng, Guolu; Zhu, Hongfa; Woldegiorgis, Gebre

    2007-09-15

    Transgenic mice carrying the human heart muscle carnitine palmitoyltransferase I (M-CPTI) gene fused to a CAT reporter gene were generated to study the regulation of M-CPTI gene expression. When the mice were fasted for 48 h, CAT activity and mRNA levels increased by more than 2-fold in heart and skeletal muscle, but not liver or kidney. In the diabetic transgenic mice, there was a 2- to 3-fold increase in CAT activity and CAT mRNA levels in heart and skeletal muscle which upon insulin administration reverted to that observed with the control insulin sufficient transgenic mice. Feeding a high fat diet increased CAT activity and mRNA levels by 2- to 4-fold in heart and skeletal muscle of the transgenic mice compared to the control transgenic mice on regular diet. Overall, the M-CPTI promoter was found to be necessary for the tissue-specific hormonal and dietary regulation of the gene expression.

  18. Effects of L-carnitine supplementation on milk production, litter gains and back-fat thickness in sows with a low energy and protein intake during lactation.

    Science.gov (United States)

    Ramanau, A; Kluge, H; Eder, K

    2005-05-01

    The present study investigated the effect of L-carnitine supplementation during pregnancy (125 mg/d) and lactation (250 mg/d) on milk production, litter gains and back-fat thickness in sows fed a low-energy and low-protein diet during lactation. Sows supplemented with L-carnitine produced more milk on days 11 and 18 of lactation (+18 %; PLoss of body weight during lactation was similar in both groups, but sows supplemented with L-carnitine had a greater reduction of back-fat thickness (+45 %; Pcarnitine increases milk production and litter gains in sows in a strongly negative energy and N balance, and enhances body fat mobilisation.

  19. 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.

  20. Ameliorative effects of L-carnitine and vitamin E (α-tocopherol) on haematological and serum biochemical parameters in White Leghorn cockerels given ochratoxin A contaminated feed.

    Science.gov (United States)

    Abidin, Z; Khan, M Z; Khatoon, A; Saleemi, M K; Khan, A; Javed, I

    2013-01-01

    1. L-carnitine is a quaternary ammonium compound biologically synthesised from the amino acids methionine and lysine while vitamin E (α-tocopherol) is an important antioxidant. The objective of the present study was to evaluate the ameliorative effects of L-carnitine and vitamin E upon haematological and serum biochemical parameters in ochratoxin A intoxicated birds. 2. Day-old White Leghorn cockerels were acclimatised for 2 d, divided in 12 groups with 20 birds in each group. From d 3 of age, they were given different combinations of ochratoxin A (1.0 and 2.0 mg/kg), L-carnitine (1 g/kg) and vitamin E (200 mg/kg) in feed. Haematological (erythrocyte count, leucocyte count, haemoglobin concentration and haematocrit percentage) and serum biochemical parameters (serum urea, creatinine, albumin, total proteins and alanine aminotransferase) were evaluated. 3. Results confirmed that L-carnitine and vitamin E given alone or combined with 1.0 mg/kg ochratoxin A ameliorated toxin induced alterations in haematological and serum biochemical parameters. This amelioration, however, did not occur when ochratoxin of 2.0 mg/kg was given. 4. L-carnitine and vitamin E in combination have the ability to ameliorate ochratoxin altered haematological and serum biochemical parameters. However, the optimum ratio of L-carnitine + vitamin E, to be used to assure such mitigation of ochratoxin A altered changes in haematological and serum biochemical parameters in cockerels, has yet to be determined. The combination used in this study was indeed sufficient to ameliorate the alterations induced by ochratoxin A up to 1.0 mg/kg feed.

  1. 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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. 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.

  4. Deciphering the potential efficacy of acetyl-L-carnitine (ALCAR) in maintaining connexin-mediated lenticular homeostasis

    OpenAIRE

    Muralidharan, Arumugam Ramachandran; Leema, George; Annadurai, Thangaraj; Anitha, Thirugnanasambandhar Sivasubramanian; Thomas, Philip A.; Geraldine, Pitchairaj

    2012-01-01

    Purpose To determine the putative role of acetyl-L-carnitine (ALCAR) in maintaining normal intercellular communication in the lens through connexin. Methods In the present study, Wistar rat pups were divided into 3 groups of eight each. On postpartum day ten, Group I rat pups received an intraperitoneal injection (50 µl) of 0.89% saline. Rats in Groups II and III received a subcutaneous injection (50 µl) of sodium selenite (19 µmol/kg bodyweight); Group III rat pups also received an intraperi...

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

    Directory of Open Access Journals (Sweden)

    Ali Khatibjoo

    2016-08-01

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

  6. Protective effect of L-carnitine versus amifostine against cisplatin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Uzunoglu, Sernaz; Karagol, Hakan; Ozpuyan, Fulya; Cosar, Rusen; Cicin, Irfan; Yurutcaloglu, Vuslat; Denizli, Bengü; Tanriverdi, Özgür; Sut, Necdet; Kocak, Zafer

    2011-12-01

    We aimed to compare the protective effect of L-carnitine (CAR) and amifostine (AMF) against cisplatin (CDDP)-induced nephrotoxicity through biochemical markers and histopathological evaluation. Fifty-seven Wistar albino male rats were randomly classified into six groups, which were AMF+CDDP (n = 11; 200 mg/kg AMF 30 min prior to 7 mg/kg CDDP), CAR+CDDP (n = 11; 300 mg/kg CAR 30 min prior to 7 mg/kg CDDP), CDDP (n = 11; 1 mL/kg isotonic saline 30 min prior to 7 mg/kg CDDP), AMF (n = 8; 200 mg/kg AMF alone), CAR (n = 8; 300 mg/kg CAR alone), and control (n = 8; 1 mL/kg isotonic saline alone). All drugs were given intraperitoneally. Five days after medication, animals were killed, and samples of blood and kidney tissues were collected for biochemical and histopathological evaluation. The serum urea level was highest in AMF+CDDP group among CDDP-applied groups without statistical significance (median, range: 88, 56-21 mg/dL; P > 0.05). There was no statistical significance among CDDP-applied groups in terms of creatinine level (P > 0.05). In the AMF+CDDP group, the median glomerular, tubular, and tubulointerstitial inflammatory damage scores were significantly higher than the other CDDP-applied groups (P nephrotoxicity score than all the other groups (P induced nephrotoxicity. Furthermore, our findings suggest that application of AMF before CDDP may enhance CDDP-induced nephrotoxicity histopathologically.

  7. 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.

  8. Methamphetamine inhibits the glucose uptake by human neurons and astrocytes: stabilization by acetyl-L-carnitine.

    Directory of Open Access Journals (Sweden)

    P M Abdul Muneer

    Full Text Available Methamphetamine (METH, an addictive psycho-stimulant drug exerts euphoric effects on users and abusers. It is also known to cause cognitive impairment and neurotoxicity. Here, we hypothesized that METH exposure impairs the glucose uptake and metabolism in human neurons and astrocytes. Deprivation of glucose is expected to cause neurotoxicity and neuronal degeneration due to depletion of energy. We found that METH exposure inhibited the glucose uptake by neurons and astrocytes, in which neurons were more sensitive to METH than astrocytes in primary culture. Adaptability of these cells to fatty acid oxidation as an alternative source of energy during glucose limitation appeared to regulate this differential sensitivity. Decrease in neuronal glucose uptake by METH was associated with reduction of glucose transporter protein-3 (GLUT3. Surprisingly, METH exposure showed biphasic effects on astrocytic glucose uptake, in which 20 µM increased the uptake while 200 µM inhibited glucose uptake. Dual effects of METH on glucose uptake were paralleled to changes in the expression of astrocytic glucose transporter protein-1 (GLUT1. The adaptive nature of astrocyte to mitochondrial β-oxidation of fatty acid appeared to contribute the survival of astrocytes during METH-induced glucose deprivation. This differential adaptive nature of neurons and astrocytes also governed the differential sensitivity to the toxicity of METH in these brain cells. The effect of acetyl-L-carnitine for enhanced production of ATP from fatty oxidation in glucose-free culture condition validated the adaptive nature of neurons and astrocytes. These findings suggest that deprivation of glucose-derived energy may contribute to neurotoxicity of METH abusers.

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bevilacqua, M.; Vago, T.; Norbiato, G. (Servizio di Endocrinologia, Milano, (Italy))

    1991-02-01

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

  11. The Carnitine Palmitoyl Transferase (CPT) System and Possible Relevance for Neuropsychiatric and Neurological Conditions.

    Science.gov (United States)

    Virmani, Ashraf; Pinto, Luigi; Bauermann, Otto; Zerelli, Saf; Diedenhofen, Andreas; Binienda, Zbigniew K; Ali, Syed F; van der Leij, Feike R

    2015-10-01

    The carnitine palmitoyl transferase (CPT) system is a multiprotein complex with catalytic activity localized within a core represented by CPT1 and CPT2 in the outer and inner membrane of the mitochondria, respectively. Two proteins, the acyl-CoA synthase and a translocase also form part of this system. This system is crucial for the mitochondrial beta-oxidation of long-chain fatty acids. CPT1 has two well-known isoforms, CPT1a and CPT1b. CPT1a is the hepatic isoform and CPT1b is typically muscular; both are normally utilized by the organism for metabolic processes throughout the body. There is a strong evidence for their involvement in various disease states, e.g., metabolic syndrome, cardiovascular diseases, and in diabetes mellitus type 2. Recently, a new, third isoform of CPT was described, CPT1c. This is a neuronal isoform and is prevalently localized in brain regions such as hypothalamus, amygdala, and hippocampus. These brain regions play an important role in control of food intake and neuropsychiatric and neurological diseases. CPT activity has been implicated in several neurological and social diseases mainly related to the alteration of insulin equilibrium in the brain. These pathologies include Parkinson's disease, Alzheimer's disease, and schizophrenia. Evolution of both Parkinson's disease and Alzheimer's disease is in some way linked to brain insulin and related metabolic dysfunctions with putative links also with the diabetes type 2. Studies show that in the CNS, CPT1c affects ceramide levels, endocannabionoids, and oxidative processes and may play an important role in various brain functions such as learning.

  12. 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.

  13. Role of carnitine palmitoyltransferase I in the control of ketogenesis in primary cultures of rat astrocytes.

    Science.gov (United States)

    Blázquez, C; Sánchez, C; Velasco, G; Guzmán, M

    1998-10-01

    The role of carnitine palmitoyltransferase I (CPT-I) in the control of ketogenesis was studied in primary cultures of rat astrocytes. Ketone bodies were the major product of [14C]palmitate oxidation by cultured astrocytes, whereas CO2 made a minor contribution to the total oxidation products. Using tetradecylglycidate as a specific, cell-permeable inhibitor of CPT-I, a flux control coefficient of 0.77 +/- 0.07 was calculated for CPT-I over the flux of [14C]palmitate to ketone bodies. CPT-I from astrocytes was sensitive to malonyl-CoA (IC50 = 3.4 +/- 0.8 microM) and cross-reacted on western blots with an antibody raised against liver CPT-I. On the other hand, astrocytes expressed significant acetyl-CoA carboxylase (ACC) activity, and consequently they contained considerable amounts of malonyl-CoA. Western blot analysis of ACC isoforms showed that ACC in astrocytes--like in neurons, liver, and white adipose tissue--mostly comprised the 265-kDa isoform, whereas the 280-kDa isoform--which was highly expressed in skeletal muscle--showed much lower abundance. Forskolin was used as a tool to study the modulation of the ketogenic pathway in astrocytes. Thus, forskolin decreased in parallel ACC activity and intracellular malonyl-CoA levels, whereas it stimulated CPT-I activity and [14C]palmitate oxidation to both ketone bodies and CO2. Results show that in cultured astrocytes (a) CPT-I exerts a very high degree of control over ketogenesis from palmitate, (b) the ACC/malonyl-CoA/CPT-I system is similar to that of liver, and (c) the ACC/malonyl-CoA/CPT-I system is subject to regulation by cyclic AMP.

  14. 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

  15. Prevention of selenite-induced cataractogenesis by acetyl-L-carnitine: an experimental study.

    Science.gov (United States)

    Geraldine, P; Sneha, B Brijit; Elanchezhian, R; Ramesh, E; Kalavathy, C M; Kaliamurthy, J; Thomas, P A

    2006-12-01

    Several studies have suggested that antioxidants retard the process of cataractogenesis by scavenging free oxygen radicals. The present study sought to assess the efficacy of the antioxidant acetyl-L-carnitine (ALCAR) in preventing selenite-induced cataractogenesis in an experimental setting. The first, in vitro phase of the study was performed on lenses from Wistar rats incubated for 24 h at 37 degrees C in Dulbecco's Modified Eagle Medium (DMEM) alone (control, Group I), or in DMEM containing 100 microM of selenite (Group II) or in DMEM containing 100 microM of selenite and 200 microM/ml ALCAR added at the same time as selenite (Group IIIa) or 30 min, 1 h or 2 h later (Groups IIIb, IIIc and IIId, respectively). Gross morphological examination of these lenses revealed dense opacification (cataract formation) in Group II, minimal opacification in some Group IIIa lenses and no opacification in Group I. The mean activities of the antioxidant enzymes catalase and glutathione peroxidase were significantly lower in Group II than in Group I or Group IIIa lenses, while malondialdehyde concentration (an indicator of lipid peroxidation) was significantly higher in Group II lenses than that in Group I or Group IIIa lenses. The second, in vivo phase of the study revealed dense opacification (cataract formation) in 100% of Wistar rat pups receiving subcutaneous sodium selenite alone (19 microM/kg body weight) but in only 37.5% of those receiving subcutaneous selenite and intraperitoneal ALCAR. These data suggest that ALCAR is able to significantly retard experimental selenite-induced cataractogenesis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-05

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

  17. L-Carnitine supplementation decreases DNA damage in treated MSUD patients.

    Science.gov (United States)

    Mescka, Caroline Paula; Guerreiro, Gilian; Hammerschmidt, Tatiane; Faverzani, Jéssica; de Moura Coelho, Daniella; Mandredini, Vanusa; Wayhs, Carlos Alberto Yasin; Wajner, Moacir; Dutra-Filho, Carlos Severo; Vargas, Carmen Regla

    2015-05-01

    Maple syrup urine disease (MSUD) is an inherited disorder caused by severe deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their α-ketoacid derivatives. MSUD patients generally present ketoacidosis, poor feeding, ataxia, coma, psychomotor delay, mental retardation and brain abnormalites. Treatment consists of dietary restriction of the BCAA (low protein intake) supplemented by a BCAA-free amino acid mixture. Although the mechanisms of brain damage in MSUD are poorly known, previous studies have shown that oxidative stress may be involved in the neuropathology of this disorder. In this regard, it was recently reported that MSUD patients have deficiency of l-carnitine (l-car), a compound with antioxidant properties that is used as adjuvant therapy in various inborn errors of metabolism. In this work, we investigated DNA damage determined by the alkaline comet assay in peripheral whole blood leukocytes of MSUD patients submitted to a BCAA-restricted diet supplemented or not with l-car. We observed a significant increase of DNA damage index (DI) in leukocytes from MSUD patients under BCAA-restricted diet as compared to controls and that l-car supplementation significantly decreased DNA DI levels. It was also found a positive correlation between DI and MDA content, a marker of lipid peroxidation, and an inverse correlation between DI and l-car levels. Taken together, our present results suggest a role for reactive species and the involvement of oxidative stress in DNA damage in this disorder. Since l-car reduced DNA damage, it is presumed that dietary supplementation of this compound may serve as an adjuvant therapeutic strategy for MSUD patients in addition to other therapies.

  18. Investigation of inflammatory profile in MSUD patients: benefit of L-carnitine supplementation.

    Science.gov (United States)

    Mescka, Caroline Paula; Guerreiro, Gilian; Donida, Bruna; Marchetti, Desirèe; Wayhs, Carlos Alberto Yasin; Ribas, Graziela Schimitt; Coitinho, Adriana Simon; Wajner, Moacir; Dutra-Filho, Carlos Severo; Vargas, Carmen Regla

    2015-10-01

    Maple Syrup Urine Disease (MSUD) is a metabolic disorder caused by a severe deficiency of the branched-chain α-keto acid dehydrogenase complex activity which leads to the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine and valine and their respective α-keto-acids in body fluids. The main symptomatology presented by MSUD patients includes ketoacidosis, failure to thrive, poor feeding, apnea, ataxia, seizures, coma, psychomotor delay and mental retardation, but, the neurological pathophysiologic mechanisms are poorly understood. The treatment consists of a low protein diet and a semi-synthetic formula restricted in BCAA and supplemented with essential amino acids. It was verified that MSUD patients present L-carnitine (L-car) deficiency and this compound has demonstrated an antioxidant and anti-inflammatory role in metabolic diseases. Since there are no studies in the literature reporting the inflammatory profile of MSUD patients and the L-car role on the inflammatory response in this disorder, the present study evaluates the effect of L-car supplementation on plasma inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-gamma (INF-ɣ), and a correlation with malondialdehyde (MDA), as a marker of oxidative damage, and with free L-car plasma levels in treated MSUD patients. Significant increases of IL-1β, IL-6, and INF-ɣ were observed before the treatment with L-car. Moreover, there is a negative correlation between all cytokines tested and L-car concentrations and a positive correlation among the MDA content and IL-1β and IL-6 values. Our data show that L-car supplementation can improve cellular defense against inflammation and oxidative stress in MSUD patients and may represent an additional therapeutic approach to the patients affected by this disease.

  19. 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.

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

    Science.gov (United States)

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

    2017-03-01

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

  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. Effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of turkeys, hatchability of eggs and post-hatch growth of their offsprings.

    Science.gov (United States)

    Oso, A O; Fafiolu, A O; Adeleke, M A; Ladokun, O A; Sobayo, R A; Jegede, A V; Peters, S O; Oyebamiji, O A; Akinsola, J

    2014-08-01

    The effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of breeder turkeys, hatchability of eggs and post-hatch growth response was investigated using 180 breeder hens. The hens were assigned to six dietary treatments in a 2 × 3 factorial arrangements of two application modes of L-carnitine (diet and drinking water) supplemented at 0, 50 and 100 ppm (mg/kg or mg/l) levels, respectively. Each treatment was replicated five times with six hens per replicate. Dietary inclusion of 50 ppm L-carnitine showed the lowest (p plasma total cholesterol (TC) and low-density lipoprotein concentration (LDL). Breeder hens offered 50 ppm L-carnitine with no regard to application mode recorded the highest (p plasma high-density lipoprotein (HDL). Hens offered 50 and 100 ppm L-carnitine irrespective of application mode also showed reduced (p water of 100 ppm L-carnitine for breeder turkeys resulted in highest (p < 0.05) egg fertility. Offsprings from breeder hens fed diets supplemented with L-carnitine recorded no post-hatch mortality. Highest (p < 0.05) post-hatch final live weight and weight gain was obtained with poults obtained from hens fed diet supplemented with 50 ppm L-carnitine. In conclusion, dietary supplementation of 50 ppm L-carnitine for turkey hens showed improved serum lipid profile, egg fertility, reduced dead-in-shell, egg-yolk cholesterol and resulted in improved post-hatch growth performance.

  3. 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.

  4. Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise.

    Science.gov (United States)

    Hongu, N; Sachan, D S

    2000-02-01

    The effect of a combination of caffeine, carnitine and choline with or without exercise on changes in body weight, fat pad mass, serum leptin concentration and metabolic indices was determined in 20 male, 7-wk-old Sprague-Dawley rats. They were given free access to a nonpurified diet without or with caffeine, carnitine and choline at concentrations of 0.1, 5 and 11.5 g/kg diet, respectively. In a 2x2 factorial design, one-half of each dietary group was exercised, and the other half was sedentary. Body weight and food intake of all rats were measured every day for 28 d. Rats were killed and blood and tissue samples were collected and analyzed for biochemical markers. Food intake of the groups was not different, but the body weight was significantly reduced by exercise in both dietary groups. Fat pad weights and total lipids of epididymal, inguinal and perirenal regions were significantly reduced by the supplements as well as by exercise. Regardless of exercise, supplements significantly lowered triglycerides in serum but increased levels in skeletal muscle. Serum leptin concentrations were equally lowered by supplements and exercise. Serum leptin was correlated with body weight (r = 0.55, Pweight (r = 0.82, Ploss due to dietary supplements were similar to those due to mild exercise, and there were no interactive effects of the two variables.

  5. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation.

    Science.gov (United States)

    Fortin, G; Yurchenko, K; Collette, C; Rubio, M; Villani, A-C; Bitton, A; Sarfati, M; Franchimont, D

    2009-04-01

    Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C --> T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to Crohn's disease (CD). LCAR is consumed in the diet and transported actively from the intestinal lumen via the organic cation transporter OCTN2. While recognized mainly for its role in fatty acid metabolism, several lines of evidence suggest that LCAR may also display immunosuppressive properties. This study sought to investigate the immunomodulatory capacity of LCAR on antigen-presenting cell (APC) and CD4+ T cell function by examining cytokine production and the expression of activation markers in LCAR-supplemented and deficient cell culture systems. The therapeutic efficacy of its systemic administration was then evaluated during the establishment of colonic inflammation in vivo. LCAR treatment significantly inhibited both APC and CD4+ T cell function, as assessed by the expression of classical activation markers, proliferation and cytokine production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells and enhanced cytokine production. In vivo, protection from trinitrobenzene sulphonic acid colitis was observed in LCAR-treated mice and was attributed to the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR therapy may therefore represent a novel alternative therapeutic strategy and highlights the role of diet in CD.

  6. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Pooyandjoo, M; Nouhi, M; Shab-Bidar, S; Djafarian, K; Olyaeemanesh, A

    2016-10-01

    This study provides a systematic review and meta-analysis of randomized controlled trials, which have examined the effect of the carnitine on adult weight loss. Relevant studies were identified by systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials and reference lists of relevant marker studies. Nine studies (total n = 911) of adequate methodological quality were included in the review. Trials with mean difference (MD) of 95% confidence interval (CI) were pooled using random effect model. Results from meta-analysis of eligible trials revealed that subjects who received carnitine lost significantly more weight (MD: -1.33 kg; 95% CI: -2.09 to -0.57) and showed a decrease in body mass index (MD: -0.47 kg m(-2) ; 95% CI: -0.88 to -0.05) compared with the control group. The results of meta-regression analysis of duration of consumption revealed that the magnitude of weight loss resulted by carnitine supplementation significantly decreased over time (p = 0.002). We conclude that receiving the carnitine resulted in weight loss. Using multiple-treatments meta-analysis of the drugs and non-pharmacotherapy options seem to be insightful areas for research. © 2016 World Obesity.

  7. Regulatory properties of changes in the contents of coenzyme A, carnitine and their acyl derivatives in flight muscle metabolism of Locusta migratoria

    NARCIS (Netherlands)

    Worm, R.A.A.; Luytjes, W.; Beenakkers, A.M.Th.

    1980-01-01

    The concentrations of coenzyme A, carnitine and their acyl derivatives in flight muscles of the locust were determined during a two hours flight. The concentration of acetyl-CoA fell sharply immediately after the onset of flight, whereas coenzyme A level remained relatively constant. Acetylcarnitin

  8. The\tprotective\teffects\tof\tacetyl\tL-carnitine\twhich\tadded\tinto\tHistidineTryptophan-Ketoglutarate solution\ton\tdonor\tuterus

    Directory of Open Access Journals (Sweden)

    İlkay\tDemircan

    2016-12-01

    Full Text Available Objective: At\tthe\tpresent\ttimes\tuterus\ttransplantation\tis\tan\talternative\ttherapy\tfor\twomen\twith\tuntreatable uterine-based infertility\tfactors.\tBefore\ttransplantation,\tthe\tdonor\torgan\tmust\tstored\tin\tsome\tsolutions,\tbut\tthey\tmay\tnot\tadequate\tfor protection.\tIn\tthis\tstudy,\twe\tinvestigated\tthe\tpotential\tprotective\teffects\tof\tacetyl\tL-carnitine,\tadded\tinto\thistidine-tryptophanketoglutarate (HTK\tsolution,\ton\trat\tuterus. Methods: We\tdivided\t24\tfemale\tWistar\tAlbino\trats\tinto\tfour\tgroups\t(n=6.\tTheir\tuterine\ttissues\twere\tstored\tinto\tfour\tdifferent solutions\tat\tdifferent\tperiods\tat\t4oC\t;\tGroup\t1\tHTK,\t4\thours;\tGroup\t2.\tHTK\t+\tacetyl\tL- carnitine,\t4\thours,\tGroup\t3.\tHTK,\t24\thours; Group\t4.\tHTK\t+\tacetyl\tL- carnitine,\t24\thours.\tThen\ttissues\tfrom\tuterus\twere\tused\tfor\thistological\tand\tbiochemical\texamination. Results: In\tthe\tstudy\tthe\tnumber\tof\tTUNEL\tpositive\tcells\tin\tgroup\t4\twas\tlower\tthan\tgroup\t3.\tBiochemically\tevaluated\tTBARS\tand NOS\tlevels\twere\thighest\tin\tgroup\t3\thowever\tCAT\tlevel\twas\thighest\tin\tgroup\t2. Conclusion: In\tconclusion,\taddition\tof\tacetyl\tL-carnitine\tto\tHTK\tsolution\treversed\tthe\thistological\talterations\tafter\t24\thours\tcold storage\ton\trat\tuterus.

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

    Science.gov (United States)

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

    2011-01-01

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

  10. 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.

  11. Effect of 8-day therapy with propionyl-L-carnitine on muscular and subcutaneous blood flow of the lower limbs in patients with peripheral arterial disease.

    Science.gov (United States)

    Bolognesi, M; Amodio, P; Merkel, C; Godi, L; Gatta, A

    1995-09-01

    The efficacy of propionyl-L-carnitine in increasing walking capacity in patients with peripheral arterial disease is primarily due to the metabolic effect of the drug, but a direct vasoactive action is also hypothesized. Muscular and subcutaneous blood flow of lower limbs were separately evaluated using the 133-Xenon washout technique in 10 patients with peripheral arterial disease of moderate degree, before and after 8-days of treatment with propionyl-L-carnitine (1 g orally b.i.d.). After treatment, muscular blood flow slightly increased, from 10.7 +/- 13.4 to 14.1 +/- 14.0 ml kg-1 min-1. This increase was not statistically significant (T = -1.6568, P = 0.136). Subcutaneous blood flow was not affected by the treatment (from 26.2 +/- 16.9 to 26.1 +/- 12.5 ml kg-1 min-1, T = 0.0141, P = 0.95). In conclusion, in patients with peripheral arterial disease, short-term therapy with propionyl-L-carnitine had no clinical significant effect on muscular and subcutaneous blood flow of the lower limbs. Therefore, this study suggests that the beneficial effect of this drug on the walking capacity of patients with peripheral arterial disease is not due to a direct vasoactive action. Oral administration of propionyl-L-carnitine was found to be safe, as it did not cause any change in heptic, renal or metabolic functional parameters.

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

    NARCIS (Netherlands)

    Wessels, Bart; van den Broek, Nicole M A; Ciapaite, Jolita; Houten, Sander M; Wanders, Ronald J A; Nicolay, Klaas; Prompers, Jeanine J

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ebru ÇETİN

    2004-12-01

    Full Text Available This İnvestigation examined the effect of creatin and carnitine supplementation on 5 km classic and 10 km free styles race performance of competitive cross country skiers.Eighteen highly trained (12 male and 6 female cross country skiers aged 13-16 years seperated into 3 equal groups. All groups participated in the 5 km classic and 10 km free races styles in Erciyes at 2200m altitude ski center before the carnitine and creatine loading. After the race subjects were seperated into carnitine, creatine and control groups. Creatine supplementation was given with the dosege of 20gr divided 4 times per day and carnite wasgicen with the dossage of 2gr divided 3 times per day, for seven days.After the last race all results were analysed by repeated measure analysis of variance and SPSS statistical program.According to the study there were no significant effects of carnitin and creatin supplement on 5 km classic and 10 km free styles race performans as in groups. The increased performances which were reperted can be explained by 9 days aerobic, on competition course.

  14. Transport of L-carnitine in human corneal epithelial cells%左旋肉碱在人角膜缘上皮细胞的转运特性

    Institute of Scientific and Technical Information of China (English)

    李宝全; 毕建成; 安翠平; 李延峰; 许顺江

    2015-01-01

    Objective To investigate the characteristics of L-carnitine (LC)import into human corneal limbal epithelia (HCLE)cells,and to provide an experimental basis for further study of transport mechanism of LC in human ocular epithelium.Methods The transport of [3 H ]-L-carnitine was determined using the radio uptake assay and the apparent kinetic parameters of carnitine uptake by HCLE were estimated by nonlinear regression curve fitting according to the Michaelis-Menten equation.Results The uptake of LC into HCLE cells was saturable and time-dependent,and it also required the presence of Na+ in the external medium.An Eadie-Hofstee plot showed two distinct components:a high-and a low-affinity carnitine transport system in HCLE cells.The unlabelled LC and acetyl-L-carnitine competitively inhibited the uptake of [3 H]-L-carnitine by HCLE cells.Conclusion L-carnitine is transported into HCLE cells from tears by an active carrier mediated transport system and exerts its biological function.%目的:检测左旋肉碱(L-carnitine,LC)在人角膜缘上皮(human corneal limbal epithelia,HCLE)细胞的转运特性,为进一步阐明 HCLE细胞对 LC的转运机制提供实验依据。方法采用放射摄入实验检测 HCLE细胞对[3 H]-L-carnitine的转运功能,并利用米氏方程(Michaelis-Menten equation)分析计算其动力学参数。结果HCLE细胞对 LC的转运过程具有饱和性和时间依赖性,并且反应体系中需要 Na+的存在。Eadie-Hofstee作图提示 HCLE细胞存在高亲和力和低亲合力2个肉碱转运系统。非标记 LC和乙酰化左旋肉碱可竞争性抑制[3 H]-L-carnitine的转运过程。结论 HCLE细胞可通过主动转运过程将泪液中的左旋肉碱摄入细胞内,发挥其生物学功能。

  15. 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.

  16. L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study

    Directory of Open Access Journals (Sweden)

    Cruciani RA

    2015-02-01

    Full Text Available Ricardo A Cruciani,1 Manuel Revuelta,2 Ella Dvorkin,3 Peter Homel,4 Pauline Lesage,5 Nora Esteban-Cruciani6 1Center for Comprehensive Pain Management and Palliative Care, Capital Institute for Neurosciences, Capital Health Medical Center, Pennington, NJ, 2Lee Memorial Hospital, Fort Myers, FL, 3Institutional Review Board, New York University, New York, NY, 4Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY, 5Maimonides Medical Center, Brooklyn, NY, 6Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA Background: The purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS. Methods: In this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count. Results: Eighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001 and from 24±8 to 40±13 nM/L (P<0.001 respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L and increased

  17. 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.

  18. 原发性肉碱缺乏症诊治进展%Progresses of in diagnosis and treatment of primary carnitine deficiency

    Institute of Scientific and Technical Information of China (English)

    黄倬

    2012-01-01

    Primary carnitine deficiency is a fatty acid oxidation disorder caused by mutations in the SLC22A5 gene. The role of carnitine is to help the long-chain fatty acids cross the inner mitochondrial membrane for subsequent p-oxidation. Carnitine deficiency results in decreased energy production and fatty acids accumulation in the cytosol. especially when fatty acids mobilized from adipose tissue become the predominant energy source, which can lead to metabolic disturbance and organic damage. The clinical manifestations include hypoketotie hypoglyccmia, dilated cardiomyopathy, lipid storage myopathy, hepatomegaly, and so on. Diagnosis of the disease relies on the measurement of blood free carnitine and acylcarnitines by tandem mass spectrometry, and SLC22A5 gene mutation test. L-carnitine is the main drug for this disease and, the majority of patients can fully recover after treatment.%原发性肉碱缺乏症是SLC22A5基因突变所致的脂肪酸氧化代谢病.肉碱缺乏导致长链脂肪酸不能进入线粒体参与β氧化,尤其当机体需要脂肪动员供能时不能提供足够能量,且脂肪酸蓄积在细胞内,引起代谢紊乱和脏器损伤,临床上可出现低酮型低血糖、扩张型心肌病、脂质沉积性肌病、肝肿大等.诊断依靠串联质谱检测血游离肉碱、酰基肉碱水平及基因突变检测.左旋肉碱是治疗该病的主要药物,大部分患者治疗后可完全恢复健康.

  19. The Effect of Oral L-Carnitine Supplementation on Lipid Profiles and Antioxidant Status in Hemodialysis Patients: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    S Ahmadi

    2016-04-01

    Full Text Available Introduction: Dyslipidemia and oxidative stress are commonly seen in the patients undergoing hemodialysis. This study aimed to evaluate the effect of oral L-carnitine supplementation on lipid profiles and total antioxidant capacity of the patients were treated with hemodialysis. Methods: This study was a randomized, controlled clinical trial. The participants of this study consisted of 50 hemodialysis patients in dialysis centers of Yazd between 2013 and 2014. The patients randomly divided into two groups; L-carnitine (LG and control group (CG. The patients in the LG were instructed to use daily 1g L-carnitine oral supplementation, as syrup for 12 weeks. The patients in the CG did not receive any supplement containing L-carnitine. At the baseline and the end of 12 weeks, triglycerides, total cholesterol (TC, LDLc, and total antioxidant capacity of serum (TAC were evaluated in both groups. Results: The mean of triglyceride and TC between and within groups were not significantly different. The mean of LDLc did not change in LG whereas a significant increase was seen in CG (p=0.02. The mean differences of LDLc between groups was statistically significant (p=0.05. No Significant changes were observed in serum levels of TAC in LG compared with CG (p=0.76. TAC was increased in both groups, but these changes were not statistically significant (p=0.62. Conclusions: This study showed that oral supplementation of L-carnitine as syrup (1g per day for 12 weeks among the hemodialysis patients would have no effect on triglyceride, TC, and TAC, but it would decrease the LDLc.

  20. 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.)

  1. Results of a single blind, randomized, placebo-controlled clinical trial to study the effect of intravenous L-carnitine supplementation on health-related quality of life in Indian patients on maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Rathod Rahul

    2006-04-01

    Full Text Available Background: Carnitine insufficiency is responsible for various co-morbid conditions in maintenance hemodialysis (MHD patients. L-carnitine supplementation is expected to improve the quality of life (QoL of patients on MHD. Aims: To study the effect of L-carnitine supplementation on QoL of Indian patients on MHD. Setting and Design: This was a single (patient blind, randomized, placebo-controlled clinical trial conducted on patients on MHD attending hemodialysis unit of the study center. MaterialS and Methods: Twenty patients on MHD suffering from hemodialysis-related symptoms were randomly assigned to receive intravenous L-carnitine 20 mg/kg or placebo after every dialysis session for 8 weeks. SF36 (Short Form with 36 questions score for QoL, laboratory investigations and dialysis related symptoms were recorded at baseline and after 8 weeks. Improvement in QoL, laboratory parameters and dialysis related symptoms in the two groups after 8 weeks was compared. Statistical analysis used: Depending on normality of data, unpaired T test or Mann Whitney U test was used for comparison of change (8 weeks-baseline in SF36 scores and laboratory parameters observed in the two groups. Results: L-carnitine supplementation increased total SF36 score by 18.29 ± 12.71 (95% CI: 10.41 to 26 while placebo resulted in reduction in total SF36 score by 6.4 ± 16.39 (95% CI: -16.59 to 3.73. L-carnitine also resulted in significant increase in hemoglobin and serum albumin and decrease in serum creatinine as compared to placebo. More patients were relieved of dialysis related symptoms in L-carnitine group. Conclusion: Intravenous L-carnitine supplementation improves QoL in patients on MHD.

  2. Intense Exercise and Aerobic Conditioning Associated with Chromium or L-Carnitine Supplementation Modified the Fecal Microbiota of Fillies

    Science.gov (United States)

    Feringer, Walter Heinz; Carvalho, Júlia Ribeiro Garcia; Rodrigues, Isadora Mestriner; Jordão, Lilian Rezende; Fonseca, Mayara Gonçalves; Carneiro de Rezende, Adalgiza Souza; de Queiroz Neto, Antonio; Weese, J. Scott; da Costa, Márcio Carvalho

    2016-01-01

    Recent studies performed in humans and rats have reported that exercise can alter the intestinal microbiota. Athletic horses perform intense exercise regularly, but studies characterizing horse microbiome during aerobic conditioning programs are still limited. Evidence has indicated that this microbial community is involved in the metabolic homeostasis of the host. Research on ergogenic substances using new sequencing technologies have been limited to the intestinal microbiota and there is a considerable demand for scientific studies that verify the effectiveness of these supplements in horses. L-carnitine and chromium are potentially ergogenic substances for athletic humans and horses since they are possibly able to modify the metabolism of carbohydrates and lipids. This study aimed to assess the impact of acute exercise and aerobic conditioning, associated either with L-carnitine or chromium supplementation, on the intestinal microbiota of fillies. Twelve “Mangalarga Marchador” fillies in the incipient fitness stage were distributed into four groups: control (no exercise), exercise, L-carnitine (10g/day) and chelated chromium (10mg/day). In order to investigate the impact of acute exercise or aerobic conditioning on fecal microbiota all fillies undergoing the conditioning program were analyzed as a separate treatment. The fillies underwent two incremental exercise tests before and after training on a treadmill for 42 days at 70–80% of the lactate threshold intensity. Fecal samples were obtained before and 48 h after acute exercise (incremental exercise test). Bacterial populations were characterized by sequencing the V4 region of the 16S rRNA gene using the MiSeq Illumina platform, and 5,224,389 sequences were obtained from 48 samples. The results showed that, overall, the two most abundant phyla were Firmicutes (50.22%) followed by Verrucomicrobia (15.13%). The taxa with the highest relative abundances were unclassified Clostridiales (17.06%) and "5 genus

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. 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.

  6. 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.

  7. The effect of acetyl-L-carnitine on lenticular calpain activity in prevention of selenite-induced cataractogenesis.

    Science.gov (United States)

    Elanchezhian, R; Sakthivel, M; Geraldine, P; Thomas, P A

    2009-05-01

    The present study sought to determine whether acetyl-L-carnitine (ALCAR) prevents selenite cataractogenesis by mechanisms involving lenticular calpain activity, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; Group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19micromol/kg body weight) on postpartum day 10; Group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of acetyl-L-carnitine (200mg/kg body weight) on postpartum days 9-14. At the end of the study period (postpartum day 16), both eyes of each rat pup were examined by slit-lamp biomicroscopy. There was dense lenticular opacification in all Group II rats, minimal lenticular opacification in 33% of Group III rats, and no lenticular opacification in 67% of Group III and in all Group I rats. Group II lenses exhibited significantly lower mean values of calpain activity and Lp82 (lens-specific calpain) protein expression, decreases in relative transcript level of m-calpain mRNA and significantly higher mean Ca(2+) concentrations than Group I or Group III lenses; the values of these parameters in Group III rat lenses (ALCAR-treated) approximated those in Group I rat lenses. The results suggest that, in addition to its already-described antioxidant potential, ALCAR prevents selenite cataractogenesis by maintaining calpain activity at near normal levels. These findings may stimulate further efforts to develop ALCAR as a novel drug for prevention of cataract.

  8. Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men

    Directory of Open Access Journals (Sweden)

    Smith Webb A

    2007-12-01

    Full Text Available Abstract We have recently demonstrated that oral intake of glycine propionyl-L-carnitine (GPLC increases plasma nitrate/nitrite (NOx, a surrogate measure of nitric oxide production. However, these findings were observed at rest, and in previously sedentary subjects. Purpose In the present study, we sought to determine the impact of oral GPLC on plasma NOx at rest and in response to a period of reactive hyperemia in resistance trained men. Methods Using a double blind, crossover design, 15 healthy men (24 ± 4 years were assigned to GPLC (3 g/d PLC + 1044 mg glycine and a placebo in random order, for a four-week period, with a two-week washout between condition assignment. Blood samples were taken from subjects at rest and at 0, 3, and 10 minutes following an ischemia-reperfusion protocol (six minutes of upper arm cuff occlusion at 200 mmHg followed by rapid reperfusion with cuff removal. Blood samples were taken from a forearm vein from the same arm used for the protocol and analyzed for total nitrate/nitrite. Data are presented as mean ± SEM. Results A condition main effect (p = 0.0008 was noted for NOx, with higher values in subjects when using GPLC (45.6 ± 2.8 μmol·L-1 compared to placebo (34.9 ± 1.2 μmol·L-1. No time main effect was noted (p = 0.7099, although values increased approximately 12% from rest (37.7 ± 2.7 μmol·L-1 to a peak at 10 minutes post protocol (42.3 ± 3.3 μmol·L-1. The interaction effect was not significant (p = 0.8809, although paired time contrasts revealed higher values for GPLC compared to placebo at 3 (48.2 ± 6.7 vs. 34.9 ± 2.4 μmol·L-1; p = 0.033 and 10 (48.8 ± 5.9 vs. 35.7 ± 2.1 μmol·L-1; p = 0.036 minutes post protocol, with non-statistically significant differences noted at rest (41.8 ± 4.5 vs. 33.6 ± 2.5 μmol·L-1; p = 0.189 and at 0 minutes (43.6 ± 5.1 vs. 35.4 ± 2.7 μmol·L-1; p = 0.187 post protocol. An analysis by subject (collapsed across time indicated that 11 of the 15 subjects

  9. 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

  10. 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

  11. L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study

    OpenAIRE

    Zhang, Jun-Jie; Wu, Zhi-bing; Cai, You-jin; Ke, Bin; Huang, Ying-juan; Qiu, Chao-ping; Yang, Yu-bing; Shi, Lan-Ying; QIN, JIAN

    2014-01-01

    Background The present study aimed to determine that whether L-carnitine infusion could ameliorate fasting-induced adverse effects and improve outcomes. Method In this 7-day, randomized, single-blind, placebo-controlled, pilot study, 15 metabolic syndrome (MetS) patients (11/4 F/M; age 46.9 ± 9.14 years; body mass index [BMI] 28.2 ± 1.8 kg/m2) were in the L-carnitine group (LC) and 15 (10/5 F/M; age 46.8 ± 10.9 years; BMI 27.1 ± 2.3 kg/m2) were in the control group (CT). All participants unde...

  12. Evaluation of the antineoplastic activity of mitoxantrone-L-carnitine combination therapy on an experimental solid form of ehrlich tumour in mice.

    Science.gov (United States)

    Niang, M; Melka, M; Stoklasová, A; Cerman, J; Tomsík, P

    2006-12-01

    We have commenced a series of experiments to evaluate the effect of carnitine derivatives on the antineoplastic activity of mitoxantrone (MX) on various animal cancers. This report describes the therapeutic effect of MX in combination with l-carnitine (LCAR) on the growth of a solid form of Ehrlich tumour inoculated into mice. LCAR was administered subcutaneously at doses of either 200 or 100mgkg(-1) on day 6 and 13 after tumour inoculation, 1h prior to the treatment with MX. Mitoxantrone was administered intravenously at doses of 3 or 6mgkg(-1). We found that LCAR had no potentiating effect on the efficacy of MX, in terms of either slowing tumour growth or increasing the survival of mice. Nevertheless, therapeutic effects can be assumed at higher doses of both drugs based on values calculated from an index of relative hazards.

  13. Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure.

    Science.gov (United States)

    Tolu, Pierluigi; Masi, Flavio; Leggio, Benedetta; Scheggi, Simona; Tagliamonte, Alessandro; De Montis, M Graziella; Gambarana, Carla

    2002-09-01

    Acetyl-L-carnitine (ALCAR) is the acetyl ester of carnitine that has been reported to be beneficial in depressive disorders and Alzheimer's disease. A 7-day administration of ALCAR in rats increased dopamine and serotonin output in the nucleus accumbens shell and it prevented the development of escape deficit produced by acute exposure to unavoidable stress. No tolerance developed to this protective effect, which appeared to be mediated by (1) the activation of 5-HT(1A) receptors, as it was antagonized by the administration of WAY100635 30 min before stress exposure; and (2) a process of neuronal plasticity dependent on NMDA receptor activity, as subcutaneous dizocilpine infusion during ALCAR treatment prevented the development of the protective effect on stress. Chronic stress exposure maintains an escape deficit condition that is reverted by a long-term treatment with antidepressants, but the same condition was not modified by long-term ALCAR administration. Thus, ALCAR cannot be defined as an antidepressant.

  14. 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.

  15. Effects of chito-oligosaccharides and L-carnitine supplementation in diets for Japanese quails on performance, carcass traits and some blood parameters

    OpenAIRE

    T. Tufan; Arslan,C.; Ö. Durna; ÖNK, K.; SARI, M.; Erman,H.

    2015-01-01

    The aim of this study was to determine effects of dietary supplementation with chitosanoligosaccharides (COS) and L-carnitine, individually or dually, on growth performance, carcass traits and some blood serum parameters in quails. A total of 192, four days old, Japanese quail chicks were allotted four groups, each of which included four replicates (12 birds per replicate). The groups received the same basal diet supplemented with 0 (Control), 150mg/kg chitosanoligosaccharides (COS), 150mg/kg...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-07-30

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

  17. 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.

  18. L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs

    Directory of Open Access Journals (Sweden)

    Borghi-Silva A.

    2006-01-01

    Full Text Available The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease (COPD patients. Sixteen COPD patients (66 ± 7 years were randomly assigned to L-carnitine (CG or placebo group (PG that received either L-carnitine or saline solution (2 g/day, orally for 6 weeks (forced expiratory volume on first second was 38 ± 16 and 36 ± 12%, respectively. Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions, with 3 sets of 10 loaded inspirations (40% at maximal inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and six-minute walking test, blood lactate, heart rate, blood pressure, and respiratory muscle strength were determined as baseline and on day 42. Maximal capacity in the incremental exercise test was significantly improved in both groups (P < 0.05. Blood lactate, blood pressure, oxygen saturation, and heart rate at identical exercise levels were lower in CG after training (P < 0.05. Inspiratory muscle strength and walking test tolerance were significantly improved in both groups, but the gains of CG were significantly higher than those of PG (40 ± 14 vs 14 ± 5 cmH2O, and 87 ± 30 vs 34 ± 29 m, respectively; P < 0.05. Blood lactate concentration was significantly lower in CG than in PG (1.6 ± 0.7 vs 2.3 ± 0.7 mM, P < 0.05. The present data suggest that carnitine can improve exercise tolerance and inspiratory muscle strength in COPD patients, as well as reduce lactate production.

  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. 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.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  2. 分光光度法检测保健茶中左旋肉碱%Determination of L-carnitine in sanitarian tea with spectrophotometry

    Institute of Scientific and Technical Information of China (English)

    金世梅; 赵志红; 朱慧; 吴伟都

    2011-01-01

    样品经稀释后,游离态的左旋肉碱与乙酰辅酶A在肉碱乙酰转移酶的催化下反应生成乙酰肉碱和游离的辅酶A,游离的辅酶A和5,5′-二硫-2-硝基苯甲酸反应生成黄色物质,其颜色深浅与游离的辅酶A含量成正比,采用分光光度法检测,方法重现性好(RSD,0.142%),回收率也很高(96.2%~108.0%)。%After sample was diluted,L-carnitine in free state interacts with acetyl coenzyme A into acetyl carnitine and free coenzyme A by the catalysis of carnitine acetyltransferase.Free coenzyme A reacts with 5,5′-disulfide-2-nitrobenzoic acid into yellow substance and its depth of color is proportional to the content of free coenzyme A.This method has a good reproducibility(RSD,0.142%)and high recovery(96.2%~108.0%).

  3. Ethnic-specific splicing mutation of the carnitine-acylcarnitine translocase gene in a Chinese neonate presenting with sudden unexpected death

    Institute of Scientific and Technical Information of China (English)

    林青云; 赖志刚; 周镇邦; 汤瑞芳; 袁月冰; 麦婉芳; 陈恩和

    2003-01-01

    Carnitine-acylcarnitine translocase (CACT) deficiency (OMIM 212138) is an autosomal recessive disease caused by mutations of the SLC25A20 gene [solute carrier family 25 (carnitine/acylcarnitine translocase), member 20]. The gene has an open reading frame of 903 bp,1 mapped to chromosome 3p21.31 by in situ hybridization,2 and encodes a protein having three repeated homologous domains, each about 100 amino acids in length-a characteristic feature of mitochondrial transport proteins.3,4 CACT is essential in long-chain fatty acid oxidation because CACT is located in the inner side of the inner mitochondrial membrane, shuttling long-chain acylcarnitines in the intermembranous space against carnitine in the mitochondrial matrix. The first patient with CACT deficiency reported in the United States,5 and the first patient reported in the United Kingdom6 are both of mixed ethnicity with one of the parents being Chinese. Intriguingly, there is no single case of CACT deficiency reported in Chinese populations, suggesting that this disease may be underdiagnosed in Chinese populations. In this study, we have confirmed that CACT deficiency can be a cause of sudden neonatal death in Chinese.

  4. Acetyl L-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos.

    Science.gov (United States)

    Cuevas, Elvis; Trickler, William J; Guo, Xiaoqing; Ali, Syed F; Paule, Merle G; Kanungo, Jyotshna

    2013-01-01

    Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple studies have shown ketamine to be neurotoxic, particularly when administered during the brain growth spurt. Previously, we have shown that ketamine is detrimental to motor neuron development in the zebrafish embryos. Here, using both wild type (WT) and transgenic (hb9:GFP) zebrafish embryos, we demonstrate that ketamine is neurotoxic to both motor and sensory neurons. Drug absorption studies showed that in the WT embryos, ketamine accumulation was approximately 0.4% of the original dose added to the exposure medium. The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These results suggest that acetyl L-carnitine protects both motor and sensory neurons from ketamine-induced neurotoxicity.

  5. 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.

  6. L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kira, Yukimi; Nishikawa, Manabu; Ochi, Akemi; Sato, Eisuke; Inoue, Masayasu

    2006-01-27

    Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by progressive degeneration of motor neurons in the spinal cord and motor cortex. Although the etiology of ALS remains unknown, a mutation of the gene encoding Cu,Zn-superoxide dismutase (SOD1) has been reported in 20% of familial cases of ALS (FALS). Transgenic mice that overexpress a mutated human SOD1 exhibit a phenotype and pathology similar to those observed in patients with FALS. Mitochondrial abnormality has been reported in patients with ALS and in animal models of FALS. We recently reported that L-carnitine, an essential cofactor for the beta-oxidation of long-chain fatty acids, effectively inhibits various types of mitochondrial injury and apoptosis both in vitro and in vivo. The present study demonstrates that oral administration of L-carnitine prior to disease onset significantly delayed the onset of signs of disease (log-rank P=0.0008), delayed deterioration of motor activity, and extended life span (log-rank P=0.0001) in transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg). More importantly, subcutaneous injection of L-carnitine increased the life span of Tg mice (46% increase in male, 60% increase in female) even when given after the appearance of signs of disease.

  7. l-Carnitine l-tartrate supplementation favorably affects biochemical markers of recovery from physical exertion in middle-aged men and women.

    Science.gov (United States)

    Ho, Jen-Yu; Kraemer, William J; Volek, Jeff S; Fragala, Maren S; Thomas, Gwendolyn A; Dunn-Lewis, Courtenay; Coday, Michael; Häkkinen, Keijo; Maresh, Carl M

    2010-08-01

    The purpose of this study was to examine the effects of Carnipure tartrate (Lonza, Allendale, NJ) supplementation (total dose of 2 g/d of l-carnitine) on markers of performance and recovery from physical exertion in middle-aged men and women. Normally active and healthy men (n = 9, 45.4 +/- 5.3 years old) and women (n = 9, 51.9 +/- 5.0 years old) volunteered to participate in the investigation. Double-blind, placebo, balanced treatment presentation and crossover design were used with 3 weeks and 3 days of supplementation followed by a 1-week washout period before the other counterbalanced treatment was initiated. After 3 weeks of each supplementation protocol, each participant then performed an acute resistance exercise challenge of 4 sets of 15 repetitions of squat/leg press at 50% 1-repetition maximum and continued supplementation over the recovery period that was evaluated. Blood samples were obtained at preexercise and at 0, 15, 30, and 120 minutes postexercise during the acute resistance exercise challenge and during 4 recovery days as well. Two grams of l-carnitine supplementation had positive effects and significantly (P supplementation. These findings support our previous findings of l-carnitine in younger people that such supplementation can reduce chemical damage to tissues after exercise and optimize the processes of muscle tissue repair and remodeling.

  8. Antioxidant effects of carnitine supplementation on 14-3-3 protein isoforms in the aged rat hippocampus detected using fully automated two-dimensional chip gel electrophoresis.

    Science.gov (United States)

    Iwamoto, M; Miura, Y; Tsumoto, H; Tanaka, Y; Morisawa, H; Endo, T; Toda, T

    2014-12-01

    We here described the antioxidant effects of carnitine supplementation on 14-3-3 protein isoforms in the aged rat hippocampus detected using the fully automated two-dimensional chip gel electrophoresis system (Auto2D). This system was easy and convenient to use, and the resolution obtained was more sensitive and higher than that of conventional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). We separated and identified five isoforms of the 14-3-3 protein (beta/alpha, gamma, epsilon, zeta/delta, and eta) using the Auto2D system. We then examined the antioxidant effects of carnitine supplementation on the protein profiles of the cytosolic fraction in the aged rat hippocampus, demonstrating that carnitine supplementation suppressed the oxidation of methionine residues in these isoforms. Since methionine residues are easily oxidized to methionine sulfoxide, the convenient and high-resolution 2-D PAGE system can be available to analyze methionine oxidation avoiding artifactual oxidation. We showed here that the Auto2D system was a very useful tool for studying antioxidant effects through proteomic analysis of protein oxidation.

  9. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia

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    Giancarlo Balercia

    2014-12-01

    Full Text Available Objective: To evaluate the effectiveness of L-carnitine (LC or L-acetyl-carnitine (LAC or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s: Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 × 10 6 / mL, sperm forward motility < 50 %, and normal sperm morphology > 30 %; 59 patients completed the study.Intervention(s: Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s: Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s: Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s: The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71

  10. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia

    Directory of Open Access Journals (Sweden)

    Giancarlo Balercia

    2014-01-01

    Full Text Available Objective: To evaluate the effectiveness of L-carnitine (LC or L-acetyl-carnitine (LAC or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s: Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 × 10 6 / mL, sperm forward motility < 50 %, and normal sperm morphology > 30 %; 59 patients completed the study.Intervention(s: Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s: Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s: Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s: The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71

  11. 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

  12. L-carnitine intervention in energy metabolism of cancer cachexia patients%左卡尼汀干预癌性恶液质能量代谢

    Institute of Scientific and Technical Information of China (English)

    吴丹; 李苏宜

    2016-01-01

    Objective As cancer cachexia patients present low level of L-carnitine and abnormal energy metabolism, this study is to evaluate the impact of L-carnitine on energy metabolism of cancer cachexia patients. Methods We collected and analysed the results from the domestic and foreign published literature related to L-carnitine, cancer cachexia and energy metabolism in recent years. Results L-carnitine can ameliorate lipid metabolism disorders in cachexia patients, ameliorate anorexia by adjusting fatty acid metabolism in the hypothalamus;signiifcantly decrease activities of proteasome related with protein metabolism, inhibit proteolysis, improve performance status and fatigue of patients;improve insulin resistance and increase insulin sensitivity. Conclusions The intervention of L-carnitine in cancer cachexia is worth paying attention to, but still need large sample research evidence to conifrm, its underlying mechanisms also need further research.%目的癌性恶液质患者左旋肉碱水平低下,能量代谢异常,本文探讨左卡尼汀对癌性恶液质能量代谢的影响。方法回顾近年来国内外发表的有关左卡尼汀和癌性恶液质、能量代谢的中英文文献,并进行综合评述。结果左卡尼汀能够纠正恶液质患者脂质代谢紊乱,通过调节下丘脑脂肪酸代谢而改善恶液质者厌食;显著降低蛋白质代谢相关蛋白酶体活性,抑制蛋白质水解,改善患者一般情况,改善乏力;改善胰岛素抵抗,提高胰岛素敏感性。结论左卡尼汀干预癌性恶液质能量代谢值得关注,但尚需大样本研究证据证实,潜在机制也需要进一步深入研究。

  13. The effect of dietary supplementation with calcium salts of long chain fatty acids and/or L-carnitine on ovarian activity of Rahmani ewes.

    Science.gov (United States)

    El-Shahat, K H; Abo-El maaty, Amal M

    2010-01-01

    This study investigated the effect of dietary supplementation with calcium salts of long chain fatty acids with or without of l-carnitine on ovarian activity using 24 Rahmani ewes randomly allocated to four treatments. Control animals (n=6) were fed a basal diet of hay (64.2%) and barley grain (35.0%) plus minerals and vitamins (0.8%). Ewes on the three treatments received the same basal diet supplemented with calcium salts of long chain fatty acids (CSFA) at 3% of the basal diet dry matter intake (1.4 kg/ewe/d); 250 ppm l-carnitine (LC); or both these supplements (CSFA+LC). All use exhibited natural estrus on one or two occasions and were weighed at the start and the end of the study as well as body condition score was assessed at the end of study. All ewes were then synchronised for estrus using intravaginal sponges for 12 d prior to the start of the nutritional treatments and three weeks after the nutritional treatments began. The nutritional treatments were imposed for a total of 8 weeks. Blood samples were collected prior to the start of treatments and every two weeks thereafter except after sponge removal of first and second synchronisation where the blood samples were collected daily for progesterone assay. The results revealed that Rahmani ewes received basal diet (control) and l-carnitine had significantly decrease final body weight and body condition score (36.3+/-0.4; 36.8+/-0.3; 2.2+/-0.04; 2.1+/-0.05; pcarnitine (8.7+/-1.5) and CSFA+LC (8.0+/-0.6) treatments. The increased numbers occurred in the medium and large categories of follicles. In addition, the ovulation rates were significantly lower (pcarnitine (1.5+/-0.00) than for CSFA (2.5+/-0.3) and CSFA+LC (2.3+/-0.2). Furthermore, serum progesterone concentrations had risen and were significantly higher (pcarnitine (1.5+/-0.4 ng/ml). It was concluded that supplementation of the basal diet with l-carnitine alone did not improve performance of ewes or the ovarian response. However, the addition of

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

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    Saeed Mirzapor Sarab

    2016-08-01

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

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

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    Christianne de Faria Coelho

    2005-10-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

  17. Pro-Inflammatory and Oxidative Stress Pathways which Compromise Sperm Motility and Survival May Be Altered by L-Carnitine

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    Adel R. A. Abd-Allah

    2009-01-01

    Full Text Available The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s is poorly understood. Our objective is to help in understanding such mechanism(s to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS is used as a model of animal sepsis while L-carnitine (LCR is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group. The control group received Saline; the 2nd group was given LCR (500 mg/kg i.p, once. The third group was treated with LPS (5 mg/kg i.p once and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH, malondialdehyde (MDA and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage in testicular DNA. The pro-inflammatory mediator nitric oxide (NO in addition to lactate dehydrogenase (LDHx isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover

  18. 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.

  19. 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

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    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.

  20. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women.

    Science.gov (United States)

    Villani, R G; Gannon, J; Self, M; Rich, P A

    2000-06-01

    L-Carnitine (L-C) transports fatty acids into mitochondria for oxidation and is marketed as a weight loss supplement. In a double-blind investigation to test the weight loss efficacy of L-C, 36 moderately overweight premenopausal women were pair matched on Body Mass Index (BMI) and randomly assigned to two groups (N = 18). For 8 weeks the L-C group ingested 2 g twice daily of L-C, while the placebo (P) group ingested the same amount of lactose. All subjects walked for 30 min (60-70% maximum heart rate) 4 days/week. Body composition, resting energy expenditure (REE) and substrate utilization were estimated before and after treatment. For the subjects who completed the study (15 P, 13 L-C), no significant changes in mean total body mass (TBM), fat mass FM, and resting lipid utilization occurred over time, nor were there any significant differences between groups for any variable. Conversely REE increased significantly for all subjects, but no between group differences existed. Five of the L-C group experienced nausea or diarrhea and consequently did not complete the study. Eight weeks of L-C ingestion and walking did not significantly alter the TBM or FM of overweight women, thereby casting doubt on the efficacy of L-C supplementation for weight loss.

  1. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy

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    Anders A.F. Sima

    2014-01-01

    Full Text Available Objective — we evaluated frozen databases from two 52‑week randomized placebocontrolled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine (alc: 500 and 1,000 mg / day t. i. d.Research design and methods — intention-to-treat patients amounted to 1,257 or 93 % of enrolled patients. Efficacy end points were sural nerve morphometry, nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined.Results — data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg alc.Conclusions — these studies demonstrate that alc treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.

  2. Nutritional and Hormonal Regulation of Citrate and Carnitine/Acylcarnitine Transporters: Two Mitochondrial Carriers Involved in Fatty Acid Metabolism

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    Anna M. Giudetti

    2016-05-01

    Full Text Available The transport of solutes across the inner mitochondrial membrane is catalyzed by a family of nuclear-encoded membrane-embedded proteins called mitochondrial carriers (MCs. The citrate carrier (CiC and the carnitine/acylcarnitine transporter (CACT are two members of the MCs family involved in fatty acid metabolism. By conveying acetyl-coenzyme A, in the form of citrate, from the mitochondria to the cytosol, CiC contributes to fatty acid and cholesterol synthesis; CACT allows fatty acid oxidation, transporting cytosolic fatty acids, in the form of acylcarnitines, into the mitochondrial matrix. Fatty acid synthesis and oxidation are inversely regulated so that when fatty acid synthesis is activated, the catabolism of fatty acids is turned-off. Malonyl-CoA, produced by acetyl-coenzyme A carboxylase, a key enzyme of cytosolic fatty acid synthesis, represents a regulator of both metabolic pathways. CiC and CACT activity and expression are regulated by different nutritional and hormonal conditions. Defects in the corresponding genes have been directly linked to various human diseases. This review will assess the current understanding of CiC and CACT regulation; underlining their roles in physio-pathological conditions. Emphasis will be placed on the molecular basis of the regulation of CiC and CACT associated with fatty acid metabolism.

  3. Immunological responses in patients with tuberculosis and in vivo effects of acetyl-L-carnitine oral administration

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    Emilio Jirillo

    1993-01-01

    Full Text Available Tuberculosis (TBC is characterized by a complex immune response which parallels the clinical course of the disease. In this respect, acquired resistance, delayed hypersensitivity reaction and anergy are the main types of immune reactivity to mycobacterial antigens. In view of the presence of nonspecific and specific immune deficits in TBC patients, a clinical trial was carried out in a group of 20 individuals with active pulmonary TBC by oral administration of acetyl-L-carnitine (ALC. This drug, which has been shown to possess immunomodulating activities, was able to upregulate the T-dependent antibacterial activity in TBC patients after 30 days' treatment, while the same activity decreased in patients receiving placebo only. On the other hand, ALC did not modify serum levels of tumour necrosis factor-α, in the same individuals. This cytokine plays a detrimental rather than beneficial role in TBC pathogenesis. In the light of these data, ALC seems to be a powerful immunomodulator in the course of Mycobacterium tuberculosis infection and other mycobacteriosis.

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

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    Sridar Chittur

    2011-01-01

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

  5. The stimulation of ketogenesis by cannabinoids in cultured astrocytes defines carnitine palmitoyltransferase I as a new ceramide-activated enzyme.

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    Blázquez, C; Sánchez, C; Daza, A; Galve-Roperh, I; Guzmán, M

    1999-04-01

    The effects of cannabinoids on ketogenesis in primary cultures of rat astrocytes were studied. Delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, produced a malonyl-CoA-independent stimulation of carnitine palmitoyltransferase I (CPT-I) and ketogenesis from [14C]palmitate. The THC-induced stimulation of ketogenesis was mimicked by the synthetic cannabinoid HU-210 and was prevented by pertussis toxin and the CB1 cannabinoid receptor antagonist SR141716. Experiments performed with different cellular modulators indicated that the THC-induced stimulation of ketogenesis was independent of cyclic AMP, Ca2+, protein kinase C, and mitogen-activated protein kinase (MAPK). The possible involvement of ceramide in the activation of ketogenesis by cannabinoids was subsequently studied. THC produced a CB1 receptor-dependent stimulation of sphingomyelin breakdown that was concomitant to an elevation of intracellular ceramide levels. Addition of exogenous sphingomyelinase to the astrocyte culture medium led to a MAPK-independent activation of ketogenesis that was quantitatively similar and not additive to that exerted by THC. Furthermore, ceramide activated CPT-I in astrocyte mitochondria. Results thus indicate that cannabinoids stimulate ketogenesis in astrocytes by a mechanism that may rely on CB1 receptor activation, sphingomyelin hydrolysis, and ceramide-mediated activation of CPT-I.

  6. Comparison of the effects of aminoguanidine and L-carnitine treatments on somatosensorial evoked potentials in alloxan-diabetic rats.

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    Yildiz, O; Ozata, M; Ozkardeş, A; Deniz, G; Yildirimkaya, M; Corakçi, A; Yardim, M; Gündoğan, M A

    1996-10-01

    The effects of aminoguanidine (AG) and L-carnitine (LC) on somatosensorial evoked potential (SEP) latency and neural levels of thiobarbituric acid reactive substances (TBARS), products of lipid peroxidation, were compared in alloxan-diabetic rats. AG and LC were given to diabetic rats starting from the 3rd week after the induction of diabetes and lasting for 4 weeks. SEP latency was measured by stimulating via caudal nerve and recording via cortex, once weekly during the treatments. Diabetes caused deficits in SEP (P < 0.05 vs non-diabetic control rats, respectively). AG and LC restored SEP latencies slightly but not significantly, with the exception of the prominent effect of AG at the first week and both treatments at the 4th week of the treatments (P < 0.05 vs untreated diabetic rats, respectively). Diabetes caused elevation in neural TBARS levels (P < 0.05 vs non-diabetic group), which was prevented by both AG and LC (P < 0.05 vs untreated diabetic rats, respectively). Weight and the glucose levels were not influenced by the treatments. Our results suggest that AG improves SEP latencies better than LC. Our results also suggest that the beneficial effects of both AG and LC on diabetic neuropathy are not associated with the regulation of glycemia, but these effects may be related in part with prevention of lipid peroxidation.

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

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    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  8. Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene, OCTN2.

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    Xiaofei, E; Wada, Yasuhiko; Dakeishi, Miwako; Hirasawa, Fujiko; Murata, Katsuyuki; Masuda, Hirotake; Sugiyama, Toshihiro; Nikaido, Hiroko; Koizumi, Akio

    2002-07-01

    The purpose of this study was to test whether heterozygotes of juvenile visceral steatosis mice, a model for systemic carnitine deficiency, may develop age-associated cardiomyopathy. Tissue morphological observations were carried out by light and electron microscopy to compare the heterozygous and age-matched control mice at periods of 1 and 2 years. Possible effects of the pathological mutation on lipid and glucose levels was also evaluated in humans and mice. Except mild increases in serum cholesterol levels in male heterozygous mice and humans, no changes were found in other factors, indicating that none of the confounding factors seems to be profound. Results demonstrated that heterozygous mice had larger left ventriclular myocyte diameters than the control mice. Morphological changes in cardiac muscles by electron microscopy revealed age-associated changes of lipid deposition and abnormal mitochondria in heterozygous mice. Two out of 60 heterozygous cohort and one out of nine heterozygous trim-kill mice had cardiac hypertrophy at ages older than 2 years. The present study and our previous work suggest that the carrier state of OCTN2 pathological mutations might be a risk factor for age-associated cardiomyopathy.

  9. Species and muscle differences in L-carnitine levels in skeletal muscles based on a new simple assay.

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    Shimada, Kenichiro; Sakuma, Yoshinori; Wakamatsu, Junichi; Fukushima, Michihiro; Sekikawa, Mitsuo; Kuchida, Keigo; Mikami, Masayuki

    2004-11-01

    We have adapted the enzymatic method [Biochemical and Biophysical Research Communications 176 (3) (1991) 1617] for the safe and rapid assay of L-carnitine (L-CA) in skeletal muscle using a microplate reader. The concentration of L-CA in fresh semitendinosus muscle from broiler chicken, pig, beef cattle, deer, horse and goat muscle were 0.69, 1.09, 1.86-3.57, 4.57, 4.95 and 11.36 μmol/g wet weight, respectively. The animals which had higher concentration of L-CA, also had the highest amounts of myoglobin as an index to the redness of the muscle. Furthermore, we investigated this relationship between white muscle, M. pectoralis profundus, and red muscle, M. soleus, in laying hens. The L-CA and myoglobin concentration in red muscle were significantly higher than those in white muscle (p<0.01). These findings suggest that L-CA concentration in muscle is related to oxygen metabolism and to myofiber types.

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

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    Orem Ihsan

    2009-04-01

    Full Text Available Abstract Background Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects. Methods In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 ± 3.6 years participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL, in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP and mean values (MP of sprint power output and percent decrement of power (DEC were determined per bout and standardized relative to body masss. Heart rate (HR and blood lactate (LAC were measured prior to, during and following the five sprint bouts. Results Significant main effects (p Conclusion These findings indicate that short-term oral supplementation of GPLC can enhance peak power production in resistance trained males with significantly less LAC accumulation.

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

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    Panchamoorthy Rajasekar

    2007-01-01

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

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

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    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.

  13. Efficacy of L-carnitine supplementation on frailty statu