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European Journal of Nutrition

, Volume 52, Issue 5, pp 1421–1442 | Cite as

Mechanisms underlying the anti-wasting effect of l-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies

  • Robert Ringseis
  • Janine Keller
  • Klaus Eder
Review

Abstract

Purpose

Loss of skeletal muscle mass, also known as muscle wasting or muscle atrophy, is a common symptom of several chronic diseases, such as cancer and infectious diseases. Due to the strong negative impact of muscle loss on patient’s prognosis and quality of life, the development of efficacious treatment approaches to combat muscle wasting are of great importance. In order to evaluate the suitability of l-carnitine (LC) as an anti-wasting agent for clinical purposes the present review comprehensively summarizes the results from animal and clinical studies showing the effects of supplementation with LC or LC derivatives (acetyl-LC, propionyl-LC) on critical mechanisms involved in skeletal muscle loss under pathologic conditions, such as increased proteolysis, impaired protein synthesis, myonuclear apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction.

Results

Evidence from both animal and clinical studies exists that LC supplementation causes an improved nitrogen balance either due to increased protein synthesis or reduced protein degradation, an inhibition of apoptosis and an abrogation of inflammatory processes under pathologic conditions. Furthermore, strong evidence has been provided, at least from animal studies, that LC supplementation prevents oxidative stress and ameliorates mitochondrial function, whereas results from a very low number of available clinical studies in this regard are inconclusive.

Conclusion

In conclusion, LC supplementation beneficially influences several critical mechanisms involved in pathologic skeletal muscle loss that may at least partially explain the anti-catabolic effects and the improvement of fatigue-related parameters following LC supplementation in patients with chronic diseases. However, more suitable clinical trials (double-blinded, randomized, placebo-controlled, large-scale) are necessary in order to establish LC supplementation as strategy for anti-wasting therapy.

Keywords

l-carnitine Muscle wasting Cachexia Proteolysis Inflammation Oxidative stress 

Notes

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. 1.
    Moldawer LL, Sattler FR (1998) Human immunodeficiency virus-associated wasting and mechanisms of cachexia associated with inflammation. Semin Oncol 25:73–81Google Scholar
  2. 2.
    Lenk K, Schuler G, Adams V (2010) Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle 1:9–21CrossRefGoogle Scholar
  3. 3.
    Remels AH, Gosker HR, Langen RC, Schols AM (2012) The mechanisms of cachexia underlying muscle dysfunction in COPD. J Appl Physiol [Epub ahead of print]Google Scholar
  4. 4.
    Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker SD (2008) Cachexia: a new definition. Clin Nutr 27:793–799CrossRefGoogle Scholar
  5. 5.
    Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, Horton J, Johnson GJ, Moertel CG, Oken MM, Perlia C, Rosenbaum C, Silverstein MN, Skeel RT, Sponzo RW, Tormey DC (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 69:491–497CrossRefGoogle Scholar
  6. 6.
    Gramignano G, Lusso MR, Madeddu C, Massa E, Serpe R, Deiana L, Lamonica G, Dessì M, Spiga C, Astara G, Macciò A, Mantovani G (2006) Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition 22:136–145CrossRefGoogle Scholar
  7. 7.
    Smith KL, Tisdale MJ (1993) Increased protein degradation and decreased protein synthesis in skeletal muscle during cancer cachexia. Br J Cancer 67:680–685CrossRefGoogle Scholar
  8. 8.
    Tisdale MJ (2008) Catabolic mediators of cancer cachexia. Curr Opin Support Palliat Care 2:256–261CrossRefGoogle Scholar
  9. 9.
    Durham WJ, Dillon EL, Sheffield-Moore M (2009) Inflammatory burden and amino acid metabolism in cancer cachexia. Curr Opin Clin Nutr Metab Care 12:72–77CrossRefGoogle Scholar
  10. 10.
    Powers SK, Kavazis AN, McClung JM (2007) Oxidative stress and disuse muscle atrophy. J Appl Physiol 102:2389–2397CrossRefGoogle Scholar
  11. 11.
    Buck M, Chojkier M (1996) Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J 15:1753–1765Google Scholar
  12. 12.
    Li YP, Schwartz RJ, Waddell ID, Holloway BR, Reid MB (1998) Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-κB activation in response to tumor necrosis factor alpha. FASEB J 12:871–880Google Scholar
  13. 13.
    Pajak B, Orzechowska S, Pijet B, Pijet M, Pogorzelska A, Gajkowska B, Orzechowski A (2008) Crossroads of cytokine signaling–the chase to stop muscle cachexia. J Physiol Pharmacol 59:251–264Google Scholar
  14. 14.
    Eley HL, Tisdale MJ (2007) Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. J Biol Chem 282:7087–7097CrossRefGoogle Scholar
  15. 15.
    Roig E, Perez-Villa F, Morales M, Jiménez W, Orús J, Heras M, Sanz G (2000) Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 21:53–57CrossRefGoogle Scholar
  16. 16.
    Graziani G, Badalamenti S, Del Bo A, Marabini M, Gazzano G, Como G, Viganò E, Ambroso G, Morganti A (1993) Abnormal hemodynamics and elevated angiotensin II plasma levels in polydipsic patients on regular hemodialysis treatment. Kidney Int 44:107–114CrossRefGoogle Scholar
  17. 17.
    Brink M, Wellen J, Delafontaine P (1996) Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism. J Clin Invest 97:2509–2516CrossRefGoogle Scholar
  18. 18.
    Tabony AM, Yoshida T, Galvez S, Higashi Y, Sukhanov S, Chandrasekar B, Mitch WE, Delafontaine P (2011) Angiotensin II upregulates protein phosphatase 2Cα and inhibits AMP-activated protein kinase signaling and energy balance leading to skeletal muscle wasting. Hypertension 58:643–649CrossRefGoogle Scholar
  19. 19.
    Busquets S, Serpe R, Toledo M, Betancourt A, Marmonti E, Orpí M, Pin F, Capdevila E, Madeddu C, López-Soriano FJ, Mantovani G, Macciò A, Argilés JM (2012) l-Carnitine: an adequate supplement for a multi-targeted anti-wasting therapy in cancer. Clin Nutr 31:889–895CrossRefGoogle Scholar
  20. 20.
    Rebouche CJ, Seim H (1998) Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr 18:39–61CrossRefGoogle Scholar
  21. 21.
    Rebouche CJ (1992) Carnitine function and requirements during the life cycle. FASEB J 6:3379–3386Google Scholar
  22. 22.
    Vaz FM, Wanders RJ (2002) Carnitine biosynthesis in mammals. Biochem J 361:417–429CrossRefGoogle Scholar
  23. 23.
    Rebouche CJ, Lombard KA, Chenard CA (1993) Renal adaptation to dietary carnitine in humans. Am J Clin Nutr 58:660–665Google Scholar
  24. 24.
    Rebouche CJ (1983) Effect of dietary carnitine isomers and gamma-butyrobetaine on l-carnitine biosynthesis and metabolism in the rat. J Nutr 113:1906–1913Google Scholar
  25. 25.
    Olson AL, Rebouche CJ (1987) γ-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant. J Nutr 117:1024–1031Google Scholar
  26. 26.
    Brass EP (1995) Pharmacokinetic considerations for the therapeutic use of carnitine in hemodialysis patients. Clin Ther 17: 176–185, discussion 175Google Scholar
  27. 27.
    Hiatt WR, Regensteiner JG, Wolfel EE, Ruff L, Brass EP (1989) Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state. J Clin Invest 84:1167–1173CrossRefGoogle Scholar
  28. 28.
    Kerner J, Hoppel C (2000) Fatty acid import into mitochondria. Biochim Biophys Acta 1486:1–17CrossRefGoogle Scholar
  29. 29.
    Uziel G, Garavaglia B, Di Donato S (1988) Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated human skeletal muscle mitochondria. Muscle Nerve 11:720–724CrossRefGoogle Scholar
  30. 30.
    Ringseis R, Keller J, Eder K (2012) Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. Eur J Nutr 51:1–18CrossRefGoogle Scholar
  31. 31.
    Winter SC, Buist NR (2000) Cardiomyopathy in childhood, mitochondrial dysfunction, and the role of l-carnitine. Am Heart J 139:S63–S69CrossRefGoogle Scholar
  32. 32.
    Pons R, De Vivo DC (1995) Primary and secondary carnitine deficiency syndromes. J Child Neurol 10:S8–S24Google Scholar
  33. 33.
    Duranay M, Akay H, Yilmaz FM, Senes M, Tekeli N, Yücel D (2006) Effects of l-carnitine infusions on inflammatory and nutritional markers in haemodialysis patients. Nephrol Dial Transplant 21:3211–3214CrossRefGoogle Scholar
  34. 34.
    Steiber AL, Davis AT, Spry L, Strong J, Buss ML, Ratkiewicz MM, Weatherspoon LJ (2006) Carnitine treatment improved quality-of-life measure in a sample of Midwestern hemodialysis patients. JPEN J Parenter Enteral Nutr 30:10–15CrossRefGoogle Scholar
  35. 35.
    Biolo G, Stulle M, Bianco F, Mengozzi G, Barazzoni R, Vasile A, Panzetta G, Guarnieri G (2008) Insulin action on glucose and protein metabolism during l-carnitine supplementation in maintenance haemodialysis patients. Nephrol Dial Transplant 23:991–997CrossRefGoogle Scholar
  36. 36.
    Mantovani G, Macciò A, Madeddu C, Gramignano G, Serpe R, Massa E, Dessì M, Tanca FM, Sanna E, Deiana L, Panzone F, Contu P, Floris C (2008) Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. Nutrition 24:305–313CrossRefGoogle Scholar
  37. 37.
    Malaguarnera M, Vacante M, Bertino G, Neri S, Malaguarnera M, Gargante MP, Motta M, Lupo L, Chisari G, Bruno CM, Pennisi G, Bella R (2011) The supplementation of acetyl-l-carnitine decreases fatigue and increases quality of life in patients with hepatitis C treated with pegylated interferon-α 2b plus ribavirin. J Interferon Cytokine Res 31:653–659CrossRefGoogle Scholar
  38. 38.
    Malaguarnera M, Bella R, Vacante M, Giordano M, Malaguarnera G, Gargante MP, Motta M, Mistretta A, Rampello L, Pennisi G (2011) Acetyl-l-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy. Scand J Gastroenterol 46:750–759CrossRefGoogle Scholar
  39. 39.
    Malaguarnera M, Vacante M, Giordano M, Pennisi G, Bella R, Rampello L, Malaguarnera M, Li Volti G, Galvano F (2011) Oral acetyl-l-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 93:799–808CrossRefGoogle Scholar
  40. 40.
    Winter SC, Szabo-Aczel S, Curry CJ, Hutchinson HT, Hogue R, Shug A (1987) Plasma carnitine deficiency. Clinical observations in 51 pediatric patients. Am J Dis Child 141:660–665Google Scholar
  41. 41.
    Vinci E, Rampello E, Zanoli L, Oreste G, Pistone G, Malaguarnera M (2005) Serum carnitine levels in patients with tumoral cachexia. Eur J Intern Med 16:419–423CrossRefGoogle Scholar
  42. 42.
    Hockenberry MJ, Hooke MC, Gregurich M, McCarthy K (2009) Carnitine plasma levels and fatigue in children/adolescents receiving cisplatin, ifosfamide, or doxorubicin. J Pediatr Hematol Oncol 31:664–669CrossRefGoogle Scholar
  43. 43.
    De Simone C, Tzantzoglou S, Jirillo E, Marzo A, Vullo V, Martelli EA (1992) l-Carnitine deficiency in AIDS patients. AIDS 6:203–205CrossRefGoogle Scholar
  44. 44.
    Visarius TM, Stucki JW, Lauterburg BH (1999) Inhibition and stimulation of long-chain fatty acid oxidation by chloroacetaldehyde and methylene blue in rats. J Pharmacol Exp Ther 289:820–824Google Scholar
  45. 45.
    Lancaster CS, Hu C, Franke RM, Filipski KK, Orwick SJ, Chen Z, Zuo Z, Loos WJ, Sparreboom A (2010) Cisplatin-induced downregulation of OCTN2 affects carnitine wasting. Clin Cancer Res 16:4789–4799CrossRefGoogle Scholar
  46. 46.
    Lecker SH, Solomon V, Mitch WE, Goldberg AL (1999) Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr 129:S227–S237Google Scholar
  47. 47.
    Lecker SH, Solomon V, Price SR, Kwon YT, Mitch WE, Goldberg AL (1999) Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats. J Clin Invest 104:1411–1420CrossRefGoogle Scholar
  48. 48.
    Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83:731–801Google Scholar
  49. 49.
    Attaix D, Combaret L, Kee AJ (2003) Thaillandier D (2003) Mechanisms of ubiquitination and proteasome-dependent proteolysis in skeletal muscle. In: Zempleni J, Daniel H (eds) Molecular nutrition. CABI Publishing, Wallingford, pp 219–235CrossRefGoogle Scholar
  50. 50.
    Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, Price SR, Mitch WE, Goldberg AL (2004) Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 18:39–51CrossRefGoogle Scholar
  51. 51.
    Foletta VC, White LJ, Larsen AE, Léger B, Russell AP (2011) The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch 461:325–335CrossRefGoogle Scholar
  52. 52.
    Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708CrossRefGoogle Scholar
  53. 53.
    Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 98:14440–14445CrossRefGoogle Scholar
  54. 54.
    Lagirand-Cantaloube J, Offner N, Csibi A, Leibovitch MP, Batonnet-Pichon S, Tintignac LA, Segura CT, Leibovitch SA (2008) The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. EMBO J 27:1266–1276CrossRefGoogle Scholar
  55. 55.
    Lagirand-Cantaloube J, Cornille K, Csibi A, Batonnet-Pichon S, Leibovitch MP, Leibovitch SA (2009) Inhibition of atrogin-1/MAFbx mediated MyoD proteolysis prevents skeletal muscle atrophy in vivo. PLoS ONE 4:e4973CrossRefGoogle Scholar
  56. 56.
    Csibi A, Leibovitch MP, Cornille K, Tintignac LA, Leibovitch SA (2009) MAFbx/Atrogin-1 controls the activity of the initiation factor eIF3-f in skeletal muscle atrophy by targeting multiple C-terminal lysines. J Biol Chem 284:4413–4421CrossRefGoogle Scholar
  57. 57.
    Csibi A, Cornille K, Leibovitch MP et al (2010) The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse. PLoS ONE 5:e8994CrossRefGoogle Scholar
  58. 58.
    Schiaffino S, Mammucari C (2011) Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle 1:4CrossRefGoogle Scholar
  59. 59.
    Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96:857–868CrossRefGoogle Scholar
  60. 60.
    Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117:399–412CrossRefGoogle Scholar
  61. 61.
    Ringseis R, Keller J, Lukas I, Spielmann J, Most E, Couturier A, König B, Hirche F, Stangl GI, Wen G, Eder K (2012) Treatment with pharmacological PPARα agonists stimulates the ubiquitin proteasome pathway and myofibrillar protein breakdown in skeletal muscle of rodents. Biochim Biophys Acta 1830:2105–2117CrossRefGoogle Scholar
  62. 62.
    Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119:285–298CrossRefGoogle Scholar
  63. 63.
    Li YP, Chen Y, John J, Moylan J, Jin B, Mann DL, Reid MB (2005) TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J 19:362–370CrossRefGoogle Scholar
  64. 64.
    Langen RC, Haegens A, Vernooy JH, Wouters EF, de Winther MP, Carlsen H, Steele C, Shoelson SE, Schols AM (2012) NF-κB activation is required for the transition of pulmonary inflammation to muscle atrophy. Am J Respir Cell Mol Biol 47:288–297CrossRefGoogle Scholar
  65. 65.
    Morley JE, Thomas DR, Wilson MM (2006) Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 83:735–743Google Scholar
  66. 66.
    Sandri M (2008) Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda) 23:160–170CrossRefGoogle Scholar
  67. 67.
    Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37:1974–1984CrossRefGoogle Scholar
  68. 68.
    van Royen M, Carbó N, Busquets S, Alvarez B, Quinn LS, López-Soriano FJ, Argilés JM (2000) DNA fragmentation occurs in skeletal muscle during tumor growth: a link with cancer cachexia? Biochem Biophys Res Commun 270:533–537CrossRefGoogle Scholar
  69. 69.
    Busquets S, Deans C, Figueras M, Moore-Carrasco R, López-Soriano FJ, Fearon KC, Argilés JM (2007) Apoptosis is present in skeletal muscle of cachectic gastro-intestinal cancer patients. Clin Nutr 26:614–618CrossRefGoogle Scholar
  70. 70.
    Agustí AG, Sauleda J, Miralles C, Gomez C, Togores B, Sala E, Batle S, Busquets X (2002) Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 166:485–489CrossRefGoogle Scholar
  71. 71.
    Dupont-Versteegden EE, Strotman BA, Gurley CM, Gaddy D, Knox M, Fluckey JD, Peterson CA (2006) Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei. Am J Physiol Regul Integr Comp Physiol 291:1730–1740CrossRefGoogle Scholar
  72. 72.
    Dupont-Versteegden EE (2006) Apoptosis in skeletal muscle and its relevance to atrophy. World J Gastroenterol 12:7463–7466Google Scholar
  73. 73.
    Primeau AJ, Adhihetty PJ, Hood DA (2002) Apoptosis in heart and skeletal muscle. Can J Appl Physiol 27:349–395CrossRefGoogle Scholar
  74. 74.
    Argilés JM, López-Soriano FJ, Busquets S (2008) Apoptosis signalling is essential and precedes protein degradation in wasting skeletal muscle during catabolic conditions. Int J Biochem Cell Biol 40:1674–1678CrossRefGoogle Scholar
  75. 75.
    Argilés JM, Busquets S, Toledo M, López-Soriano FJ (2009) The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care 3:263–268CrossRefGoogle Scholar
  76. 76.
    Adams V, Linke A, Wisloff U, Döring C, Erbs S, Kränkel N, Witt CC, Labeit S, Müller-Werdan U, Schuler G, Hambrecht R (2007) Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: effect on myocardial contractility. Cardiovasc Res 73:120–129CrossRefGoogle Scholar
  77. 77.
    Wyke SM, Tisdale MJ (2005) NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle. Br J Cancer 92:711–721CrossRefGoogle Scholar
  78. 78.
    Olson EN, Klein WH (1994) bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out. Genes Dev 8:1–8CrossRefGoogle Scholar
  79. 79.
    Adams V, Nehrhoff B, Späte U, Linke A, Schulze PC, Baur A, Gielen S, Hambrecht R, Schuler G (2002) Induction of iNOS expression in skeletal muscle by IL-1beta and NF-κB activation: an in vitro and in vivo study. Cardiovasc Res 54:95–104CrossRefGoogle Scholar
  80. 80.
    Brown GC (2001) Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 1504:46–57CrossRefGoogle Scholar
  81. 81.
    Van Helvoort HA, Heijdra YF, Thijs HM, Viña J, Wanten GJ, Dekhuijzen PN (2006) Exercise-induced systemic effects in muscle-wasted patients with COPD. Med Sci Sports Exerc 38:1543–1552CrossRefGoogle Scholar
  82. 82.
    Li YP, Chen Y, Li AS, Reid MB (2003) Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Physiol Cell Physiol 285:C806–C812CrossRefGoogle Scholar
  83. 83.
    White JP, Baltgalvis KA, Puppa MJ, Sato S, Baynes JW, Carson JA (2011) Muscle oxidative capacity during IL-6-dependent cancer cachexia. Am J Physiol Regul Integr Comp Physiol 300:201–211CrossRefGoogle Scholar
  84. 84.
    Constantinou C, Fontes de Oliveira CC, Mintzopoulos D, Busquets S, He J, Kesarwani M, Mindrinos M, Rahme LG, Argilés JM, Tzika AA (2011) Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine model of cancer cachexia. Int J Mol Med 27:15–24Google Scholar
  85. 85.
    Padfield KE, Astrakas LG, Zhang Q, Gopalan S, Dai G, Mindrinos MN, Tompkins RG, Rahme LG, Tzika AA (2005) Burn injury causes mitochondrial dysfunction in skeletal muscle. Proc Natl Acad Sci U S A 102:5368–5373CrossRefGoogle Scholar
  86. 86.
    Tzika AA, Mintzopoulos D, Padfield K, Wilhelmy J, Mindrinos MN, Yu H, Cao H, Zhang Q, Astrakas LG, Zhang J, Yu YM, Rahme LG, Tompkins RG (2008) Reduced rate of adenosine triphosphate synthesis by in vivo 31P nuclear magnetic resonance spectroscopy and downregulation of PGC-1beta in distal skeletal muscle following burn. Int J Mol Med 221:201–208Google Scholar
  87. 87.
    Vescovo G, Ravara B, Gobbo V, Sandri M, Angelini A, Della Barbera M, Dona M, Peluso G, Calvani M, Mosconi L, Dalla Libera L (2002) l-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure. Am J Physiol Cell Physiol 283:802–810CrossRefGoogle Scholar
  88. 88.
    Keller J, Ringseis R, Koc A, Lukas I, Kluge H, Eder K (2012) Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets. Animal 6:70–78CrossRefGoogle Scholar
  89. 89.
    Doberenz J, Birkenfeld C, Kluge H, Eder K (2006) Effects of l-carnitine supplementation in pregnant sows on plasma concentrations of insulin-like growth factors, various hormones and metabolites and chorion characteristics. J Anim Physiol Anim Nutr (Berl) 90:487–499CrossRefGoogle Scholar
  90. 90.
    Woodworth JC, Tokach MD, Nelssen JL, Goodband RD, Dritz SS et al (2007) Influence of dietary l-carnitine and chromium picolinate on blood hormones and metabolites of gestating sows fed one meal per day. J Anim Sci 85:2524–2537CrossRefGoogle Scholar
  91. 91.
    Brown KR, Goodband RD, Tokach MD, Dritz SS, Nelssen JL et al (2008) Effects of feeding l-carnitine to gilts through day 70 of gestation on litter traits and the expression of insulin-like growth factor system components and l-carnitine concentration in foetal tissues. J Anim Physiol Anim Nutr (Berl) 92:660–667CrossRefGoogle Scholar
  92. 92.
    Keller J, Ringseis R, Priebe S, Guthke R, Kluge H et al (2011) Dietary l-carnitine alters gene expression in skeletal muscle of piglets. Mol Nutr Food Res 55:419–429CrossRefGoogle Scholar
  93. 93.
    Ahmad S, Robertson HT, Golper TA, Wolfson M, Kurtin P, Katz LA, Hirschberg R, Nicora R, Ashbrook DW, Kopple JD (1990) Multicenter trial of l-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects. Kidney Int 38:912–918CrossRefGoogle Scholar
  94. 94.
    Heller W, Musil HE, Gaebel G, Hempel V, Krug W, Köhn HJ (1986) Effect of l-carnitine on post-stress metabolism in surgical patients. Infusionsther Klin Ernahr 13:268–276Google Scholar
  95. 95.
    Rössle C, Pichard C, Roulet M, Chiolero R, Schutz Y, Temler E, Schindler C, Zurlo F, Jéquier E, Fürst P (1988) Effect of l-carnitine supplemented total parenteral nutrition on postoperative lipid and nitrogen utilization. Klin Wochenschr 66:1202–1211CrossRefGoogle Scholar
  96. 96.
    Pichard C, Roulet M, Schutz Y, Rössle C, Chiolero R, Temler E, Schindler C, Zurlo F, Fürst P, Jéquier E (1989) 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. Am J Clin Nutr 49:283–289Google Scholar
  97. 97.
    Roulet M, Pichard C, Rössle C, Bretenstein E, Schutz Y, Chiolero R, Fürst P, Jéquier E (1989) Adverse effects of high dose carnitine supplementation of total parenteral nutrition on protein and fat oxidation in the critically ill. Clin Nutr 8:83–87CrossRefGoogle Scholar
  98. 98.
    Tao RC, Peck GK, Yoshimura NN (1981) Effect of carnitine on liver fat and nitrogen balance in intravenously fed growing rats. J Nutr 111:171–177Google Scholar
  99. 99.
    Vazquez JA, Paul HS, Adibi SA (1988) Intravenously infused carnitine: influence on protein and branched-chain amino acid metabolism in starved and parenterally fed rats. Am J Clin Nutr 48:570–574Google Scholar
  100. 100.
    Bohles H, Segerer H, Fekl W (1984) Improved N-retention during l-carnitine-supplemented total parenteral nutrition. JPEN J Parenter Enteral Nutr 8:9–13CrossRefGoogle Scholar
  101. 101.
    Cassano P, Flück M, Giovanna Sciancalepore A, Pesce V, Calvani M, Hoppeler H, Cantatore P, Gadaleta MN (2010) Muscle unloading potentiates the effects of acetyl-l-carnitine on the slow oxidative muscle phenotype. BioFactors 36:70–77Google Scholar
  102. 102.
    Moriggi M, Cassano P, Vasso M, Capitanio D, Fania C, Musicco C, Pesce V, Gadaleta MN, Gelfi C (2008) A DIGE approach for the assessment of rat soleus muscle changes during unloading: effect of acetyl-l-carnitine supplementation. Proteomics 8:3588–3604CrossRefGoogle Scholar
  103. 103.
    Heo K, Odle J, Han IK, Cho W, Seo S, van Heugten E, Pilkington DH (2000) Dietary l-carnitine improves nitrogen utilization in growing pigs fed low energy, fat-containing diets. J Nutr 130:1809–1814Google Scholar
  104. 104.
    Greenwood RH, Titgemeyer EC, Stokka GL, Drouillard JS, Löest CA (2001) Effects of l-carnitine on nitrogen retention and blood metabolites of growing steers and performance of finishing steers. J Anim Sci 79:254–260Google Scholar
  105. 105.
    Musser RE, Goodband RD, Tokach MD, Owen KQ, Nelssen JL, Blum SA, Campbell RG, Smits R, Dritz SS, Civis CA (1999) Effects of l-carnitine fed during lactation on sow and litter performance. J Anim Sci 77:3289–3295Google Scholar
  106. 106.
    Kita K, Kato S, Amanyaman M, Okumura J, Yokota H (2002) Dietary l-carnitine increases plasma insulin-like growth factor-I concentration in chicks fed a diet with adequate dietary protein level. Br Poult Sci 43:117–121CrossRefGoogle Scholar
  107. 107.
    Heo YR, Kang CW, Cha YS (2001) l-Carnitine changes the levels of insulin-like growth factors (IGFs) and IGF binding proteins in streptozotocin-induced diabetic rat. J Nutr Sci Vitaminol (Tokyo) 47:329–334CrossRefGoogle Scholar
  108. 108.
    Di Marzio L, Moretti S, D’Alò S, Zazzeroni F, Marcellini S, Smacchia C, Alesse E, Cifone MG, De Simone C (1999) Acetyl-l-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Clin Immunol 92:103–110CrossRefGoogle Scholar
  109. 109.
    Beshlawy AE, Abd El Dayem SM, Mougy FE, Gafar EA, Samir H (2010) Screening of growth hormone deficiency in short thalassaemic patients and effect of l-carnitine treatment. Arch Med Sci 6:90–95CrossRefGoogle Scholar
  110. 110.
    Galloway SD, Craig TP, Cleland SJ (2011) Effects of oral: l-carnitine supplementation on insulin sensitivity indices in response to glucose feeding in lean and overweight/obese males. Amino Acids 41:507–515CrossRefGoogle Scholar
  111. 111.
    Bellinghieri G, Savica V, Mallamace A, Di Stefano C, Consolo F, Spagnoli LG, Villaschi S, Palmieri G, Corsi M, Maccari F (1983) Correlation between increased serum and tissue l-carnitine levels and improved muscle symptoms in hemodialyzed patients. Am J Clin Nutr 38:523–531Google Scholar
  112. 112.
    Fagher B, Cederblad G, Eriksson M, Monti M, Moritz U, Nilsson-Ehle P, Thysell H (1985) l-Carnitine and haemodialysis: double blind study on muscle function and metabolism and peripheral nerve function. Scand J Clin Lab Invest 45:169–178CrossRefGoogle Scholar
  113. 113.
    Vaux EC, Taylor DJ, Altmann P, Rajagopalan B, Graham K, Cooper R, Bonomo Y, Styles P (2004) Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease. Nephron Clin Pract 97:41–48CrossRefGoogle Scholar
  114. 114.
    Spagnoli LG, Palmieri G, Mauriello A, Vacha GM, D’Iddio S, Giorcelli G, Corsi M (1990) Morphometric evidence of the trophic effect of l-carnitine on human skeletal muscle. Nephron 55:16–23CrossRefGoogle Scholar
  115. 115.
    Giovenali P, Fenocchio D, Montanari G, Cancellotti C, D’Iddio S, Buoncristiani U, Pelagaggia M, Ribacchi R (1994) Selective trophic effect of l-carnitine in type I and IIa skeletal muscle fibers. Kidney Int 46:1616–1619CrossRefGoogle Scholar
  116. 116.
    Pastorino JG, Snyder JW, Serroni A, Hoek JB, Farber JL (1993) Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J Biol Chem 268:13791–13798Google Scholar
  117. 117.
    Sener G, Ekşioğlu-Demiralp E, Cetiner M, Ercan F, Sirvanci S, Gedik N, Yeğen BC (2006) l-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell Biol Toxicol 22:47–60CrossRefGoogle Scholar
  118. 118.
    Therrien G, Rose C, Butterworth J, Butterworth RF (1997) Protective effect of l-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat. Hepatology 25:551–556CrossRefGoogle Scholar
  119. 119.
    Galli G, Fratelli M (1993) Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: inhibition by l-acetylcarnitine. Exp Cell Res 204:54–60CrossRefGoogle Scholar
  120. 120.
    Revoltella RP, Dal Canto B, Caracciolo L, D’Urso CM (1994) l-Carnitine and some of its analogs delay the onset of apoptotic cell death initiated in murine C2.8 hepatocytic cells after hepatocyte growth factor deprivation. Biochim Biophys Acta 1224:333–341CrossRefGoogle Scholar
  121. 121.
    Di Marzio L, Alesse E, Roncaioli P, Muzi P, Moretti S, Marcellini S, Amicosante G, De Simone C, Cifone MG (1997) Influence of l-carnitine on CD95 cross-lining-induced apoptosis and ceramide generation in human cell lines: correlation with its effects on purified acidic and neutral sphingomyelinases in vitro. Proc Assoc Am Physicians 109:154–163Google Scholar
  122. 122.
    Kira Y, Nishikawa M, Ochi A, Sato E, Inoue M (2006) l-Carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis. Brain Res 1070:206–214CrossRefGoogle Scholar
  123. 123.
    Tamilselvan J, Jayaraman G, Sivarajan K, Panneerselvam C (2007) Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic acid. Free Radic Biol Med 43:1656–1669CrossRefGoogle Scholar
  124. 124.
    Andrieu-Abadie N, Jaffrezou JP, Hatem S, Laurent G, Levade T, Mercadier JJ (1999) l-Carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation. FASEB J 13:1501–1510Google Scholar
  125. 125.
    Oyanagi E, Yano H, Uchida M, Utsumi K, Sasaki J (2011) Protective action of l-carnitine on cardiac mitochondrial function and structure against fatty acid stress. Biochem Biophys Res Commun 412:61–67CrossRefGoogle Scholar
  126. 126.
    Chao HH, Liu JC, Hong HJ, Lin JW, Chen CH, Cheng TH (2011) l-Carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes. Int J Cardiol 146:145–152CrossRefGoogle Scholar
  127. 127.
    Cui J, Das DK, Bertelli A, Tosaki A (2003) Effects of l-carnitine and its derivatives on postischemic cardiac function, ventricular fibrillation and necrotic and apoptotic cardiomyocyte death in isolated rat hearts. Mol Cell Biochem 254:227–234CrossRefGoogle Scholar
  128. 128.
    Cifone MG, Alesse E, Di Marzio L, Ruggeri B, Zazzeroni F, Moretti S, Famularo G, Steinberg SM, Vullo E, De Simone C (1997) Effect of l-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from AIDS patients. Proc Assoc Am Physicians 109:146–153Google Scholar
  129. 129.
    Cossarizza A, Mussini C, Mongiardo N, Borghi V, Sabbatini A, De Rienzo B, Franceschi C (1997) Mitochondria alterations and dramatic tendency to undergo apoptosis in peripheral blood lymphocytes during acute HIV syndrome. AIDS 11:19–26CrossRefGoogle Scholar
  130. 130.
    Moretti S, Alesse E, Di Marzio L, Zazzeroni F, Ruggeri B, Marcellini S, Famularo G, Steinberg SM, Boschini A, Cifone MG, De Simone C (1998) Effect of l-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood 91:3817–3824Google Scholar
  131. 131.
    Moretti S, Famularo G, Marcellini S, Boschini A, Santini G, Trinchieri V, Lucci L, Alesse E, De Simone C (2002) l-Carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine. Antioxid Redox Signal 4:391–403CrossRefGoogle Scholar
  132. 132.
    Rodriguez-Tarduchy G, Collins MK, García I, López-Rivas A (1992) Insulin-like growth factor-I inhibits apoptosis in IL-3-dependent hemopoietic cells. J Immunol 149:535–540Google Scholar
  133. 133.
    De Simone C, Tzantzoglou S, Famularo G, Moretti S, Paoletti F, Vullo V, Delia S (1993) High dose l-carnitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacol Immunotoxicol 15:1–12CrossRefGoogle Scholar
  134. 134.
    De Simone C, Famularo G, Tzantzoglou S, Trinchieri V, Moretti S, Sorice F (1994) Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral l-carnitine. AIDS 8:655–660CrossRefGoogle Scholar
  135. 135.
    Miguel-Carrasco JL, Mate A, Monserrat MT, Arias JL, Aramburu O, Vázquez CM (2008) The role of inflammatory markers in the cardioprotective effect of l-carnitine in l-NAME-induced hypertension. Am J Hypertens 21:1231–1237CrossRefGoogle Scholar
  136. 136.
    Winter BK, Fiskum G, Gallo LL (1995) Effects of l-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. Br J Cancer 72:1173–1179CrossRefGoogle Scholar
  137. 137.
    Idrovo JP, Yang WL, Matsuda A, Nicastro J, Coppa GF, Wang P (2012) Post-treatment with the combination of 5-aminoimidazole-4-carboxyamide ribonucleoside and carnitine improves renal function after ischemia/reperfusion injury. Shock 37:39–46CrossRefGoogle Scholar
  138. 138.
    Laviano A, Molfino A, Seelaender M, Frascaria T, Bertini G, Ramaccini C, Bollea MR, Citro G, Rossi Fanelli F (2011) Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats. Cancer Invest 29:696–700CrossRefGoogle Scholar
  139. 139.
    Liu S, Wu HJ, Zhang ZQ, Chen Q, Liu B, Wu JP, Zhu L (2011) l-Carnitine ameliorates cancer cachexia in mice by regulating the expression and activity of carnitine palmityl transferase. Cancer Biol Ther 12:125–130CrossRefGoogle Scholar
  140. 140.
    Malaguarnera M, Gargante MP, Russo C, Antic T, Vacante M, Malaguarnera M, Avitabile T, Li Volti G, Galvano F (2010) l-Carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis—a randomized and controlled clinical trial. Am J Gastroenterol 105:1338–1345CrossRefGoogle Scholar
  141. 141.
    Delogu G, De Simone C, Famularo G, Fegiz A, Paoletti F, Jirillo E (1993) Anaesthetics modulate tumour necrosis factor alpha: effects of l-carnitine supplementation in surgical patients. Preliminary results. Mediators Inflamm 2:33–36CrossRefGoogle Scholar
  142. 142.
    Savica V, Santoro D, Mazzaglia G, Ciolino F, Monardo P, Calvani M, Bellinghieri G, Kopple JD (2005) l-Carnitine infusions may suppress serum C-reactive protein and improve nutritional status in maintenance hemodialysis patients. J Ren Nutr 15:225–230CrossRefGoogle Scholar
  143. 143.
    Shakeri A, Tabibi H, Hedayati M (2010) Effects of l-carnitine supplement on serum inflammatory cytokines, C-reactive protein, lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia. Hemodial Int 14:498–504CrossRefGoogle Scholar
  144. 144.
    Suchitra MM, Ashalatha VL, Sailaja E, Rao AM, Reddy VS, Bitla AR, Sivakumar V, Rao PV (2011) The effect of l-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl 22:1155–1159Google Scholar
  145. 145.
    Derosa G, Maffioli P, Ferrari I, D’Angelo A, Fogari E, Palumbo I, Randazzo S, Cicero AF (2010) Orlistat and l-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Endocr J 57:777–786CrossRefGoogle Scholar
  146. 146.
    Kumar A, Singh RB, Saxena M, Niaz MA, Josh SR, Chattopadhyay P, Mechirova V, Pella D, Fedacko J (2007) Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study. Acta Cardiol 62:349–354CrossRefGoogle Scholar
  147. 147.
    Dutta A, Ray K, Singh VK, Vats P, Singh SN, Singh SB (2008) l-Carnitine supplementation attenuates intermittent hypoxia-induced oxidative stress and delays muscle fatigue in rats. Exp Physiol 93:1139–1146CrossRefGoogle Scholar
  148. 148.
    Rajasekar P, Anuradha CV (2007) l-Carnitine inhibits protein glycation in vitro and in vivo: evidence for a role in diabetic management. Acta Diabetol 44:83–90CrossRefGoogle Scholar
  149. 149.
    Breitkreutz R, Babylon A, Hack V, Schuster K, Tokus M, Böhles H, Hagmüller E, Edler L, Holm E, Dröge W (2000) Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases. Br J Cancer 82:399–403CrossRefGoogle Scholar
  150. 150.
    Al-Majed AA, Sayed-Ahmed MM, Al-Yahya AA, Aleisa AM, Al-Rejaie SS, Al-Shabanah OA (2006) Propionyl-l-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Pharmacol Res 53:278–286CrossRefGoogle Scholar
  151. 151.
    Alvarez M, Malécot CO, Gannier F, Lignon JM (2005) Antimony-induced cardiomyopathy in guinea-pig and protection by l-carnitine. Br J Pharmacol 144:17–27CrossRefGoogle Scholar
  152. 152.
    Annadurai T, Vigneshwari S, Thirukumaran R, Thomas PA, Geraldine P (2011) Acetyl-l-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats. J Physiol Biochem 67:519–530CrossRefGoogle Scholar
  153. 153.
    Sayed-Ahmed MM (2011) l-Carnitine attenuates ifosfamide-induced carnitine deficiency and decreased intramitochondrial CoA-SH in rat kidney tissues. J Nephrol 24:490–498CrossRefGoogle Scholar
  154. 154.
    Mescka C, Moraes T, Rosa A, Mazzola P, Piccoli B, Jacques C, Dalazen G, Coelho J, Cortes M, Terra M, Regla Vargas C, Dutra-Filho CS (2011) In vivo neuroprotective effect of l-carnitine against oxidative stress in maple syrup urine disease. Metab Brain Dis 26:21–28CrossRefGoogle Scholar
  155. 155.
    Türker Y, Nazıroğlu M, Gümral N, Celik O, Saygın M, Cömlekçi S, Flores-Arce M (2011) Selenium and l-carnitine reduce oxidative stress in the heart of rat induced by 2.45 GHz radiation from wireless devices. Biol Trace Elem Res 143:1640–1650CrossRefGoogle Scholar
  156. 156.
    Naziroğlu M, Gümral N (2009) Modulator effects of l-carnitine and selenium on wireless devices (2.45 GHz)-induced oxidative stress and electroencephalography records in brain of rat. Int J Radiat Biol 85:680–689CrossRefGoogle Scholar
  157. 157.
    Gumral N, Naziroglu M, Koyu A, Ongel K, Celik O, Saygin M, Kahriman M, Caliskan S, Kayan M, Gencel O, Flores-Arce MF (2009) Effects of selenium and l-carnitine on oxidative stress in blood of rat induced by 2.45 GHz radiation from wireless devices. Biol Trace Elem Res 132:153–163CrossRefGoogle Scholar
  158. 158.
    Alshabanah OA, Hafez MM, Al-Harbi MM, Hassan ZK, Al Rejaie SS, Asiri YA, Sayed-Ahmed MM (2010) Doxorubicin toxicity can be ameliorated during antioxidant l-carnitine supplementation. Oxid Med Cell Longev 3:428–433CrossRefGoogle Scholar
  159. 159.
    Moosavi SM, Ashtiyani SC, Hosseinkhani S, Shirazi M (2010) Comparison of the effects of l-carnitine and α-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats. Urol Res 38:187–194CrossRefGoogle Scholar
  160. 160.
    Moosavi SM, Ashtiyani SC, Hosseinkhani S (2011) l-Carnitine improves oxidative stress and suppressed energy metabolism but not renal dysfunction following release of acute unilateral ureteral obstruction in rat. Neurourol Urodyn 30:480–487CrossRefGoogle Scholar
  161. 161.
    Aleisa AM, Al-Majed AA, Al-Yahya AA, Al-Rejaie SS, Bakheet SA, Al-Shabanah OA, Sayed-Ahmed MM (2007) Reversal of cisplatin-induced carnitine deficiency and energy starvation by propionyl-l-carnitine in rat kidney tissues. Clin Exp Pharmacol Physiol 34:1252–1259CrossRefGoogle Scholar
  162. 162.
    Tastekin N, Aydogdu N, Dokmeci D, Usta U, Birtane M, Erbas H, Ture M (2007) Protective effects of l-carnitine and alpha-lipoic acid in rats with adjuvant arthritis. Pharmacol Res 56:303–310CrossRefGoogle Scholar
  163. 163.
    Yapar K, Kart A, Karapehlivan M, Atakisi O, Tunca R, Erginsoy S, Citil M (2007) Hepatoprotective effect of l-carnitine against acute acetaminophen toxicity in mice. Exp Toxicol Pathol 59:121–128CrossRefGoogle Scholar
  164. 164.
    Augustyniak A, Skrzydlewska E (2009) l-Carnitine in the lipid and protein protection against ethanol-induced oxidative stress. Alcohol 43:217–223CrossRefGoogle Scholar
  165. 165.
    Augustyniak A, Skrzydlewska E (2010) The influence of l-carnitine supplementation on the antioxidative abilities of serum and the central nervous system of ethanol-induced rats. Metab Brain Dis 25:381–389CrossRefGoogle Scholar
  166. 166.
    Silva-Adaya D, Pérez-De La Cruz V, Herrera-Mundo MN, Mendoza-Macedo K, Villeda-Hernández J, Binienda Z, Ali SF, Santamaría A (2008) Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of l-carnitine. J Neurochem 105:677–689CrossRefGoogle Scholar
  167. 167.
    Mate A, Miguel-Carrasco JL, Vázquez CM (2010) The therapeutic prospects of using l-carnitine to manage hypertension-related organ damage. Drug Discov Today 15:484–492CrossRefGoogle Scholar
  168. 168.
    Miguel-Carrasco JL, Monserrat MT, Mate A, Vázquez CM (2010) Comparative effects of captopril and l-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats. Eur J Pharmacol 632:65–72CrossRefGoogle Scholar
  169. 169.
    Shaker ME, Houssen ME, Abo-Hashem EM, Ibrahim TM (2009) Comparison of vitamin E, l-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress. J Physiol Biochem 65:225–233CrossRefGoogle Scholar
  170. 170.
    Fatouros IG, Douroudos I, Panagoutsos S, Pasadakis P, Nikolaidis MG, Chatzinikolaou A, Sovatzidis A, Michailidis Y, Jamurtas AZ, Mandalidis D, Taxildaris K, Vargemezis V (2010) Effects of l-carnitine on oxidative stress responses in patients with renal disease. Med Sci Sports Exerc 42:1809–1818CrossRefGoogle Scholar
  171. 171.
    Malaguarnera M, Vacante M, Avitabile T, Malaguarnera M, Cammalleri L, Motta M (2009) l-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin Nutr 89:71–76CrossRefGoogle Scholar
  172. 172.
    Pignatelli P, Tellan G, Marandola M, Carnevale R, Loffredo L, Schillizzi M, Proietti M, Violi F, Chirletti P, Delogu G (2011) Effect of l-carnitine on oxidative stress and platelet activation after major surgery. Acta Anaesthesiol Scand 55:1022–1028Google Scholar
  173. 173.
    Paradies G, Ruggiero FM, Gadaleta MN, Quagliariello E (1992) The effect of aging and acetyl-l-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. Biochim Biophys Acta 1103:324–326CrossRefGoogle Scholar
  174. 174.
    Gadaleta MN, Petruzzella V, Renis M, Fracasso F, Cantatore P (1990) Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of l-carnitine. Eur J Biochem 187:501–506CrossRefGoogle Scholar
  175. 175.
    Dowson JH, Wilton-Cox H, Cairns MR, Ramacci MT (1992) The morphology of lipopigment in rat Purkinje neurons after chronic acetyl-l-carnitine administration: a reduction in aging-related changes. Biol Psychiatry 32:179–187CrossRefGoogle Scholar
  176. 176.
    Amenta F, Ferrante F, Lucreziotti R, Ricci A, Ramacci MT (1989) Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-l-carnitine treatment. Arch Gerontol Geriatr 9:147–153CrossRefGoogle Scholar
  177. 177.
    Ghirardi O, Caprioli A, Milano S, Giuliani A, Ramacci MT, Angelucci L (1992) Active avoidance learning in old rats chronically treated with levocarnitine acetyl. Physiol Behav 52:185–187CrossRefGoogle Scholar
  178. 178.
    Aureli T, Miccheli A, Ricciolini R, Di Cocco ME, Ramacci MT, Angelucci L, Ghirardi O, Conti F (1990) Aging brain: effect of acetyl-l-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy. Brain Res 526:108–112CrossRefGoogle Scholar
  179. 179.
    Rabchevsky AG, Patel SP, Springer JE (2011) Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward? Pharmacol Ther 132:15–29CrossRefGoogle Scholar
  180. 180.
    Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE (1997) Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res 765:283–290CrossRefGoogle Scholar
  181. 181.
    Sullivan PG, Krishnamurthy S, Patel SP, Pandya JD, Rabchevsky AG (2007) Temporal characterization of mitochondrial bioenergetics after spinal cord injury. J Neurotrauma 24:991–999CrossRefGoogle Scholar
  182. 182.
    Patel BP, Hamadeh MJ (2009) Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis. Clin Nutr 28:604–617CrossRefGoogle Scholar
  183. 183.
    McEwen ML, Sullivan PG, Springer JE (2007) Pretreatment with the cyclosporin derivative, NIM811, improves the function of synaptic mitochondria following spinal cord contusion in rats. J Neurotrauma 24:613–624CrossRefGoogle Scholar
  184. 184.
    Patel SP, Sullivan PG, Lyttle TS, Rabchevsky AG (2010) Acetyl-l-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury. J Neurochem 114:291–301Google Scholar
  185. 185.
    Patel SP, Sullivan PG, Lyttle TS, Magnuson DS, Rabchevsky AG (2012) Acetyl-l-carnitine treatment following spinal cord injury improves mitochondrial function correlated with remarkable tissue sparing and functional recovery. Neuroscience 210:296–307CrossRefGoogle Scholar
  186. 186.
    Aureli T, Di Cocco ME, Capuani G, Ricciolini R, Manetti C, Miccheli A, Conti F (2000) Effect of long-term feeding with acetyl-l-carnitine on the age-related changes in rat brain lipid composition: a study by 31P NMR spectroscopy. Neurochem Res 25:395–399CrossRefGoogle Scholar
  187. 187.
    Hao J, Shen W, Sun L, Long J, Sharman E, Shi X, Liu J (2011) Mitochondrial dysfunction in the liver of type 2 diabetic Goto-Kakizaki rats: improvement by a combination of nutrients. Br J Nutr 106:648–655CrossRefGoogle Scholar
  188. 188.
    Chang B, Nishikawa M, Sato E, Utsumi K, Inoue M (2002) l-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine. Arch Biochem Biophys 405:55–64CrossRefGoogle Scholar
  189. 189.
    Furuno T, Kanno T, Arita K, Asami M, Utsumi T, Doi Y, Inoue M, Utsumi K (2001) Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition. Biochem Pharmacol 62:1037–1046CrossRefGoogle Scholar
  190. 190.
    Luo X, Reichetzer B, Trines J, Benson LN, Lehotay DC (1999) l-Carnitine attenuates doxorubicin-induced lipid peroxidation in rats. Free Radic Biol Med 26:1158–1165CrossRefGoogle Scholar
  191. 191.
    Arafa HM, Hemeida RA, Hassan MI, Abdel-Wahab MH, Badary OA, Hamada FM (2009) Acetyl-l-carnitine ameliorates caerulein-induced acute pancreatitis in rats. Basic Clin Pharmacol Toxicol 105:30–36CrossRefGoogle Scholar
  192. 192.
    Tufekci O, Gunes D, Ozoğul C, Kolatan E, Altun Z, Yilmaz O, Aktaş S, Erbayraktar Z, Kirkim G, Mutafoğlu K, Soylu A, Serbetçioğlu B, Güneri EA, Olgun N (2009) Evaluation of the effect of acetyl l-carnitine on experimental cisplatin nephrotoxicity. Chemotherapy 55:451–459CrossRefGoogle Scholar
  193. 193.
    Hota KB, Hota SK, Chaurasia OP, Singh SB (2012) Acetyl-l-carnitine-mediated neuroprotection during hypoxia is attributed to ERK1/2-Nrf2-regulated mitochondrial biosynthesis. Hippocampus 22:723–736CrossRefGoogle Scholar
  194. 194.
    Mingorance C, Duluc L, Chalopin M, Simard G, Ducluzeau PH, Herrera MD, Alvarez de Sotomayor M, Andriantsitohaina R (2012) Propionyl-l-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity. PLoS ONE 7:e34268CrossRefGoogle Scholar
  195. 195.
    Shen W, Hao J, Tian C, Ren J, Yang L, Li X, Luo C, Cotma CW, Liu J (2008) A combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. PLoS ONE 3:e2328CrossRefGoogle Scholar
  196. 196.
    El Alaoui-Talibi Z, Guendouz A, Moravec M, Moravec J (1997) Control of oxidative metabolism in volume-overloaded rat hearts: effect of propionyl-l-carnitine. Am J Physiol 272:1615–1624Google Scholar
  197. 197.
    Pasini E, Cargnoni A, Condorelli E, Marzo A, Lisciani R, Ferrari R (1992) Effect of prolonged treatment with propionyl-l-carnitine on erucic acid-induced myocardial dysfunction in rats. Mol Cell Biochem 112:117–123CrossRefGoogle Scholar
  198. 198.
    Milazzo L, Menzaghi B, Caramma I, Nasi M, Sangaletti O, Cesari M, Zanone Poma B, Cossarizza A, Antinori S, Galli M (2010) Effect of antioxidants on mitochondrial function in HIV-1-related lipoatrophy: a pilot study. AIDS Res Hum Retroviruses 26:1207–1214CrossRefGoogle Scholar
  199. 199.
    Thompson CH, Irish AB, Kemp GJ, Taylor DJ, Radda GK (1997) The effect of propionyl l-carnitine on skeletal muscle metabolism in renal failure. Clin Nephrol 47:372–378Google Scholar
  200. 200.
    Stadler DD, Chenard CA, Rebouche CJ (1993) Effect of dietary macronutrient content on carnitine excretion and efficiency of carnitine reabsorption. Am J Clin Nutr 58:868–872Google Scholar
  201. 201.
    Graziano F, Bisonni R, Catalano V, Silva R, Rovidati S, Mencarini E, Ferraro B, Canestrari F, Baldelli AM, De Gaetano A, Giordani P, Testa E, Lai V (2002) Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer 86:1854–1857CrossRefGoogle Scholar
  202. 202.
    Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud S, Shaiova L, Fleishman S, Lapin J, Klein E, Lesage P, Portenoy R, Esteban-Cruciani N (2004) l-Carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Ann N Y Acad Sci 1033:168–176CrossRefGoogle Scholar
  203. 203.
    Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud S, Lapin J, Portenoy RK, Esteban-Cruciani N (2009) l-Carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. J Pain Symptom Manage 37:622–631CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Institute of Animal Nutrition and Nutrition PhysiologyJustus-Liebig-University GiessenGiessenGermany

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