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l-Carnitine mediates protection against DNA damage in lymphocytes of aged rats

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Abstract

It has been proposed that age-associated disorders are related to a time-dependent shift in the antioxidant/prooxidant balance towards oxidative damage. Increased production of oxidants in vivo can cause damage to intracellular macromolecules such as DNA, proteins and lipids, which can in turn lead to oxidative injury. Carnitine is a vitamin-like compound that serves as a carrier to transport long-chain fatty acids into the mitochondria for β-oxidation. In the present study, the effect of l-carnitine, a widely recognized essential nutrient, was evaluated on the status of lipid peroxidation and certain antioxidant enzymes and DNA damage in lymphocytes with relation to age in male wistar rats. The levels of lipid peroxides were remarkably increased whereas, the activities of antioxidant enzymes were significantly decreased in aged control animals when compared to younger controls. In aged animals, administration of l-carnitine for 21 days significantly decreased the levels of lipid peroxides and improved the activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. l-Carnitine enhanced T-cell proliferative responses as evaluated by T-cell proliferation assay using [3H] thymidine incorporation and also significantly reduced DNA damage, apoptosis and TNF-α level in lymphocytes of aged animals. Our results suggest that l-carnitine may have a vital role in improving functions in the cells of the immune system particularly the lymphocytes possibly through its antioxidant action.

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References

  • Afanas’ev IB (2005) Free radical mechanisms of aging processes under physiological conditions. Biogerontology 6:283–290. doi:10.1007/s10522-005-2626-z

    Article  PubMed  CAS  Google Scholar 

  • Alvarado C, Alvarez P, Puerto M, Gausseres N, Jimenez L, De la Fuente M (2006) Oxidative stress in leukocytes from young prematurely aging mice is reversed by supplementation with biscuits rich in antioxidants. Dev Comp Immunol 30:1168–1180. doi:10.1016/j.dci.2006.03.004

    Article  PubMed  CAS  Google Scholar 

  • Arivazhagan P, Thilakavathy T, Panneerselvam C (2000) Antioxidant lipoate and tissue antioxidants in aged rats. J Nutr Biochem 11:122–127. doi:10.1016/S0955-2863(99)00079-0

    Article  PubMed  CAS  Google Scholar 

  • Barja G (2004) Free radicals and aging. Trends Neurosci 27:595–600. doi:10.1016/j.tins.2004.07.005

    Article  PubMed  CAS  Google Scholar 

  • Barnett YA, King CM (1995) An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. Mutat Res 338:115–128

    PubMed  CAS  Google Scholar 

  • Benencia F, Courreges MC, Coulombie FC (2000) In vivo and in vitro immunomodulatory activities of Trichilia glabra aqueous leaf extracts. J Ethnopharmacol 69:199–205. doi:10.1016/S0378-8741(99)00010-0

    Article  PubMed  CAS  Google Scholar 

  • Boerrigter ME, Franceschi C, Arrigoni-Martelli E, Wei JY, Vijg J (1993) The effect of l-carnitine and acetyl-l-carnitine on the disappearance of DNA single-strand breaks in human peripheral blood lymphocytes. Carcinogenesis 14:2131–2136. doi:10.1093/carcin/14.10.2131

    Article  PubMed  CAS  Google Scholar 

  • Boyum A (1968) Separation of leukocytes from blood and bone marrow. Introduction. Scand J Clin Lab Invest Suppl 97:7

    PubMed  CAS  Google Scholar 

  • Branca D, Di LF, Scutari G, Toninello A, Siliprandi N (1986) Stabilizing action of l-carnitine on the energy-linked processes of mitochondria isolated from perfused rat liver. Biochem Pharmacol 35:2839–2841. doi:10.1016/0006-2952(86)90201-7

    Article  PubMed  CAS  Google Scholar 

  • Calabrese V, Stella AMG, Calvani M, Butterfield DA (2007) Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem 17:73–88. doi:10.1016/j.jnutbio.2005.03.027

    Article  CAS  Google Scholar 

  • Carlberg I, Mannervik B (1975) Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem 250:5475–5480

    PubMed  CAS  Google Scholar 

  • Chandra RK (1992) Nutrition and immunity in the elderly. Nutr Rev 50:367–371

    PubMed  CAS  Google Scholar 

  • Cifone MG, Alesse E, Di ML, Ruggeri B, Zazzeroni F, Moretti S et al (1997) Effect of l-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from AIDS patients. Proc Assoc Am Physicians 109:146–153

    PubMed  CAS  Google Scholar 

  • Clark RM, Balakrishnan A, Waters D, Aggarwal D, Owen KQ, Koo SI (2007) l-Carnitine increases liver alpha-tocopherol and lowers liver and plasma triglycerides in aging ovariectomized rats. J Nutr Biochem 18:623–628. doi:10.1016/j.jnutbio.2006.11.007

    Article  PubMed  CAS  Google Scholar 

  • De la Fuente M (2002) Effects of antioxidants on immune system ageing. Eur J Clin Nutr 56:S5–S8

    Article  CAS  Google Scholar 

  • De la Fuente M, Hernanz A, Guayerbas N, Alvarez P, Alvarado C (2004) Changes with age in peritoneal macrophage functions. Implication of leukocytes in the oxidative stress of senescence. Cell Mol Biol 50:683–690

    Google Scholar 

  • De SC, 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 8:655–660

    Google Scholar 

  • Elmadfa I, Meyer AL (2008) Body composition, changing physiological functions and nutrient requirements of the elderly. Ann Nutr Metab 52:2–5. doi:10.1159/000115339

    Article  PubMed  CAS  Google Scholar 

  • Engels WR, Johnson-Schlitz D, Flores C, White L, Preston CR (2007) A third link connecting aging with double strand break repair. Cell Cycle 6:131–135

    PubMed  CAS  Google Scholar 

  • Galli G, Fratelli M (1993) Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: inhibition by l-acetylcarnitine. Exp Cell Res 204:54–60. doi:10.1006/excr.1993.1008

    Article  PubMed  CAS  Google Scholar 

  • Garcia CL, Filippi S, Mosesso P, Calvani M, Nicolai R, Mosconi L et al (2006) The protective effect of l-carnitine in peripheral blood human lymphocytes exposed to oxidative agents. Mutagenesis 21:21–27. doi:10.1093/mutage/gei065

    Article  PubMed  CAS  Google Scholar 

  • Gohel A, McCarthy MB, Gronowicz G (1999) Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. Endocrinology 140:5339–5347. doi:10.1210/en.140.11.5339

    Article  PubMed  CAS  Google Scholar 

  • Grigolo B, Borzi RM, Mariani E, Monaco MC, Cattini L, Porstmann T et al (1994) Intracellular Cu/Zn superoxide dismutase levels in T and non-T cells from normal aged subjects. Mech Ageing Dev 73:27–37. doi:10.1016/0047-6374(94)90035-3

    Article  PubMed  CAS  Google Scholar 

  • Gruver AL, Hudson LL, Sempowski GD (2007) Immunosenescence of ageing. J Pathol 211:144–156. doi:10.1002/path.2104

    Article  PubMed  CAS  Google Scholar 

  • Gulcin I (2006) Antioxidant and antiradical activities of l-carnitine. Life Sci 78:803–811. doi:10.1016/j.lfs.2005.05.103

    Article  PubMed  CAS  Google Scholar 

  • Hao J, Shen W, Tian C, Liu Z, Ren J, Luo C, Long J, Sharman E, Liu J (2008) Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats. J Cell Mol Med. doi:10.1111/j.1582-4934.2008.00342.X

    Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:98–300

    Google Scholar 

  • Ito Y, Kajkenova O, Feuers RJ, Udupa KB, Desai VG, Epstein J et al (1998) Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils. J Gerontol A Biol Sci Med Sci 53:M169–M175

    PubMed  CAS  Google Scholar 

  • Izgut-Uysal VN, Agac A, Karadogan I, Derin N (2003) Effects of l-carnitine on neutrophil functions in aged rats. Mech Ageing Dev 124:341–347. doi:10.1016/S0047-6374(03)00004-6

    Article  PubMed  CAS  Google Scholar 

  • Janssens GP, Mast J, Goddeeris BM, Cox E, Hesta M, De Wilde RO (2000) Enhanced specific antibody response to bovine serum albumin in pigeons due to l-carnitine supplementation. Br Poult Sci 41:448–453. doi:10.1080/713654972

    Article  PubMed  CAS  Google Scholar 

  • Jiang J, Gross D, Elbaum P, Murasko DM (2007) Aging affects initiation and continuation of T cell proliferation. Mech Ageing Dev 128:332–339. doi:10.1016/j.mad.2007.02.002

    Article  PubMed  CAS  Google Scholar 

  • King CM, Bristow-Craig HE, Gillespie ES, Barnett YA (1997) In vivo antioxidant status, DNA damage, mutation and DNA repair capacity in cultured lymphocytes from healthy 75- to 80-year-old humans. Mutat Res 377:137–147. doi:10.1016/S0027-5107(97)00072-9

    PubMed  CAS  Google Scholar 

  • Kirkman HN, Gaetani GF (1984) Catalase: a tetrameric enzyme with four tightly bound molecules of NADPH. Proc Natl Acad Sci USA 81:4343–4347. doi:10.1073/pnas.81.14.4343

    Article  PubMed  CAS  Google Scholar 

  • Koudelova J, Mourek J, Drahota Z, Rauchova H (1994) Protective effect of carnitine on lipoperoxide formation in rat brain. Physiol Res 43:387–389

    PubMed  CAS  Google Scholar 

  • Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958. doi:10.1016/0006-291X(76)90747-6

    Article  PubMed  CAS  Google Scholar 

  • Makinodan T (1995) Patterns of age-related immunologic changes. Nutr Rev 53:S27–S31

    Article  PubMed  CAS  Google Scholar 

  • Mansour HH (2006) Protective role of carnitine ester against radiation-induced oxidative stress in rats. Pharmacol Res 54:165–171. doi:10.1016/j.phrs.2006.04.003

    Article  PubMed  CAS  Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474. doi:10.1111/j.1432-1033.1974.tb03714.x

    Article  PubMed  CAS  Google Scholar 

  • McMackin CJ, Widlansky ME, Hamburg NM, Huang AL, Weller S, Holbrook M et al (2007) Effect of combined treatment with alpha-Lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in patients with coronary artery disease. J Clin Hypertens 9:249–255

    CAS  Google Scholar 

  • Moron MS, DePierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78

    PubMed  CAS  Google Scholar 

  • Mutlu-Turkoglu U, Ilhan E, Oztezcan S, Kuru A, Aykac-Toker G, Uysal M (2003) Age-related increases in plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in elderly subjects. Clin Biochem 36:397–400. doi:10.1016/S0009-9120(03)00035-3

    Article  PubMed  CAS  Google Scholar 

  • Oyeyinka GO, Salimonu LS, Ladipo OA, Ashaye AO (1995) Leukocyte migration inhibition studies and neutrophil cell function during aging in Nigerians. Mech Ageing Dev 85:83–93. doi:10.1016/0047-6374(95)01650-3

    Article  PubMed  CAS  Google Scholar 

  • Rani PJ, Panneerselvam C (2002) Effect of l-carnitine on brain lipid peroxidation and antioxidant enzymes in old rats. J Gerontol A Biol Sci Med Sci 57:B134–B137

    PubMed  Google Scholar 

  • Rebouche CJ (1992) Carnitine function and requirements during the life cycle. FASEB J 6:3379–3386

    PubMed  CAS  Google Scholar 

  • Reznick AZ, Kagan VE, Ramsey R, Tsuchiya M, Khwaja S, Serbinova EA et al (1992) Antiradical effects in l-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. Arch Biochem Biophys 296:394–401. doi:10.1016/0003-9861(92)90589-O

    Article  PubMed  CAS  Google Scholar 

  • Sakai S, Moriguchi S (1997) Long-term feeding of high vitamin E diet improves the decreased mitogen response of rat splenic lymphocytes with aging. J Nutr Sci Vitaminol (Tokyo) 43:113–122

    CAS  Google Scholar 

  • Semsei I, Rao G, Richardson A (1991) Expression of superoxide dismutase and catalase in rat brain as a function of age. Mech Ageing Dev 58:13–19. doi:10.1016/0047-6374(91)90116-H

    Article  PubMed  CAS  Google Scholar 

  • Sener G, Eksioglu-Demiralp E, Cetiner M, Ercan F, Sirvanci S, Gedik N et al (2006) l-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell Biol Toxicol 22:47–60. doi:10.1007/s10565-006-0025-0

    Article  PubMed  CAS  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191. doi:10.1016/0014-4827(88)90265-0

    Article  PubMed  CAS  Google Scholar 

  • Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394. doi:10.1016/0003-2697(72)90132-7

    Article  PubMed  CAS  Google Scholar 

  • Tang Y, Di PL, Feng Y, Wang X (2000) Increased TNF-alpha and PGI(2), but not NO release from macrophages in 18-month-old rats. Mech Ageing Dev 114:79–88. doi:10.1016/S0047-6374(00)00090-7

    Article  PubMed  CAS  Google Scholar 

  • Tewari S, Seshadri M, Poduval TB (1982) Migration inhibition of normal rat thymocytes as an in vitro method for detecting cell-mediated immunity in rat and mouse. J Immunol Methods 51:231–239. doi:10.1016/0022-1759(82)90262-9

    Article  PubMed  CAS  Google Scholar 

  • Thangasamy T, Marimuthu S, Sittadjody S, Jeyakumar P, Joyee AG, Mendoza E et al (2008) Role of l-carnitine in the modulation of immune response in aged rats. Clin Chim Acta 389:19–24

    Article  PubMed  CAS  Google Scholar 

  • Vescovo G, Ravara B, Gobbo V, Sandri M, Angelini A, Della BM et al (2002) l-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure. Am J Physiol Cell Physiol 283:C802–C810

    PubMed  CAS  Google Scholar 

  • Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15:212–216. doi:10.1016/0006-2944(76)90049-1

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors are grateful to the financial support offered by Council for Scientific and Industrial Research (CSIR, New Delhi, India). There are no conflicts of interest financial or otherwise. The work and manuscript was by Thangasamy T., Jeyakumar P. contributed to the lymphocyte proliferation study and assisted all cell culture studies, Sittadjody S. assisted with the Leukocyte migration inhibition studies and carried out the statistical analysis, Joyee A. G. assisted with the apoptosis studies and all cell culture studies and Chinnakannu P. served as the Principal Investigator.

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Correspondence to Thilakavathy Thangasamy.

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Thangasamy, T., Jeyakumar, P., Sittadjody, S. et al. l-Carnitine mediates protection against DNA damage in lymphocytes of aged rats. Biogerontology 10, 163–172 (2009). https://doi.org/10.1007/s10522-008-9159-1

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