L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria

International Journal of Cancer

Volumn 113, Issue 5, 2005, Pages 719-729

  Chang, BaoJun ^a   Nishikawa, Manabu ^a   Nishiguchi, Shuhei ^a   Inoue, Masayasu ^a  

^a OSAKA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Carcinogenesis; Chronic hepatitis; Free radical; L carnitine; Long Evans Cinnamon rats; Mitochondria

Indexed keywords

CARNITINE; COPPER; FATTY ACID; GLUTATHIONE TRANSFERASE; REACTIVE OXYGEN METABOLITE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CANCER MODEL; CELL DEATH; CHRONIC HEPATITIS; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HEPATITIS; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER MITOCHONDRION; LIVER PROTECTION; MALE; NONHUMAN; OXIDATIVE STRESS; PLACENTA; PRIORITY JOURNAL; RAT;

ANIMALS; APOPTOSIS; CARCINOMA, HEPATOCELLULAR; CARNITINE; COPPER; FATTY ACIDS, NONESTERIFIED; GLUTATHIONE TRANSFERASE; HEPATITIS; LIVER NEOPLASMS; MALE; MITOCHONDRIA; OXIDATIVE STRESS; PLACENTA; RATS; RATS, INBRED LEC; REACTIVE OXYGEN SPECIES;

EID: 11944275346     PISSN: 00207136     EISSN: None     Source Type: Journal    
DOI: 10.1002/ijc.20636     Document Type: Article

References (50)

1. Kane JM, Shears LL III, Hierholzer C II, Ambs S, Billiar TR, Posner MC. Chronic hepatitis C virus infection in humans: induction of hepatic nitric oxide synthase and proposed mechanisms for carcinogenesis. J Surg Res 1997;69:321-4.
2. Schwarz KB. Oxidative stress during viral infection: a review. Free Radic Biol Med 1996;21:641-9.
3. Beckman KB, Ames BN. Oxidative decay of DNA. J Biol Chem 1997;272:19633-6.
4. Croteau DL, Bohr VA. Repair of Oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J Biol Chem 1997;272:25409-12.
5. Shadel GS, Clayton DA. Mitochondrial DNA maintenance in vertebrates. Annu Rev Biochem 1997;66:409-35.
6. Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann NY Acad Sci 1998;854:155-70.
7. Richter C. Reactive oxygen and DNA damage in mitochondria. Mutat Res 1992;275:249-55.
8. Lenaz G. Role of mitochondria in oxidative stress and ageing. Biochim Biophys Acta 1998;1366:53-67.
9. Raha S, Robinson BH. Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 2000;25:502-8.
10. Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000;29:222-30.
11. Feig DI, Reid TM, Loeb LA. Reactive oxygen species in tumorigenesis. Cancer Res 1994;54:1890-4.
12. Trush MA, Kensler TW. An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Radic Biol Med 1991;10:201-9.
13. Wu J, Forbes JR, Chen HS, Cox DW. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene. Nat Genet 1994;7:541-5.
14. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet 1993;5:327-37.
15. Murata Y, Yamakawa E, Iizuka T, Kodama H, Abe T, Seki Y, Kodama M. Failure of copper incorporation into ceruloplasmin in the Golgi apparatus of LEC rat hepatocytes. Biochem Biophys Res Commun 1995;209:349-55.
16. Li Y, Togashi Y, Sato S, Emoto T, Kang JH, Takeichi N, Kobayashi H, Kojima Y, Une Y, Uchino J. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis: a model of Wilson's disease. J Clin Invest 1991;87:1858-61.
17. Sternlieb I, Quintana N, Volenberg I, Schilsky ML. An array of mitochondrial alterations in the hepatocytes of Long-Evans Cinnamon rats. Hepatology 1995;22:1782-7.
18. Yamamoto H, Watanabe T, Mizuno H, Endo K, Hosokawa T, Kazusaka A, Gooneratne R, Fujita S. In vivo evidence for accelerated generation of hydroxyl radicals in liver of Long-Evans Cinnamon (LEC) rats with acute hepatitis. Free Radic Biol Med 2001;30:547-54.
19. Bremer J. Carnitine metabolism and functions. Physiol Rev 1983;63:1420-80.
20. Bieber LL. Carnitine. Annu Rev Biochem 1988;57:261-83.
21. Chang B, Nishikawa M, Sato E, Utsumi K, Inoue M. L-carnitine inhibits cisplatin-induced injury of the kidney and small intestine. Arch Biochem Biophys 2002;405:55-64.
22. Furuno T, Kanno T, Arita K, Asami M, Utsumi T, Doi Y, Inoue M, Utsumi K. Role of long chain fatty acids and carnitine in mitochondrial membrane permeability transition. Biochem Pharmacol 2001;62:1037-46.
23. Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA 2002;99:1870-5.
24. Therrien G, Rose C, Butterworth J, Butterworth RF. Protective effect of L-carnitine in ammonia-precipitated encephalopathy in the porta-caval shunted rat. Hepatology 1997;25:551-6.
25. Pastorino JG, Snyder JW, Serroni A, Hoek JB, Farber JL. Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J Biol Chem 1993;268:13791-8.
26. Luo X, Reichetzer B, Trines J, Benson LN, Lehotay DC. L-carnitine attenuates doxorubicin-induced lipid peroxidation in rats. Free Radic Biol Med 1999;26:1158-65.
27. Reznick AZ, Kagan VE, Ramsey R, Tsuchiya M, Khwaja S, Serbinova EA, Packer L. Antiradical effects in L-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. Arch Biochem Biophys 1992;296:394-401.
28. Hogeboom GH. Fractionation of cell components of animal tissues. Methods Enzymol 1955;1:16-9.
29. Bradford M. Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
30. Packer L, Utsumi R, Mustafa MG. Oscillatory states of mitochondria: I, electron and energy transfer pathways. Arch Biochem Biophys 1966;117:381-93.
31. Parfait B, Rustin P, Munnich A, Rotig A. Co-amplification of nuclear pseudogenes and assessment of heteroplasmy of mitochondrial DNA mutations. Biochem Biophys Res Commun 1998;247:57-9.
32. Imada I, Sato EF, Miyamoto M, Ichimori Y, Minamiyama Y, Konaka R, Inoue M. Analysis of reactive oxygen species generated by neutrophils using a chemiluminescence probe L-012. Anal Biochem 1999;271:53-8.
33. Satoh K, Kitahara A, Soma Y, Inaba Y, Hatayama I, Sato K. Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis. Proc Natl Acad Sci USA 1985;82:3964-8.
34. Sone K, Maeda M, Wakabayashi K, Takeichi N, Mori M, Sugimura T, Nagao M. Inhibition of hereditary hepatitis and liver tumor development in Long-Evans cinnamon rats by the copper-chelating agent trientine dihydrochloride. Hepatology 1996;23:764-70.
35. Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 1995;18:321-36.
36. Treem WR, Sokol RJ. Disorders of the mitochondria. Semin Liver Dis 1998;18:237-53.
37. Britton RS. Metal-induced hepatotoxicity. Semin Liver Dis 1996;16:3-12.
38. Moraes CT, Ricci E, Petruzzella V, Shanske S, DiMauro S, Schon EA. Bonilla E. Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nat Genet 1992;1:359-67.
39. Esposito LA, Melov S, Panov A, Cottrell BA, Wallace DC. Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci USA 1999;96:4820-5.
40. Madesh M, Balasubramanian KA. Activation of liver mitochondrial phospholipase A2 by superoxide. Arch Biochem Biophys 1997;346:187-92.
41. Pacifici EH, McLeod LL, Sevanian A. Lipid hydroperoxide-induced peroxidation and turnover of endothelial cell phospholipids. Free Radic Biol Med 1994;17:297-309.
42. Sultan A, Sokolove PM. Free fatty acid effects on mitochondrial permeability: an overview. Arch Biochem Biophys 2001;386:52-61.
43. Toyokuni S, Sagripanti JL. Association between 8-hydroxy-2′- deoxyguanosine formation and DNA strand breaks mediated by copper and iron. Free Radic Biol Med 1996;20:859-64.
44. Lloyd DR, Phillips DH. Oxidative DNA damage mediated by copper-(II), iron(II) and nickel(II) fenton reactions: evidence for site-specific mechanisms in the formation of double-strand breaks, 8-hydroxydeoxyguanosine and putative intrastrand cross-links. Mutat Res 1999;424:23-36.
45. Nishikawa M, Nishiguchi S, Shiomi S, Tamori A, Koh N, Takeda T, Kubo S, Hirohashi K, Kinoshita H, Sato E, Inoue M. Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma. Cancer Res 2001;61:1843-5.
46. Krahenbuhl S, Brass EP, Hoppel CL. Decreased carnitine biosynthesis in rats with secondary biliary cirrhosis. Hepatology 2000;31:1217-23.
47. Kuwajima M, Lu K, Sei M, Ono A, Hayashi M, Ishiguro K, Ozaki K, Hotta K, Okita K, Murakami T, Miyagawa J, Narama I, et al. Characteristics of cardiac hypertrophy in the juvenile visceral steatosis mouse with systemic carnitine deficiency. J Mol Cell Cardiol 1998; 30:773-81.
48. Kuwajima M, Horiuchi M, Harashima H, Lu K, Hayashi M, Sei M, Ozaki K, Kudo T, Kamido H, Ono A, Saheki T, Shima K. Cardiomegaly in the juvenile visceral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection. FEBS Lett 1999;443:261-6.
49. Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann NY Acad Sci 2002;959:133-66.
50. Arduini A. Carnitine and its acyl esters as secondary antioxidants? Am Heart J 1992;123:1726-7.