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Carnitine levels and cardiac functions in children with solid malignancies receiving doxorubicin therapySource of Support Mahidol University (2552-4)
Aim: Previous studies demonstrated l-carnitine decreasing doxorubicin-induced cardiotoxicity. Our objectives were to study carnitine levels and cardiac functions in children treated with doxorubicin and the effect of short-term l-carnitine supplements. Materials and Methods: Serial carnitine levels and cardiac functions were obtained in children with newly diagnosed solid malignancies before doxorubicin, after cumulative doses of ≥150 mg/m 2 and ≥300 mg/m 2 , respectively. Oral l-carnitine 100 mg/kg/day for 3 days were given to the children treated with doxorubicin at cumulative doses of ≥150 mg/m 2 and ≥300 mg/m 2 . Carnitine levels and cardiac functions were also obtained in those children before and after short-term oral l-carnitine at each cumulative dose of doxorubicin. Results: Five children (3 females), median age of 9.1 years (range 1.5-13 years) with newly diagnosed solid malignancies were enrolled in the study. Free carnitine (FC) tended to decrease while acyl-carnitine (AC) increased making AC/FC ratio increased after cumulative dose of ≥150 and ≥300 mg/m 2 but the statistics was not significant. Left ventricular (LV) systolic function was not significantly changed. Interestingly, LV global function (LV myocardial performance index) was significantly increased after 150 mg/m 2 (median 0.39, 0.27-0.51) and 300 mg/m 2 (median 0.46, 0.27-0.50) when compared to baseline (median 0.28, 0.14-0.48) (P=0.05). Carnitine levels and cardiac functions were not significantly changed after oral l-carnitine supplement at cumulative dose of ≥150 mg/m 2 (n=6) and ≥300 mg/m 2 (n=9). Conclusions: Carnitine levels tended to decrease after doxorubicin treatment. LV global dysfunction was documented early after doxorubicin. However, short-term l-carnitine supplement did not improve cardiac function.
Article published online:
16 August 2021
© 2011. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
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- 1 Carter SK. Adriamycin: A review. J Natl Cancer Inst 1975;55:1265-74.
- 2 Kantrowitz NE, Bristow MR. Cardiotoxicity of antitumor agents. Prog Cardiovasc Dis 1984;27:195-200.
- 3 al-Shabanah O, Mansour M, el-Kashef H, al-Bekairi A. Captopril ameliorates myocardial and hematological toxicities induced by adriamycin. Biochem Mol Biol Int 1998;45:419-27.
- 4 Huang XM, Zhu WH, Kang ML. Study on the effect of doxorubicin on expressions of genes encoding myocardial sarcoplasmic reticulum Ca2+ transport proteins and the effect of taurine on myocardial protection in rabbits. J Zhejiang Univ Sci 2003;4:114-20.
- 5 Myers C. The role of iron in doxorubicin-induced cardiomyopathy. Semin Oncol 1998;25:10-4.
- 6 Sayed-Ahmed MM, Shaarawy S, Shouman SA, Osman AM. Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine. Pharmacol Res 1999;39:289-95.
- 7 Sayed-Ahmed MM. Increased serum and cardiac acyl-carnitine/free carnitine ratio during development of doxorubicin-induced cardiotoxicity. Saudi Pharm J 2007;15:120-6.
- 8 Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: A systematic review. Health Technol Assess 2007;11:1-84.
- 9 Sayed-Ahmed MM, Shouman SA, Rezk BM, Khalifa MH, Osman AM, El-Merzabani MM. Propionyl-L-carnitine as potential protective agent against adriamycin-induced impairment of fatty acid beta-oxidation in isolated heart mitochondria. Pharmacol Res 2000;41:143-50.
- 10 Alhomida AS, Duhaiman AS, al-Jafari AA, Junaid MA. Determination of L-carnitine, acylcarnitine and total carnitine levels in plasma and tissues of camel (Camelus dromedarius). Comp Biochem Physiol B Biochem Mol Biol 1995;111:441-5.
- 11 Pastoris O, Dossena M, Foppa P, Catapano M, Arbustini E, Bellini O, et al. Effect of L carnitine on myocardial metabolism: Results of a balanced, placebo-controlled, double-blind study in patients undergoing open heart surgery. Pharmacol Res 1998;37:115-22.
- 12 Nemoto S, Yasuhara K, Nakamura K, Miyoshi Y, Sakai A. Plasma carnitine concentrations in patients undergoing open heart surgery. Ann Thorac Cardiovasc Surg 2004;10:19-22.
- 13 Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, et al. New index of combined systolic and diastolic myocardial performance: A simple and reproducible measure of cardiac function-a study in normals and dilated cardiomyopathy. J Cardiol 1995;26:357-66.
- 14 Eto G, Ishii M, Tei C, Tsutsumi T, Akagi T, Kato H. Assessment of global left ventricular function in normal children and in children with dilated cardiomyopathy. J Am Soc Echocardiogr 1999;12:1058-64.
- 15 Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: A concise review. J Mol Cell Cardiol 1987;19:817-28.
- 16 Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979;91:710-7.
- 17 Okada Y, Horikawa K, Sano M. Echocardiographic evaluation of cardiotoxicity induced by anthracycline therapy. Gan To Kagaku Ryoho 1997;24:585-9.
- 18 Senju N, Ikeda S, Koga S, Miyahara Y, Tsukasaki K, Tomonaga M, et al. The echocardiographic Tei-index reflects early myocardial damage induced by anthracyclines in patients with hematological malignancies. Heart Vessels 2007;22:393-7.
- 19 Yaris N, Akyuz C, Coskun T, Buyukpamukcu M. Serum carnitine levels of pediatric cancer patients. Pediatr Hematol Oncol 2002;19:1-8.
- 20 Yaris N, Ceviz N, Coskun T, Akytuz C, Buyukpamukcu M. Serum carnitine levels during the doxorubicin therapy. Its role in cardiotoxicity. J Exp Clin Cancer Res 2002;21:165-70.
- 21 Yoon HR, Hong YM, Boriack RL, Bennett MJ. Effect of L-carnitine supplementation on cardiac carnitine palmitoyltransferase activities and plasma carnitine concentrations in adriamycin-treated rats. Pediatr Res 2003;53:788-92.
- 22 Andrieu-Abadie N, Jaffrezou JP, Hatem S, Laurent G, Levade T, Mercadier JJ. L-carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: Role of inhibition of ceramide generation. FASEB J 1999;13:1501-10.
- 23 Goa KL, Brogden RN. L-Carnitine. A preliminary review of its pharmacokinetics, and its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism. Drugs 1987;34:1-24.
- 24 Kawasaki N, Lee JD, Shimizu H, Ueda T. Long-term L-carnitine treatment prolongs the survival in rats with adriamycin-induced heart failure. J Card Fail 1996;2:293-9.