Effects of doxorubicin-containing chemotherapy and a combination with L-carnitine on oxidative metabolism in patients with non-hodgkin lymphoma

• Published in: Journal of cancer research and clinical oncology Vol. 132; no. 2; pp. 121 - 128
• Main Authors: WALDNER, Raimund, LASCHAN, Claudia, LOHNINGER, Alfred, GESSNER, Martin, TUCHLER, Heinz, HUEMER, Marlies, SPIEGEL, Wolfgang, KARLIC, Heidrun
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-02-2006; Springer Nature B.V
• Subjects: Amino acids; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carnitine - blood; Carnitine - therapeutic use; Carnitine Acyltransferases - drug effects; Carnitine Acyltransferases - metabolism; Carnitine O-Palmitoyltransferase - metabolism; Chemotherapy; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes - drug effects; Leukocytes - metabolism; Lipid Peroxidation - drug effects; Lymphoma; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - metabolism; Medical sciences; Metabolism; Oncology; Organic Cation Transport Proteins - metabolism; Oxidation; Oxidation-Reduction - drug effects; Pharmacology. Drug treatments; RNA, Messenger - drug effects; Solute Carrier Family 22 Member 5; Time Factors; Vitamin B Complex - therapeutic use; Antineoplastic agent; Human; DNA topoisomerase (ATP-hydrolysing); Drug combination; Enzyme; Oxidative metabolism; Enzyme inhibitor; Malignant hemopathy; Non Hodgkin lymphoma; Metabolism; Doxorubicin; Carnitine; Isomerases; Anthracycline; Aminoacid; Lymphoproliferative syndrome; L-Carnitine; Anthracyclins; Combined treatment; Pharmacokinetics
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-005-0054-8

Chemotherapy regimens based on anthracycline (doxorubicin) are well established in lymphoma therapy. The purpose of this study was to examine the effects of L-carnitine with a view to reducing cytotoxic side-effects.
20 patients were scheduled to receive 3 g L-carnitine before each chemotherapy cycle, followed by 1 g L-carnitine/day during the following 21 days, while 20 patients received a placebo (randomized controlled trial). The plasma lipid profile and relative mRNA levels of key enzymes of oxidative metabolism (carnitine acyltransferases) were measured at three points of time. In addition to the clinical parameters we used the mRNA of white blood cells to evaluate the toxic effects on cardiomyocytes.
In the present study no cardiotoxicity of anthracycline therapy was detected. Carnitine treated patients showed a rise in plasma carnitine which led to an increase of relative mRNA levels from CPT1A (liver isoform of carnitine palmitoyltransferase) and OCTN2 (carnitine transporter). Following chemotherapy, an activation of carnitine acyltransferases was associated with a stimulation of OCTN2 in both groups.
Biochemical and molecular analyses indicated a stimulation of oxidative metabolism in white blood cells through carnitine uptake.