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Randomized Controlled Trial
. 2006 Feb;132(2):121-8.
doi: 10.1007/s00432-005-0054-8. Epub 2005 Nov 8.

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

Raimund Waldner  1 , Claudia Laschan, Alfred Lohninger, Martin Gessner, Heinz Tüchler, Marlies Huemer, Wolfgang Spiegel, Heidrun Karlic
Affiliations
Randomized Controlled Trial

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

Raimund Waldner et al. J Cancer Res Clin Oncol. 2006 Feb.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: Biochemical and molecular analyses indicated a stimulation of oxidative metabolism in white blood cells through carnitine uptake.

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Figures

Fig. 1
Fig. 1
Relative mRNA levels (normal WBC=100%) of carnitine acyltransferases (CPT1A, CPT1B, CRAT and CPT2) as well as carnitine transporter OCTN2 are shown for the placebo group (a) and the carnitine group (b). Relative mRNA levels of CPT1A was significantly increased in the carnitine group (P<0.001). Serum carnitine levels (FC free carnitine, KA short chain acyl carnitines, GC total carnitine) and two types of triglycerides (CTGL50 and CTGL54) are shown for the placebo group (c) and the carnitine group (d). Following carnitine therapy at time points (1) and (2), levels of free carnitine (FC) and total carnitine (GC) in plasma were significantly higher in the carnitine group as compared to the placebo group (P<0.001). After therapy, triglycerides, from groups CTGL50and CTGL54, were significantly higher in the carnitine group as compared to the placebo group. Differences between carnitine group and placebo group after therapy were 24.2 vs 36.3 mg/ml (P=0.03) for CTGL50 and 17.8 vs 24.5 mg/ml (P=0.05) for CTGL54. Box plots are displaying medians (middle line), 25th and 75th percentiles (boxes) and upper and lower extremes (whiskers). The ° symbols represent outliers
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