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


CONCLUSIONS
Biochemical and molecular analyses indicated a stimulation of oxidative metabolism in white blood cells through carnitine uptake.
Waldner
Raimund
R
3rd Department of Medicine, Hanusch Hospital, Vienna, Austria.
Laschan
Claudia
C
Lohninger
Alfred
A
Gessner
Martin
M
Tüchler
Heinz
H
Huemer
Marlies
M
Spiegel
Wolfgang
W
Karlic
Heidrun
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002331:Carnitine / Q000097:blood / Q000627:therapeutic use*; D002333:Carnitine Acyltransferases / Q000187:drug effects / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D000074058:Solute Carrier Family 22 Member 5; D013997:Time Factors; D014803:Vitamin B Complex / Q000627:therapeutic use*
D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D014803:Vitamin B Complex; D004317:Doxorubicin; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine