Effect of acetyl-L-carnitine on leukemia L1210 resistant to mitoxantrone.
Supportive care in tumour chemotherapy is a subject of intensive research. The complications of cytostatic therapy are a cause of extensive research of their pharmacological interactions and side effects. The immunologic and biochemical changes accompanying tumours are the factor that is most responsible for the worsening of the physiology of the host. Regimens containing carnitine and it's acetyl-derivative are used in many cases, among others even for preventing hepatotoxicity. Our hypothesis was to verify the supporting metabolic effects of acetyl-L-carnitine hydrochloride (ALC) in combined therapy with mitoxantrone (MX) and hepatotoxic cytostatic drugs including alkylating agents. This present report describes the effect of ALC in combination with MX on DBA/2 male mice bearing a transplantable L1210 leukemia resistant to MX. The criterion for evaluation of effect was the length of survival time of experimental animals. The proportional-hazards model quadratic in the drug dose (7) was used for survival time evaluation and optimal dose calculation. The hazard functions and the index of relative hazard were determined using Weibull distribution after logarithmic transformation of the entered data in each particular group. The dose-response curve was represented by a second-degree polynomial without absolute term. The combination therapy revealed that the optimal dose of ALC was 186 mg/kg s.c. This relation is shown in Fig.1. A significant effect of ALC (s.c.) in combined therapy with MX (6 mg/kg i.v.) given to animals bearing an experimental form of leukemia L1210/MX resistant to MX was proven at a level of probability p < or = 0.001. The effect of ALC in monotherapy was not demonstrable.
Niang
M
M
Department of Medical Biochemistry, Charles University Prague, Faculty of Medicine in Hradec Králové. niang@lfhk.cuni.cz
Mĕlka
M
M
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008942:Mitoxantrone / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D000108:Acetylcarnitine; D008942:Mitoxantrone