Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells

We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have...

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Bibliographic Details
Published in:Biochemical journal 1985-06, Vol.228 (2), p.513-516
Main Authors: Nikula, P, Ruohola, H, Alhonen-Hongisto, L, Jänne, J
Format: Article
Language:English
Subjects:
Animals
Carnitine - pharmacology
Cells, Cultured
Guanidines - pharmacology
Leukemia L1210 - pathology
Mice
Microscopy, Electron
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria - ultrastructure
Mitoguazone - pharmacology
Oxidation-Reduction
Palmitic Acid
Palmitic Acids - metabolism
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Summary:We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj2280513