Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells
- 1 June 1985
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 228 (2) , 513-516
- https://doi.org/10.1042/bj2280513
Abstract
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.This publication has 13 references indexed in Scilit:
- ULTRASTRUCTURAL-CHANGES IN THE MITOCHONDRIA OF INTESTINAL EPITHELIUM OF RODENTS TREATED WITH METHYLGLYOXAL-BIS(GUANYLHYDRAZONE)1983
- MODULATION OF THE TISSUE DISPOSITION OF METHYLGLYOXAL BIS(GUANYLHYDRAZONE) IN MICE BY POLYAMINE DEPLETION AND BY POLYAMINE ADMINISTRATION1983
- Use of polyamine antimetabolites in experimental tumours and in human leukemia.1981
- Actions of bis(guanylhydrazones) on isolated rat liver mitochondriaBiochemical Pharmacology, 1981
- Sensitive Enzymic determination of methylglyoxal bis(guanylhydrazone) in cultured cells and in animal tissuesFEBS Letters, 1980
- GENERALITY OF METHYLGLYOXAL BIS-(GUANYLHYDRAZONE)-INDUCED MITOCHONDRIAL DAMAGE AND THE DEPENDENCE OF THIS EFFECT ON CELL-PROLIFERATION1979
- SELECTIVE EFFECT OF METHYLGLYOXAL-BIS(GUANYLHYDRAZONE) ON THE SYNTHESIS OF MITOCHONDRIAL-DNA OF CULTURED L1210 LEUKEMIA-CELLS1979
- MORPHOLOGICAL EVIDENCE FOR AN ANTI-MITOCHONDRIAL ACTION BY METHYLGLYOXAL-BIS(GUANYLHYDRAZONE)1977
- Methyl glyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylasesBiochemical and Biophysical Research Communications, 1972
- ANTIMITOCHONDRIAL ACTION OF 2-CHLORO-4',4''-BIS(2-IMIDAZOLIN-2-YL)TEREPHTHALANILIDE AND METHYLGLYOXAL BIS(GUANYLHYDRAZONE)1966