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. 1985 Jun 1;228(2):513–516. doi: 10.1042/bj2280513

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

P Nikula, H Ruohola, L Alhonen-Hongisto, J Jänne
PMCID: PMC1145010  PMID: 3837667

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.

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Selected References

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  1. Byczkowski J. Z., Porter C. W. Interactions between bis(guanylhydrazones) and polyamines in isolated mitochondria. Gen Pharmacol. 1983;14(6):615–621. doi: 10.1016/0306-3623(83)90158-1. [DOI] [PubMed] [Google Scholar]
  2. Byczkowski J. Z., Salamon W., Harlos J. P., Porter C. W. Actions of bis(guanylhydrazones) on isolated rat liver mitochondria. Biochem Pharmacol. 1981 Oct;30(20):2851–2860. doi: 10.1016/0006-2952(81)90425-1. [DOI] [PubMed] [Google Scholar]
  3. Feuerstein B., Porter C. W., Dave C. A selective effect of methylglyoxal-bis(guanylhydrazone) on the synthesis of mitochondrial DNA of cultured L1210 leukemia cells. Cancer Res. 1979 Oct;39(10):4130–4137. [PubMed] [Google Scholar]
  4. Jänne J., Alhonen-Hongisto L., Seppänen P., Siimes M. Use of polyamine antimetabolites in experimental tumours and in human leukemia. Med Biol. 1981 Dec;59(5-6):448–457. [PubMed] [Google Scholar]
  5. Kallio A., Seppänen P., Alhonen-Hongisto L., Jänne J. Modulation of the tissue disposition of methylglyoxal bis(guanylhydrazone) in mice by polyamine depletion and by polyamine administration. Cancer Res. 1983 Jan;43(1):324–327. [PubMed] [Google Scholar]
  6. Mikles-Robertson F., Feuerstein B., Dave C., Porter C. W. The generality of methylglyoxal bis(guanylhydrazone)-induced mitochondrial damage and the dependence of this effect on cell proliferation. Cancer Res. 1979 Jun;39(6 Pt 1):1919–1926. [PubMed] [Google Scholar]
  7. Nikula P., Alhonen-Hongisto L., Seppänen P., Jänne J. Inhibition of long-chain fatty acid oxidation by methylglyoxal bis(guanylhydrazone). Biochem Biophys Res Commun. 1984 Apr 16;120(1):9–14. doi: 10.1016/0006-291x(84)91406-2. [DOI] [PubMed] [Google Scholar]
  8. Pathak S. N., Porter C. W., Dave C. Morphological evidence for an antimitochondrial action by methylglyoxal-bis(guanylhydrazone). Cancer Res. 1977 Jul;37(7 Pt 1):2246–2250. [PubMed] [Google Scholar]
  9. Pine M. J., DiPaolo J. A. The antimitochondrial action of 2-choloro-4', 4"-bis(2-imidazolin-2-yl)terephthalanilide and methylglyoxal bis(guanylhydrazone). Cancer Res. 1966 Jan;26(1):18–25. [PubMed] [Google Scholar]
  10. Pleshkewych A., Maurer T. C., Porter C. W. Ultrastructural changes in the mitochondria of intestinal epithelium of rodents treated with methylglyoxal-bis(guanylhydrazone). Cancer Res. 1983 Feb;43(2):646–652. [PubMed] [Google Scholar]
  11. Seppänen P., Alhonen-Hongisto L., Pösö H., Jänne J. Sensitive enzymic determination of methylglyoxal bis(guanylhydrazone) in cultured cells and in animal tissues. FEBS Lett. 1980 Feb 25;111(1):99–103. doi: 10.1016/0014-5793(80)80770-8. [DOI] [PubMed] [Google Scholar]
  12. Warrell R. P., Jr, Burchenal J. H. Methylglyoxal-bis(guanylhydrazone) (Methyl-GAG): current status and future prospects. J Clin Oncol. 1983 Jan;1(1):52–65. doi: 10.1200/JCO.1983.1.1.52. [DOI] [PubMed] [Google Scholar]
  13. Williams-Ashman H. G., Schenone A. Methyl glyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylases. Biochem Biophys Res Commun. 1972 Jan 14;46(1):288–295. doi: 10.1016/0006-291x(72)90661-4. [DOI] [PubMed] [Google Scholar]

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