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Prevention of doxorubicin-induced cardiotoxicity by recombinant interleukin-1 in hamsters

Doxorubicin cardiotoxicity and interleukin-1

  • Research Articles
  • Published:
Biotherapy

Abstract

The major factor contributing to doxorubicin (DXR)-induced cardiotoxicity is the insufficiency of antioxidant defense mechanisms. As a model of acute cardiotoxicity with DXR, ten-week-old golden hamsters were given DXR (5 mg/kg) intravenously, and the toxicity was investigated by monitoring ECG changes. Complete A-V block and cardiac arrest on the ECG were observed in DXR-treated hamsters. DXR-induced edema and fragmentation of myofibrils were observed by electron-micrograph. Pretreatment with interleukin-1β(10 or 1μg/body) 12 or 24 hrs before prevented these changes, but pretreatment with tumor necrosis factorα had no effect.

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Abbreviations

DXR:

doxorubicin

IL-1:

interleukin-1

Mn SOD:

manganous superoxide dismutase

TNF:

tumor necrosis factor

References

  1. Pigram WJ, Fuller W, Hamilton LD. Stereochemistry of intercalation: intercalation of Daunomycin with DNA. Nat New Biol, 1972; 235: 17–9.

    PubMed  Google Scholar 

  2. Berlin V, Hanseltine WA. Reduction of Adriamycin to a sequinone-freeradical by NADPH cytochrome P-450 reductase produces DNA cleavage in a reaction mediated by molecular oxygen. J Biol Chem, 1981; 256: 4747–56.

    PubMed  Google Scholar 

  3. Tritton TR, Yee G. The anticancer agent Adriamycin can be actively cytotoxic without entering cells. Science (Wash. DC), 1982; 217: 248–50.

    Google Scholar 

  4. Goormaghtigh E, Chatelain P, Caspers J, Ruysschart JM. Evidence of a specific complex between Adriamycin and negatively charged phospholipids. Biochim Biophys Acta, 1980; 597: 1–14.

    PubMed  Google Scholar 

  5. Goodman J, Hochstein P. Generation of free radicals and lipid peroxidation by redox cycling of Adriamycin and Daunomycin. Biochem Biophys Res Commun, 1977; 77: 797–803.

    PubMed  Google Scholar 

  6. Bachur NB, Gordon SL, Gee MV, Kon H. NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals. Proc Natl Acad Sci USA, 1979; 76: 954–57.

    PubMed  Google Scholar 

  7. Fisher J, Ramakrishnan K, Becvar E. Direct enzyme-catalized reduction of anthracyclines by reduced nicotinamide adenine dinucleotide. Biochemistry, 1983; 22: 1347–55.

    PubMed  Google Scholar 

  8. Handa K, Sato S. Generation of free radicals of quinone group containing anticancer chemicals in NADPH-microsomes system as evidenced by initiation of sulfite oxidation. Gann, 1975; 66: 43–7.

    PubMed  Google Scholar 

  9. Thayer WS. Adriamycin stimulates superoxide formation in submitochondrial particles. Chem Biol Interact, 1977; 19: 265–78.

    PubMed  Google Scholar 

  10. Thornallex PJ, Dodd NJF. Free radical production from normal and adriamycin-treated rat cardiac sarcomes. Biochem Pharmacol. 1985; 34: 669–74.

    PubMed  Google Scholar 

  11. Myers CE, McGuire WP, Liss RH, Ifrim I, Grotzinger K, Youg RC. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science (Wash. DC.), 1977; 197: 165–7.

    Google Scholar 

  12. Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine. J Clin Invest, 1981; 68: 1053–64.

    PubMed  Google Scholar 

  13. Lenzhofer R, Magometshnigg D, Dudczac R, Cerni C, Bolebruch C, Moser K. Indication of reduced doxorubin-induced cardiac toxicity by additional treatment with antioxidative substances. Experientia, 1983; 39: 62–4.

    PubMed  Google Scholar 

  14. Kanter MM, Hamin RL, Unuerferth DV, Davis HW, Merola AJ. Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin. J Appl Physiol, 1985; 59: 1298–303.

    PubMed  Google Scholar 

  15. Revis NW, Marusic N. Glutathione peroxidase activity and selenium concentration in the hearts of doxorubicin-treated rabbits. J Mol Cell Cardiol, 1978; 10: 945–51.

    PubMed  Google Scholar 

  16. Wang YM, Madanat FF, Kimball JC, Gleiser CA, Ali MD, Kaufman MW, Van Eys J. Effect of vitamin E against Adriamycin-induced toxicity in rabbits. Cancer Res, 1980; 40: 1022–7.

    PubMed  Google Scholar 

  17. Wong GHW, Goeddel DV. Induction of manganous superoxide dismutase by tumor necrosis factor: Possible protective mechanism. Science, 1988; 242; 941–4.

    PubMed  Google Scholar 

  18. DiSilvestro RA, David EA, Collignon C. Interleukin 1 slowly increases lung fibroblast Cu-Zn superoxide dismutase activity levels. PSEBM, 1991; 197: 197–200.

    Google Scholar 

  19. Nishida T, Nishino L, Takano M, Kawai K, Bando K, Masui Y, Nakai S, Hirai Y. cDNA cloning of IL-1 beta from mRNA of U937 cell line. Biochem Biophys Res Commun.s 1987; 143: 345–52.

    PubMed  Google Scholar 

  20. Kikumoto Y, Hong YM, Nishida T, Nakai S, Matui Y, Hirai Y. Purification and characterization of recombinant human interleukin-1 beta produced in Escherichia coli. Biochem Biophys Res Commun. 1987; 147: 315–21.

    PubMed  Google Scholar 

  21. Yamada M, Furutani Y, Notake M, Yamagishi J, Yamayoshi M, Fukui T, Nomura H, Komiya M, Kuwashima J, Nakano K, Sohmura Y, Nakamura S. Efficient production of human tumour necrosis factor in Esherichia coli. J Biotech. 1985; 3: 141–53.

    Google Scholar 

  22. Mettler FP, Young DM, Ward JM. Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats. Cancer Res. 1977; 37: 2705–13.

    PubMed  Google Scholar 

  23. Wakabayashi T, Oki T, Tone H, Hirano S, Omori K. A comparative electron microscopic study of aclacinomycin and adriamycin cardiotoxicities in rabbits and hamsters. J Electron Microsc. 1980; 29: 106–18.

    Google Scholar 

  24. Lazzarino G, Viola AR, Mulieri L, Rotilio G, Mavelli I. Prevention by fructose-1,6-bisphosphate of cardiac oxidative damage induced in mice by subchronic doxorubicin treatment. Cancer Res.s 1987; 47: 6511–16.

    PubMed  Google Scholar 

  25. Alderton P, Gross J, Green MD. Role of (±)-1,2-bis(3.5-dioxopiperazinyl-1-yl)propane (ICRF-187) in modulating free radical scavenging enzymes in doxorubicin-induced cardiomyopathy. Cancer Res. 1990; 50: 5136–42.

    PubMed  Google Scholar 

  26. Harman EH, Schen P, Farmar RM. Influence of Pharmacologic or physiologic pretreatment on acute daunomycin cardiac toxicity in the hamster. Toxicol Applied Pharmacol. 1970; 16: 335–44.

    Google Scholar 

  27. Tone H, Hirano S, Shirai M, Kumagai H, Okajima Y, Wakabayashi T. Effect of (2″R)-4′-0-tetrahydropyranyladriamycin, a new antitumor anitibiotic, on the cardiac function of hamsters. Jap J Antibiotics, 1986; 39: 547–68.

    Google Scholar 

  28. Davies KJA, Doroshow JH, Hochstein P. Mitochondrial NADPH dehydrogenase-catalized oxygen radical production by adriamycin and the relative inactivity of 5-iminodaunorubicin. FEBS Lett, 1983; 153: 227–30.

    PubMed  Google Scholar 

  29. Wong GHW, Goeddel DV. Induction of manganous superoxide dismutase by tumor necrosis factor: Possible protective mechanism. Science, 1988; 242: 941–4.

    PubMed  Google Scholar 

  30. Matsuda A, Longo DL, Kobayashi Y, Apella E, Oppenheim JJ, Matsushima K. Induction of mitochondrial manganese superoxide dismutase by interlerkin 1. FASEB, 1988; 2: 3087–91.

    Google Scholar 

  31. Neta R, Oppenheim JJ. Cytokines in therapy of radiation injury. Blood, 1988; 72: 1093–5.

    PubMed  Google Scholar 

  32. Neta R, Douches S, Oppenheim JJ. Interleukin 1 is a radioprotector. J Immunol, 1986; 136: 2483–5.

    PubMed  Google Scholar 

  33. Laver J, Abboud M, Gasparetto C, Gillio A, Smith C, O'Reilly RJ, Moore MAS. Effects IL-1 on hematopoietic progenitores after myelosuppressive chemotherapy. Biotherapy 1989; 1: 293–300.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. The Department of Internal Medicine, Toyama Perefectural Central Hospital, Toyama, Japan

    Takashi Yoshida & Hirokazu Okumura

  2. The Third Department of Internal Medicine, Kanazawa University, School of Medicine, Kanazawa, Japan

    Hiroyasu Kaya, Yoko Okabe, Sadaya Matano, Shigeki Ohtake, Shinobu Nakamura & Tamotsu Matsuda

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  1. Takashi Yoshida
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  2. Hirokazu Okumura
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  3. Hiroyasu Kaya
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  4. Yoko Okabe
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  5. Sadaya Matano
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  6. Shigeki Ohtake
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  7. Shinobu Nakamura
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  8. Tamotsu Matsuda
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Yoshida, T., Okumura, H., Kaya, H. et al. Prevention of doxorubicin-induced cardiotoxicity by recombinant interleukin-1 in hamsters. Biotherapy 6, 125–132 (1993). https://doi.org/10.1007/BF01877425

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  • DOI: https://doi.org/10.1007/BF01877425

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