Antineoplastic activity of three ruthenium derivatives against chemically induced colorectal carcinoma in rats View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1992-03

AUTHORS

Matthias H. Seelig, Martin R. Berger, Bernhard K. Keppler

ABSTRACT

The antineoplastic activity of the ruthenium complexestrans-imidazolium[tetrachlorobisimidazoleruthenate(III)], HIm(RuIm2Cl4),trans-indazolium-[tetrachlorobis(1H-indazole)ruthenate(III,N2)], HInd [RuInd2Cl4(N2)], andtrans-indazolium[tetrachlorobis(2H-indazole)ruthenate(III,N1)], HInd[RuInd2Cl4-(N1)] was assessed in acetoxymethylmethylnitrosamine-induced autochthonous colorectal carcinomas of Sprague-Dawley rats. The model is not sensitive to clinically established antineoplastic agents, including cisplatin. An exception is the combination therapy with 5-fluorouracil/leucovorin, which shows moderate activity against the tumour model. In contrast to this general trend, the new substances were all active against this tumour. HIm(RuIm2Cl4) was very effective at all dosages applied (7.5 mg/kg, 5.3 mg/kg, and 3.8 mg/kg), as indicated by percentage treated/control (T/C values of 23%, 34.5%, and 44%. Toxicity was considerable as shown by a body weight change of −30%, −19%, and −9%. Nevertheless, the medium dose seems to be the optimum in terms of mortality (0% vs 15% in the control group), whereas at the highest dose, mortality increased as a result of substance toxicity, and at the lowest dose mortality increased through tumor growth combined with substance toxicity.HInd[RuInd2Cl4(N2)] showed high efficacy at the highest dosage of 13 mg/kg, reaching a T/C value of 27% combined with 0% mortality versus 15% in the control group. In equimolar dosages (10 mg/kg, 7.1 mg/kg and 5.1 mg/kg), the compound is not as active as HIm-(RuIm2Cl4), as indicated by T/C values of 50.2%, 45.7%, and 38.6%. HInd[RuInd2Cl4(N1)] was slightly but not significantly better than HInd[RuInd2Cl4(N2)] at a dosage of 7.1 mg/kg and is advantageous over combination therapy with 5-fluorouracil and leucovorin (20/20 mg/kg) in terms of efficacy (T/C=37.6% versus 44.7%) and mortality (6% versus 33.3%). More... »

PAGES

195-200

References to SciGraph publications

  • 1987-07. Comparative antitumor activity of ruthenium derivatives with 5′-deoxy-5-fluorouridine in chemically induced colorectal tumors in SD rats in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1983-01. Antitumor activity of cis-dihalogenobis(1-phenyl-1,3-butanedionato)titanium(IV) compounds in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1986. Maligne Tumoren des Kolons in CHIRURGISCHE ONKOLOGIE
  • 1989. New Ruthenium Complexes for the Treatment of Cancer in RUTHENIUM AND OTHER NON-PLATINUM METAL COMPLEXES IN CANCER CHEMOTHERAPY
  • 1975-10. Evaluation of endoscopic examination of colon tumors in rats in DIGESTIVE DISEASES AND SCIENCES
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf01410134

    DOI

    http://dx.doi.org/10.1007/bf01410134

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053560513

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/1548284


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