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Effect of cisplatin on mitochondrial protein, glutathione, and succinate dehydrogenase in Dalton lymphoma-bearing mice

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Abstract

Cisplatin treatment of tumor-bearing mice resulted a significant decrease of protein in the tissues studied (liver, kidney, and Dalton lymphoma) and also in their mitochondrial fractions. As compared to respective tissues, the protein decrease was noted to be more conspicuous in their mitochondrial fractions. Similarly, mitochondrial glutathione also decreased significantly in the tissues. However, succinate dehydrogenase activity was selectively decreased in the kidney and Dalton lymphoma cells, whereas in liver it remained almost unchanged. An increase in serum urea concentration and kidney mitochondrial lipid peroxidation was also observed after cisplatin treatment. It is suggested that the cisplatin-induced biochemical changes in mitochondria involving mitochondrial protein, glutathione, and succinate dehydrogenase could be the important potent cellular sites contributing to toxicity/cytotoxicity after cisplatin treatment.

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References

  • Allen JA, Coombs MM. Covalent binding of polycyclic aromatic compounds to mitochondrial and nuclear DNA. Nature. 1980;287:244-5.

    Article  PubMed  CAS  Google Scholar 

  • Beatrice MC, Stiers DL, Pfeiffer DR. The role of glutathione in the retention of Ca2+ by liver mitochondria. J Biol Chem. 1984;259:1279-87.

    PubMed  CAS  Google Scholar 

  • Beltrame M, Sindellari L, Arslan P. Effects of newly synthesised platinum(II) complexes on mitochondrial functions. Chem Biol Interact. 1984;50:247-54.

    Article  PubMed  CAS  Google Scholar 

  • Brady HR, Kone BC, Stromski ME, Zeidel ML, Giebisch G, Gullans SR. Mitochondrial injury: an early event in cisplatin toxicity to renal proximal tubules. Am J Physiol. 1990;258:F1181-7.

    PubMed  CAS  Google Scholar 

  • Brown GJ Jr and Cohen PP. Comparative biochemistry of urea synthesis: I. Method for the quantitative assay of urea cycle in liver. J Biol Chem. 1959;234:1769-74.

    PubMed  CAS  Google Scholar 

  • Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10.

    Article  PubMed  CAS  Google Scholar 

  • Cavalli LR, Liang BC. Mutagenesis, tumorigenicity, and apoptosis: are the mitochondria involved? Mutat Res. 1998;398: 19-26.

    PubMed  CAS  Google Scholar 

  • De Wit RH, Brabec MG. Protein synthesis by hepatic mitochondria isolated from carbon tetrachloride-exposed rats. Biochim Biophys Acta. 1985;824:256-61.

    PubMed  CAS  Google Scholar 

  • Esteve JM, Mompo J, DeLaasuncion JG, et al. Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: studies in vivo and in vitro. FASEB J. 1999;13: 1055-64.

    PubMed  CAS  Google Scholar 

  • Heminger KA, Hartson SD, Rogers J, Matta RL. Cisplatin inhibits protein synthesis in rabbit reticulocyte lysate by causing an arrest in elongation. Arch Biochem Biophys. 1997;344:200-7.

    Article  PubMed  CAS  Google Scholar 

  • Giri A. Studies on the effect of cisplatin on malignant and normal cells: preliminary investigations on cisplatin combination chemotherapy [PhD thesis]. Shillong: North-Eastern Hill University; 1995.

    Google Scholar 

  • Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol. 1999;17:409-22.

    PubMed  CAS  Google Scholar 

  • Just G, Holler E. Enhanced levels of cyclic AMP, adenosine (5')tetraphospho(5')adenosine and nucleoside 5'-triphosphates in mouse leukemia P388/D1 after treatment with cis-diamminedichloroplatinum(II). Biochem Pharmacol. 1991;42:285-91.

    Article  PubMed  CAS  Google Scholar 

  • Kim YK, Byun HS, Kim YH, Woo LS, Lee SH. Effect of cisplatin on renal function in rabbits: mechanism of reduced glucose reabsorption. Toxicol Appl Pharmacol. 1995;130: 19-26.

    Article  PubMed  CAS  Google Scholar 

  • King TE. Preparation of succinate dehydrogenase and reconstitution of succinate oxidase. In: Estabrook RW, Pullman ME, eds. Methods in enzymology. Vol. X. New York: Academic Press; 1967:322-31.

    Google Scholar 

  • Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 1998;34:1522-34.

    Article  PubMed  CAS  Google Scholar 

  • LeDoux SP, Wilson GL, Beecham EJ, Stevnsner T, Wassermannn K, Bohr VA. Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells. Carcinogenesis. 1992;13:1967-73.

    PubMed  CAS  Google Scholar 

  • Le-Quoc D, Le-Quoc K. Relationships between the NAD(P) redox state, fatty acid oxidation, and inner membrane permeability in rat liver mitochondria. Arch Biochem Biophys. 1989;273:466-78.

    Article  PubMed  CAS  Google Scholar 

  • Lewis LD, Hamseh FM, Lietman PS. Ultrastructural changes associated with reduced mitochondrial DNA and impaired mitochondrial function in the presence of 2'3'-dideoxycytidine. Antimicrob Agents Chemother. 1992;36:2061-5.

    PubMed  CAS  Google Scholar 

  • Li X, Metzger G, Filipski E, et al. Pharmacologic modulation of reduced glutathione circadian rhythms with buthionine sulfoximine: relationship with cisplatin toxicity in mice. Toxicol Appl Pharmacol. 1997;143:281-90.

    Article  PubMed  CAS  Google Scholar 

  • Lim LO, Neims AH. Mitochondrial DNA damage by bleomycin. Biochem Pharmacol. 1987;36:2769-74.

    Article  PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265-75.

    PubMed  CAS  Google Scholar 

  • Meister A. Glutathione metabolism and its selective modification. J Biol Chem. 1988;263:17205-8.

    PubMed  CAS  Google Scholar 

  • Murphy MP, Smith RAJ. Drug delivery to mitochondria: the key to mitochondrial medicine. Adv Drug Deliv Rev. 2000; 41:235-50.

    Article  PubMed  CAS  Google Scholar 

  • Nicotera P, Bellomo G, Orrenius S. Calcium-mediated mechanisms in chemically induced cell death. Annu Rev Pharmacol Toxicol. 1992;32:449-70.

    Article  PubMed  CAS  Google Scholar 

  • Niranjan BG, Bhat NK, Avadhani NG. Preferential attack of mitochondrial DNA by aflatoxin B1 during hepatocarcinogenesis. Science. 1982;215:73-5.

    PubMed  CAS  Google Scholar 

  • Olafsdottir K, Pascoe GA, Reed DJ. Mitochondrial glutathione status during Ca2+ ionophore-induced injury to isolated hepatocytes. Arch Biochem Biophys. 1988;263:226-35.

    Article  PubMed  CAS  Google Scholar 

  • Olivero OA, Semino C, Kassim A, Lopez-Larraza DM, Poirier MC. Preferential binding of cisplatin to mitochondrial DNA of Chinese hamster ovary cells. Mutat Res. 1995;346: 221-30.

    Article  PubMed  CAS  Google Scholar 

  • Olivero OA, Chang PK, Lopez-Larraza DM, Semino-Mora MC, Poirier MC. Preferential formation and decreased removal of cisplatin-DNA adducts in Chinese hamster ovary cell mitochondrial DNA as compared to nuclear DNA. Mutat Res. 1997;391:79-86.

    PubMed  CAS  Google Scholar 

  • Pessayre D, Mansouri A, Haouzi D, Fromenty B. Hepatotoxicity due to mitochondrial dysfunction. Cell Biol Toxicol. 2000;15:367-73.

    Article  Google Scholar 

  • Petit PX, LeCouer H, Zorn H, Dauget C, Mignotte B, Gougeon ML. Alteration of mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis. J Cell Biol. 1995;130:156-67.

    Article  Google Scholar 

  • Pinto AL, Lippard SJ. Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta. 1985;780:167-80.

    PubMed  CAS  Google Scholar 

  • Prasad SB, Giri A. Antitumor effect of cisplatin against murine ascites Dalton' lymphoma. Ind J Exp Biol. 1994;32:155-62.

    CAS  Google Scholar 

  • Prasad SB, Giri A. Cisplatin-induced changes in tissue calcium and potassium concentrations in tumour-bearing mice. Med Sci Res. 1999;27:459-62.

    CAS  Google Scholar 

  • Prasad SB, Giri A, Khynriam D. Studies on the chromosomes of murine Dalton' lymphoma cells and the effect of cisplatin on chromosomes of these cells and bone marrow cells in vivo. Cytologia. 1998;63:405-13.

    CAS  Google Scholar 

  • Prasad SB, Giri A, Khynriam D, Kharbangar A, Nicol BM, Lotha C. Cisplatin-mediated enzymatic changes in mice bearing ascites Dalton' lymphoma. Med Sci Res. 1999;27:723-30.

    CAS  Google Scholar 

  • Provoost AP, Molenaar JC. Changes in the glomerular filtration rate after unilateral nephrectomy in rats. Pflugers Arch. 1980;385:161-5.

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg B. Fundamental studies with cisplatin. Cancer. 1985;55:2303-16.

    Article  PubMed  CAS  Google Scholar 

  • Salazar I, Tarrago-Litvak L, Gil L, Litvak S. The effect of benzo[a]pyrene on DNA synthesis and DNA polymerase activity in rat liver mitochondria. FEBS Lett. 1982;138:45-9.

    Article  PubMed  CAS  Google Scholar 

  • Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman' reagent. Anal Biochem. 1968;25:192-205.

    Article  PubMed  CAS  Google Scholar 

  • Shan X, Jones DP, Hashmi M, Anders MW. Selective depletion of mitochondrial glutathione concentrations by (R,S)-3-hydroxy-4-pentenoate potentiates oxidative cell death. Chem Res Toxicol. 1993;6:75-81.

    Article  PubMed  CAS  Google Scholar 

  • Smaili SS, Hsu Yi-Te, Youle RJ, Russel T. Mitochondria in Ca2+ signaling and apoptosis. J Bioenerg Biomembr. 2000;32:35-46.

    Article  PubMed  CAS  Google Scholar 

  • Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991; 51:794-8.

    PubMed  CAS  Google Scholar 

  • Warburg O. On the origin of cancer cells. Science. 1956;123: 309-14.

    PubMed  CAS  Google Scholar 

  • White MT, Ayra DV, Tewari KK. Biochemical properties of neoplastic cell mitochondria. J Natl Cancer Inst. 1974;53: 553-9.

    PubMed  CAS  Google Scholar 

  • Yagi T, Hatefi Y. Thiols in oxidative phosphorylation: inhibition and energy-potentiated uncoupling by monothiol and dithiol modifiers. Biochemistry. 1984;23:2449-55.

    Article  PubMed  CAS  Google Scholar 

  • Zamble BD, Lippard SJ. Cisplatin and DNA repair in cancer chemotherapy. Trends Biochem Sci. 1995;20:435-9.

    Article  PubMed  CAS  Google Scholar 

  • Zamzami N, Marchetti P, Castedo M, et al. Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med. 1995; 181:1661-72.

    Article  PubMed  CAS  Google Scholar 

  • Zglinicki TV, Wiswedel I, Trumper L, Augustin W. Morphological changes of isolated rat liver mitochondria during Fe2+/ascorbate-induced peroxidation and the effect of thioctacid. Mech. Ageing Dev. 1991;57:233-46.

    Article  Google Scholar 

  • Zhang JG, Lindup WE. Role of calcium in cisplatin-induced cell toxicity in rat renal cortical slices. Toxicol In Vitro. 1996;10:205-9.

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Cell and Tumor Biology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong, India

    A. Kharbangar, D. Khynriam & S.B. Prasad

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  1. A. Kharbangar
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  2. D. Khynriam
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  3. S.B. Prasad
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Kharbangar, A., Khynriam, D. & Prasad, S. Effect of cisplatin on mitochondrial protein, glutathione, and succinate dehydrogenase in Dalton lymphoma-bearing mice. Cell Biol Toxicol 16, 363–373 (2000). https://doi.org/10.1023/A:1007648427024

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