Skip to main content
Log in

Free radical scavengers suppress the accumulation of platinum in the cerebral cortex

  • Accelerated Article
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

We investigated whether free radical scavengers and antioxidants inhibit the accumulation of platinum (Pt) in the cerebral cortex. Pt was detected in the cerebral cortex of mice afters administration of cisplatin and exposure to short-term hypoxia. When mice were treated with either allopurinol (20 mg/kg) or catalase (100 mg/kg) before cisplatin administration and low oxygen exposure, Pt was not detected in the cerebral cortex. However, Pt was detected in the cerebral cortex of mice pretreated with either a low dosage of allopurinol or heat-denatured catalase. Furthermore, Pt was detected in the cerebral cortex of mice preadministered vitamin C, vitamin E, or deferoxamine. Lipid peroxide levels in the cerebral cortex increased 10 min after the treatment of hypoxia, and peaked 30 min after the treatment. These results suggested that short-term hypoxia produces free radicals, which allows Pt to pass through the blood-brain barrier and accumulate in the cerebral cortex, and that the production of free radicals is reduced by the administration of either allopurinol or catalase, which prevents Pt from passing through the barrier.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. W. M. Pardridge, Recent advances in blood-brain barrier transport,Ann. Ver. Pharmacol. Toxicol. 28, 25–39 (1988).

    Article  CAS  Google Scholar 

  2. S. I. Rapoport, M. Hori, and I. Klatzo, Reversible osmotic opening of the blood-brain barrier,Science 173, 1026–1028 (1971).

    Article  PubMed  CAS  Google Scholar 

  3. R. Suzuki, T. Yamaguchi, T. Kirino, F. Orzi, and I. Klatzo, The effects of 5-minute ischemia in mongolian gerbils: I. Blood-brain barrier, cerebral blood flow, and local cerebral glucose utilization changes,Acta Neuropathol. 60, 207–216 (1983).

    Article  PubMed  CAS  Google Scholar 

  4. N. Saito, C. Chang, K. Kawai, F. Joo, T. S. Nowak Jr., J. Ikeda, G. Nagashima, C. Ruetzler, J. Lohr, M. Spatz, and I. Klatzo, Role of neuroexcitation in development of blood-brain barrier and oedematous changes following cerebral ischaemia and traumatic brain injury.Acta Neurochir. Suppl. 51, 186–188 (1990).

    CAS  Google Scholar 

  5. A. Patt, R. B. Rutherford, W. H. Pearce, and J. E. Repine, Cerebral ischemia-reperfusion injury in the gerbil,J. Surg. Res. 42, 462–466 (1987).

    Article  PubMed  CAS  Google Scholar 

  6. T. Minami, M. Ichii, and Y. Okazaki, Detection of platinum in the brain of mice treated with cisplatin and subjected to short-term hypoxia.J. Pharm. Pharmacol. 48, 505–509 (1996).

    PubMed  CAS  Google Scholar 

  7. C. Palmer, R. C. Vannucci, and J. Towfighis, Reduction of perinatal hypoxic-ischemic brain damage with allopurinol,Pediat. Res. 27, 332–336 (1990).

    Article  PubMed  CAS  Google Scholar 

  8. C. Palmer, J. Towfighi, R. L. Roberts, and D. F. Heitjan, Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats,Pediat. Res. 33, 405–411 (1993).

    Article  PubMed  CAS  Google Scholar 

  9. M. Yamamoto, T. Shima, T. Uozumi, T. Sogabe, K. Yamada, and T. Kawasaki, A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of α-tocopherol administration.Stroke 14, 977–982 (1983).

    PubMed  CAS  Google Scholar 

  10. E. S. Flamm, H. B. Demopoulos, M. L. Seligman, R. G. Poser, and J. Ransohoff, Free radicals in cerebral ischemia,Stroke 9, 445–447 (1978).

    PubMed  CAS  Google Scholar 

  11. W. H. Gispen, P. Schotman, and E. R. De Kloet, Brain RNA and hypophysectomy; A topographical study,Neuroendocrinol 9, 285–296 (1972).

    CAS  Google Scholar 

  12. T. Minami, M. Ichii, and Y. Okazaki, Comparison of three different methods for measurement at tissue platinum level,Biol. Trace Elem. Res. 48, 37–44 (1995).

    Article  PubMed  CAS  Google Scholar 

  13. K. Yagi, A simple fluorometric assay for lipoperoxide in blood plasma,Biochem. Med. 15, 212–216 (1976).

    Article  PubMed  CAS  Google Scholar 

  14. J. M. Hill, E. Loeb, A. Maclellan, M. O. Hill, A. Khan, and J. J. King, Clinical studies of platinum coordination compounds in the treatment of various malignant diseases,Cancer Chemother. Rep. 59, 647–659 (1975).

    PubMed  CAS  Google Scholar 

  15. H. R. Brady, M. L. Zeidel, B. C. Kone, G. Giebisch, and S. R. Ullans, Differential actions of cisplatin on renal proximal tubule and inner medullary collecting duct cells,J. Pharm. Exper. Ther. 265, 1421–1428 (1993).

    CAS  Google Scholar 

  16. S. W. Thompson, L. E. Davis, M. Kornfeld, R. D. Hilgers, and J. C. Standefer, Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies,Cancer 54, 1269–1275 (1984).

    Article  PubMed  CAS  Google Scholar 

  17. R. W. Gregg, J. M. Molepo, V. J. A. Monpetit, N. Z. Mikael, D. Redmonds, M. Gadia, and D. J. Stewart, Cisplatin neurotoxicity: The relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity,J. Clin. Oncol. 10, 795–803 (1992).

    PubMed  CAS  Google Scholar 

  18. J. Z. Ginos, A. J. L. Cooper, V. Dhawan, J. C. K. Lai, S. C. Strother, N. Alcock, and D. A. Rotternberg, [13N] Cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors,J. Nucl. Med. 28, 1844–1852 (1987).

    PubMed  CAS  Google Scholar 

  19. J. T. Coyle and P. Puttfaarcken, Oxidative stress, glutamate, and neurodegenerative disorders,Science 262, 689–695 (1993).

    Article  PubMed  CAS  Google Scholar 

  20. J. R. Zhang, P. K. Andrus, and E. D. Hall, Age-related regional changes in hydroxyl radical stress and antioxidants in gerbil brain,J. Neurochems. 61, 1640–1647 (1993).

    Article  CAS  Google Scholar 

  21. A. J. L. Cooper, W. A. Pulsinelli, and T. E. Duffy, Glutathione and ascorbate during ischemia and postischemic reperfusion in rat brain,J. Neurochem. 35, 1242–1245 (1980).

    Article  PubMed  CAS  Google Scholar 

  22. T. K. Aalto and K. O. Raivio, Nucleotide depletion to reactive oxygen metabolites in endothelial cells: Effects of antioxidants and 3-aminobenzamide,Pediatr. Res. 34, 572–576 (1993).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Minami, T., Ichii, M., Okazaki, J. et al. Free radical scavengers suppress the accumulation of platinum in the cerebral cortex. Biol Trace Elem Res 55, 1–7 (1996). https://doi.org/10.1007/BF02784163

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02784163

Index Entries

Navigation