Toxicity of Hematoporphyrin-Coated Magnetic Ferrofluid in Rats

  • Hwang Youn-Hwan (Division of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University) ;
  • Lim Jong-Hwan (Division of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University) ;
  • Park Byung-Kwon (Division of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University) ;
  • Kim Myoung-Suk (Division of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University) ;
  • Kim Chong-Oh (Department of Materials Science and Engineering, Chungnam National University) ;
  • Yun Hyo-In (Division of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chungnam National University)
  • Published : 2006.03.01

Abstract

The purpose of this study was to investigate the toxicity of hematoporphyrin-coated magnetic ferrofluid (HP-MF) through intravenous administration in Sprague-Dawley rats. Each group was treated with either saline, or the HP-MF at 0.5, 1, 1.5, 2 and 4 ml/kg body weight (b.w.) for the observation of survival rate, clinical symptoms, laboratory values and histopathological findings. In this study, HP-MF was evaluated for the survival rates, symptoms, laboratory values and histopathological examination after treatments. The result revealed that the animals in the group of HP-MF at 2 and 4 ml/kg b.w. showed some lethality. In serum biochemistry, the levels of AST, ALT and ALP were increased in the MF and HP-MF treated groups. However, histopathological examination for the suspected organs showed no evidence of hepatotoxicity and nephrotoxicity of typical iron poisoning. Though the toxicity of HP-MF was higher than that of HP, long retention of hematoporphyrin via HP-MF provides additional benefit over conventional hematoporphyrin. HP-MF could be utilized as a potential photodynamic agent in cancer therapy. It is suggested to develop an efficient external magnetic device to attract hematoporphyrin in the target site, thereby enabling to administering a small amount of HP-MF.

Keywords

References

  1. Cairo, G., Recalcati, S., Pietrangelo, A. and Minotti, G. (2002): The iron regulatory proteins: targets and modulators of free radical reactions and oxidative damage. Free. Radic. Biol. Med., 32, 1237-1243 https://doi.org/10.1016/S0891-5849(02)00825-0
  2. Fuchs, J., Weber, S. and Kaufmann, R. (2000): Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. Free. Radic. Biol. Med., 28, 537-548 https://doi.org/10.1016/S0891-5849(99)00255-5
  3. Giebel, W., Wagner, H. and Scheibe, F. (1985): Preliminary electrophysiological data after the obliteration of cochlear blood vessels by the action of a magnetic field on circulating iron particles. Arch. Otorhinolaryngol., 242, 337-341 https://doi.org/10.1007/BF00453559
  4. Halbreich, A., Roger, J., Pons, J.N., Geldwerth, D., Silva, M.F.D., Roudier, M. and Bacri, J.C. (1998): Biomedical applications of maghemite ferrofluid. Biochimie, 80, 379-390 https://doi.org/10.1016/S0300-9084(00)80006-1
  5. Kim, J.H., Kwon, S.K. and Kim, C.O. (2002): Adhesion of photosensitizer to ferrofluids for use in photodynamic therapy. Nanotechnology, 13, 610-614 https://doi.org/10.1088/0957-4484/13/5/313
  6. Kuzensove, O.A., Brusentsov, N.A., Kuznetsov, A.A., Yurchenko, N.Y., Osipov, N.E. and Bayburtskiy, F.S. (1999): Correlation of the coagulation rates and toxicity of biocompatible ferromagnetic microparticles. J. Magn. Magn. Mater., 194, 83-89 https://doi.org/10.1016/S0304-8853(98)00569-1
  7. Lacava, L.M., Lacava, Z.G.M., Azevedo, R.B., Chaves, S.B., Garcia, V.A.P., Silva, O., Pelegrini, F., Buske, N., Gansau, C., Silva, M.F.D. and Morais, P.C. (2002): Use of magnetic resonance to study biodistribution of dextran-coated magnetic fluid intravenously administered in mice. J. Magn. Magn. Mater., 252, 367-369 https://doi.org/10.1016/S0304-8853(02)00654-6
  8. Lubbe, A.S., Bergemann, C., Brock, J. and McClure, D.G. (1999): Physiological aspects in magnetic drug-targeting. J. Magn. Magn. Mater., 194, 149-155 https://doi.org/10.1016/S0304-8853(98)00574-5
  9. Osweiler, G.D. (1996): Metals and minerals, Toxicology, Lippincott Williams & Wilkins, PA, pp. 179-212
  10. Pahernik, S.A., Dellian, M., Berr, F., Tannapfel, A., Wittekind, C. and Goetz, A.E. (1998): Distribution and pharmacokinetics of Photofrin in human bile duct cancer. J. Photochem. Photobiol. B., 47, 58-62 https://doi.org/10.1016/S1011-1344(98)00203-6
  11. Tenenbein, M. (2001): Hepatotoxicity in acute iron poisoning. J. Toxicol. Clin. Toxicol., 39, 721-726 https://doi.org/10.1081/CLT-100108513
  12. Widder, K.J., Morris, R.M., Poore, G., Howard, D.P. Jr. and Senyei, A.E. (1981): Tumor remission in Yoshida sarcomabearing rats by selective targeting of magnetic albumin microspheres containing doxorubicin. Proc. Natl. Acad. Sci. USA, 78, 579-581