Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 2 (2004), No 1, p 43-49




Acute toxicity and radioprotective effects of amifostine (WR-2721) or cystamine in single whole body fission neutrons irradiated rats

Pavel Kuna, Milan Dostal, Otakar Neruda, Josef Knajfl, Pavel Petyrek, Frantisek Podzimek, Jan Severa, Vaclav Svoboda, Jan Simsa, Stanislav Spelda, Jirina Vavrova, Jindriska Hermanska, Zdenek Prouza, Pavel Pitterman, Evzen Listik, Leos Navratil, Frantisek Spurny, Frantisek Konrad, Zdena Vilasova, Renata Havrankova

Address: Pavel Kuna, Department of Radiology and Toxicology, Faculty of Health and Social Studies, Matice skolske 17, 370 01 Ceske Budejovice, Czech Republic
pavel.kuna@tiscali.cz

Received 2nd August 2003.
Revised 6th October 2003.
Published online 30th October 2003.

Full text article (pdf)

SUMMARY
The radioprotective substances amifostine (WR-2721) and cystamine were tested in rats following their parenteral administration (i.p., i.m., and i.v.). Cystamine is more toxic than amifostine in mice as well as in rats. Amifostine was less toxic after intravenous injection. The radioprotective effects of WR-2721 (160 mg.kg-1) and cystamine (40 mg.kg-1) were not significant when they were administered parenterally 15-20 mins before lethal doses of whole body fission neutron irradiation in the thermal column of reactor VVR-S and 30-days lethality served as an integral criterion of postradiation injury to the rat body. The fission neutrons spectrum was characterized by mean energy 0.9-1.0 MeV with 30-40% fluency participation of moderate (E=0.1 MeV) neutrons. The contamination with gamma rays was 22-30 %; the dose rate of whole irradiation was within 0.3 to 0.8 Gy.min-1.

KEY WORDS
Amifostine; WR-2721; cystamine; radioprotective effect; fission neutrons irradiation


REFERENCES
Ferle-Vidovic A., D. Petrovic, Z.Vidic, M. Osmak, K. Kadija: Absence of AET protection against fast neutrons: cellular effects. Radiat. Environ. Biophys. 19:197-203, 1981.

Genes V.S.: Tables of significant differences between groups of observations according to quality indicators (in Russian). Meditsina, Moscow 1964.

Kuna P.: Radioprotective effectivness of cystamine administered intramuscularly to mice (in Russian). Radiobiologya, 22, 1982:517-519.

Kuna P.: Appearance of radioprotective effect of gammaphos (WR-2721) in mice (in Czech). Čas. Lék. čes., 121, 1982a:912-914.

Kuna P.: Duration and degree of radioprotection of WR-2721 in mice following its intraperitoneal, intramuscular and subcutaneous administration. Radiobiol. Radiother. (Berlin), 24, 1983:357-364.

Kuna P.: Radioprotection of small intestine and spleen hemopoiesis by gammaphos (WR-2721) or cystamine in whole body gamma irradiated mice. Biológia (Bratislava), 39, 1983:273-282.

Kuna P.: Chemical radioprotection (in Czech). Avicenum, Praha 1985, pp. 148. (Translated into Russian: Meditsina, Moscow 1989, pp. 190).

Kuna P., M. Dostal, O. Neruda, P. Petyrek, V. Svoboda, M. Resl, Z. Prouza, J. Hermanska, F. Spurny, E. Listik, P. Pitterman, J. Knajfl, J. Simsa, S. Spelda, F. Podzimek: Radioprotective effects of gammaphos (WR-2721) and cystamine in the case of whole-body irradiation of mice by fission neutrons (in Czech). Sborn. lek. (Praha) 90:110-116, 1988.

Kuna P., C. Krajcovic: Acute toxicity and radioprotective effectiveness of gammaphos (WR-2721) in rats (in Czech). Cas. Lek. ces. 120:776-778, 1981.

Kuna P., O. Neruda, L. Navratil, J. Matzner, R. Zisková: Nuclear Terrorism. J. Appl. Biomed. 1:55-59, 2003.

Kuna P., K. Volenec, I. Vodicka, M. Dostal: Radioprotective and hemodynamic effects of WR-2721 and cystamine in rats: Time course studies. Neoplasma, 30:349-357, 1983.

Langendroff H., M.Langendorff, R. Metzner, H. Monig, K.-H. Steinbach, W. Temme, G. Tumbragel: Radiobiological investigations with fast neutrons. II. The radioprotective action of different substances on male mice. Atomkernergie 18:83-88, 1971.

Piper J.R., C.R. Stringfellow, R.D. Elliot, T.P. Johnston: S-2-(3-aminoalkylamino)ethyl dihydrogen phosphorothioates and related compounds as potential antiiradiation agents. J. Med. Chem. 12:236-243, 1969.

Pospisil M.: Pharmacological radiation protection. In: C. Baumstark-Khan et al. (eds.). Fundamentals for the assessment of risks from environmental radiation. Kluwer Academic Publishers, The Netherlands 1999, pp. 411-420.

Roth Z., M. Josifko, V. Maly, V. Trcka: Statistical methods in experimental medicine (in Czech). Státni zdravotnicke nakladatelstvi, 1962, pp. 589.

Sedlmeier H., E. Metzger, U. Jentzsch, E. Weitzenegger: Schutzeffekt von Aminoprolylamino-athylthiophosphat (WR-2721) bei Neutronen-, Gamma- oder Rontgenbestrahlung von Mausen. Strahlentherapie 157 685-691, 1981.

Sigdestad C.P., A.M. Connor, R.M. Scott: Effect of chemical protectors on the response of the intestine to roentgen or fission neutron irradiation. Acta Radiol Ther. Phys. Biol. 15:401-409, 1976.

Sigdestad C.P., D.J. Grdina, A.M. Connor, W.R. Hanson: A comparison of radioprotection from three neutron cources and 60Co by WR-2721 and WR-151327. Radiat. Res. 106:224-233, 1986.

Sigdestad C.P., A.M. Connor, C.S. Sims: Modification of neutron-induced hematopoietic effects by chemical radioprotectors. Int. J. Radiat. Oncol. Biol. Phys. 22:807-811, 1992.

Suchter L.M., M.L. Hensley, N.J. Meropol, E.P. Winer: 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: Clinical Practice Guidelines of the American society of clinical oncology. J. Clin. Oncol. 20:2895-2903, 2002.

Sverdlov A:G.: Biological effects of neutrons and chemical protection (in Russian). Nauka, Leningrad 1974, pp. 224.
CITED

0

BACK