Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지

Protective Effect of Aminoglycosides and Their Combinations Against 2-Chloroethylethyl Sulfide Exposure

  • Kim, Yun-Bae (Biomedical Assessment Lab.Agency for Defense Development) ;
  • Hur, Gyeung-Haeng (Biomedical Assessment Lab Agency for Defense Development) ;
  • Choi, Dae-Sung (Biomedical Assessment Lab. Agency for Defense Development) ;
  • Shin, SungHo (Biomedical Assessment Lab Agency for Defense Development) ;
  • Cha, Seung-Hee (Biomedical Assessment Lab. Agency for Defense Development) ;
  • Park,Yong-Keun (Department of Biology, Korea University) ;
  • Sok, Dai-Eun (College of Pharmacy, Chungnam National University)
  • Published : 1997.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Exposure of splenocytes to 2-chloroethylethyl sulfide (CEES) resulted in the cell death, and the cytotoxicity of CEES was prevented by inhibitors of lysosomal hydrolases. Therefore, it has been postulated that the cytotoxicity of CEES may be partially due to the lysosomal labilization. This study, based on this mechanism, was undertaken to determine whether aminoglycoside antibiotics as inhibitors of lysosomal phospholipases and their combinations with other lysosome stabilizers can be useful as a treatment to reduce the CEES toxicity in mice. 2-Chloroethylethyl sulfide (20 mg/kg body weight) was injected ip into female ICR mice, and candidate compounds were administered ip before or after the CEES challenge. Kanamycin (40 mg/kg body weight) as effective as deferoxamine (100 mg/kg body weight) enhanced the survival rate after 5 days of intoxication from 10% of control to 50 - 60%. The most effective was found to be the combination of kanamycin, cycloheximide, deferoxamine and dextrose showing an almost full protection against 2LD50 of CEES. Consistent with the protection of the CEES toxicity, the decrease of body weight in mice intoxicated with CEES was effectively prevented by kanamycin or its combinations. It is suggested that kanamycin or its combination (kanamycin, cycloheximide, deferoxamine and dextrose) would be one of effective antidotes against the CEES poisoning in mice.

Keywords

References

  1. Supplement to Proceedings of the Third International Symposium on Protection Against Chemical Warfare Agents Protective effects of N-acetylcysteine and sodium thiosulfate on sulfur mustard poisoning in mice Balali-Mood, M.;National Defence Research Establishment(ed.)
  2. Korean Biochem. J. v.27 Protective effect of poly(ADP-ribose) polymerase inhibitors on 2-chloroethylethyl sulfide-induced cytotoxicity in murine lymphocytes Choi, D.-S.;Park, Y.-K.;Kim, Y.-B.;Hur, G.-H.;Sok, D.-E.
  3. J. Biochem. Mol. Biol. v.28 An additional mechanism for the cytotoxicity of 2-chloroethyethyl sulfide in spleen lymphocytes; lysosomal labilization Choi, D.-S.;Shin, S.-H.;Kim, Y.-B.;Cha, S.-H.;Sok, D.-E.
  4. Cell Biol. Toxicol. v.9 Effects of specific inhibitors of cellular functions on sulfur mustard-induced cell death Clayson, E.;Kelly, S.A.;Meier, H.L.
  5. Trends Pharmacol. Sci. v.18 Reactive species and their accumulation on radical damaged proteins Dean, R.T.;Gieseg, S.;Davies, M.J.
  6. Toxicology v.72 Free radical-mediated lung response to the monofunctional sulfur mustard butyl 2-chloroethyl sulfide after subcutaneous injection Elsayed, N.M.;Omaye, S.T.;Klain, G.J.;Korte, D.W., Jr.
  7. Toxicology v.58 Responses of mouse brain to a singel subcutaneous injection of the monofunctional sulfur mustard, butyl 2-chloroethyl sulfide (BCS) Elsayed, N.M.;Omaye, S.T.;Klain, G.J.;Inase, J.L.;Hahlberg, E.T.;Wheeler, C.R.;Korte, D.W., Jr.
  8. Proc. Soc. Exp. Biol. Med. v.115 Reversal of nitrogen mustard intoxication by anti-histamines Field, J.B.;Mireles, A.;Dolendo, E.C.;Ershoff, B.H.
  9. Principles and Methods of Toxicology Statistics for toxicologists Gad, S.C.;Weil, C.S.;Hayes, W.(Ed.)
  10. Toxicol. in Vitro v.6 In vitro toxicological lesions of bis(betachloroethyl)sulfide (BCES) on human epidermis reconstituted in culture. Morphological alterations and biochemical depletion of glutathione Gentilhomme, E.;Neveux, Y.;Hua, A.;Thiriot, C.;Faure, M.;Thivolet, J.
  11. J. Appl. Toxicol. v.13 Early cytotoxic effects induced by bis-chloroethyl sulphide (sulfur mustard_: $[Ca^{2+}]$, rise and time-dependent inhibition of B77 fibroblast serum response Hua, A.;Daniel, R.;Jasseron, M.P.;Thiriot, C.
  12. Biochim. Biophys. Acta v.676 Inhibition of hepatocyte protein degradation by methylaminopurines and inhibitors of protein synthesis Kovacs, A.L.;Seglen, P.O.
  13. Biochem. Pharmacol. v.34 Cellular pharmacology of deferrioxamine B and derivatives in cultured rat hepatocytes in relation to iron mobilization Laub, R.;Schneider, Y.-J.;Octave, J.-N.;Trouet, A.;Crichton, R.R.
  14. Toxicol. Appl. Pharmacol. v.113 The determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2'-dichlorodiethyl sulfide (Sulfur mustard, HD) Meier, H.L.;Johnson, J.B.
  15. Toxicol. Appl. Pharmacol. v.107 Effects of nicotinamide on biochemical changes and microblistering induced by sulfur mustard in human skin organ cultures Mol, M.A.E.;Vries, R.;Kluivers, A.W.
  16. J. Clin. Invest. v.88 Alterations in the structure, physicochemical properties, and pH of hepatocyte lysosomes in experimental iron over-load Myers, B.M.;Prendergast, F.G.;Holman, R.;Kuntz, S.M.;LaRusso, N.F.
  17. Medical Defense against Mustard Gas: Toxic Mechanisms and Pharmacological Implications Papirmeister, B.;Feister, A.J.;Robinson, S.I.;Ford, R.D.
  18. Fund. Appl. Toxicol. v.5 Molecular basis for mustard-induced vesication Papirmeister, B.;Gross, C.L.;Meier, H.L.;Petrali, J.P.;Johnson, J.B.
  19. Toxicol. Appl. Pharmacol. v.131 Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane Ray, R.;Legere, R.H.;Majerus, B.J.;Petrali, J.P.
  20. Toxicol. Appl. Pharmacol. v.70 Inhibitory effect of Fusarium T2-Toxin on lymphoid DNA and protein synthesis Rosenberg, Y.;Lafrage-Frayssinet, C.
  21. Mol. Pharmacol. v.37 Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress Sakaida, I.;Kyle, M.E.;Farber, J.L.
  22. Chem.-Biol. Interact. v.97 The release of arylsulfatase from liver lysosomes exposed to 2-chloroethylethyl sulfide Shin, S.;Choi, D.-S.;Kim, Y.-B.;Cha, S.-H.;Sok, D.-E.
  23. Fd Chem. Toxicol. v.33 Protection by lysosomal hydrolase inhibitors against cytotoxicity of 2-chloroethylethyl sulfide Sok, D.-E.;Choi, D.-S.;Park, Y.-K.;Kim, Y.-B.;Cha, S.-H.
  24. Def. Sci. J. v.44 Therapeutic efficacy of saline and glucose-saline against dermally applied sulphur mustard intoxication in mice Sugendran, K.;Jeevaratnam, K.;Vijayaraghavan, R.;Das Gupta, S.
  25. Fund. Appl. Toxicol. v.5 The protective effect of different drugs in rats poisoned by sulfur and nitrogen mustards Vojvodic, V.;Milosavljevic, Z.;Boskovic, B.;Bojanic, N.
  26. Biochem. Biophys. Res. Comm. v.124 Enhanced lysosomal phospholipid degradation and lysophospholipid production due to free radicals Weglicki, W.B.;Dickens, B.F.;Mak, I.T.
  27. Cancer Res. v.38 Effect of cycloheximide on the bone marrow toxicity of nitrogen mustard Weissberg, J.B.;Herion, J.C.;Walker, R.I.;Palmer, J.G.
  28. Toxicology v.69 Dermal intoxication of mice with bis(2-chloroethyl)sulphide and the protective effect of flavonoids Vijayaraghavan, R.;Sugendran, K.;Pant, S.C.;Husain, K.;Malhotra, R.C.