Toxic characteristics of the synthetic lipid a derivative DT-5461 in rats and monkeys

Toxicological Sciences

Volumn 49, Issue 2, 1999, Pages 324-331

  Sagara Ishijima, Nami ^a   Furuhama, Kazuhisa ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

Disseminated intravascular coagulation (DIC); LPS; Rats; Splenomegaly; Squirrel monkeys; Synthetic lipid A derivative

Indexed keywords

1,3 DICARBOXYISOPROPYL 2 DEOXY 6 O [2 DEOXY 3 O (N DODECANOYLGLYCYL) 4 O PHOSPHONO 2 TETRADECANOYLAMINO BETA GLUCOPYRANOSYL] 3 O (N DODECANOYLGLYCYL) 2 TETRADECANOYLAMINO ALPHA GLUCOPYRANOSIDE; BACTERIUM LIPOPOLYSACCHARIDE; COMPOUND 506; DT 5461; LACTIC ACID; LIPID A DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER THERAPY; CONTROLLED STUDY; DISSEMINATED INTRAVASCULAR CLOTTING; DRUG STRUCTURE; LEUKOCYTE COUNT; MALE; NONHUMAN; PARTIAL THROMBOPLASTIN TIME; RAT; SPLENOMEGALY; THROMBOCYTE COUNT; THROMBOCYTOPENIA;

ANIMALS; DISACCHARIDES; DISSEMINATED INTRAVASCULAR COAGULATION; HYPERPLASIA; LIPID A; LIPOPOLYSACCHARIDES; MALE; RATS; RATS, SPRAGUE-DAWLEY; SAIMIRI; SPECIES SPECIFICITY; SPLENOMEGALY; SURVIVAL RATE;

ANIMALIA; BACTERIA (MICROORGANISMS); SAIMIRI; SCIURIDAE; THROMBUS;

EID: 0033038759     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/49.2.324     Document Type: Article

References (30)

1. Akimoto, T., Kumazawa, E., Jimbo, T., Joto, N., and Tohgo, A. (1994). Antitumor effect of DT-5461a, a synthetic low-toxicity lipid A analog, involves endogenous tumor necrosis factor induction subsequent to macrophage activation. Int. J. Immunopharmacol. 16, 887-893.
2. Akimoto, T., Kumazawa, E., Jimbo, T., Joto, N., and Tohgo, A. (1995). DT-5461a, an antitumor synthetic lipid A analog, causes selective blood flow reduction in tumor tissue. Anticancer Res. 15, 105-107.
3. Alcorn, J. M., Fierer, J., and Chojkier, M. (1992). The acute-phase response protects mice from D-galactosamine sensitization to endotoxin and tumor necrosis factor-α. Hepatology 15, 122-129.
4. Berczi, I., Bertók, L., and Bereznai, T. (1966). Comparative studies on the toxicity of Eschrichia coli lipopolysaccharide endotoxin in various animal species. Can. J. Microbiol. 12, 1070-1071.
5. Brown-Borg, H. M., Klemcke, H. G., and Blecha, F. (1993). Lymphocyte proliferative responses in neonatal pigs with high or low plasma cortisol concentration after stress induced by restraint. Am. J. Vet. Res. 54, 2015-2020.
6. Galanos, C., Lüderitz, O., Rietschel, E. T., and Westphal, O. (1977). Newer aspects of the chemistry and biology of bacterial lipopolysaccharides, with special reference to their lipid A compound. Biochemistry of lipids II. Int. Rev. Biochem. 14, 239-335.
7. Goto, M., Takei, Y., Kawano, S., Tsuji, S., Fukui, H., Fushimi, H., Nishimura, Y., Kashiwagi, T., Fusamoto, H., and Kamada, T. (1992). Tumor necrosis factor and endotoxicin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat. Hepatology 16, 487-493.
8. Hewett, J. A., and Roth, R. A. (1993). Hepatic and extrahepatic pathobiology of bacterial lipopolysaccharides. Pharmacol. Rev. 45, 381-411.
9. Higgins, G. M., and Anderson, R. M. (1931). Experimental pathology of the liver: I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 12, 186-202.
10. Inage, F., and Furuhama, K. (1997). Application of maximal removal rate of indocyanine green to the determination of hepatic functional mass in conscious rats. J. Vet. Med. Sci. 59, 335-340.
11. Jimbo, T., Akimoto, T., and Tohgo, A. (1995). Effect of combined administration of a synthetic low-toxicity lipid A derivative, DT-5461a, and indomethacin in various experimental tumor models of colon 26 carcinoma in mice. Cancer Immunol. Immunother. 40, 10-16.
12. Jimbo, T., Akimoto, T., and Tohgo, A. (1996). Systemic administration of a synthetic lipid A derivative, DT-5461a, reduces tumor blood flow through endogenous TNF production in hepatic cancer model of VX2 carcinoma in rabbits. Anticancer Res. 16, 359-364.
13. Joto, N., Akimoto, T., Someya, K., and Tohgo, A. (1995). Production of tumor necrosis factor induced by synthetic low-toxicity lipid A analog, DT-5461a, is mediated by LPS receptor sites and tyrosine kinase-MAP kinase signailing pathway in murine macrophages. Cell. Immunol. 160, 1-7.
14. Kateley, J. R., Nickerson, D. A., and Gengozian, N. (1977). Mitogenic response of marmoset lymphocytes: Cytokinetics and identification of responsive cells. Immunology 33, 653-662.
15. Keppler, D., Hagmann, W., Rapp, S., Denzlinger, C., and Koch, H. K. (1985). The relation of leukotrienes to liver injury. Hepatology 5, 883-891.
16. Kumazawa, E., Akimoto, T., Kita, Y., Jimbo, T., Joto, N., and Tohgo, A. (1995). Intratumoral production of tumor necrosis factor augmented by endogenous interferons results in potent antitumor effects of DT-5461, a synthetic lipid A analog. J. Immunother. Emphasis Tumor Immunol. 17, 141-150.
17. Kumazawa, E., Jimbo, T., Akimoto T., Joto, N., and Tohgo, A. (1997). Antitumor effect of DT-5461, a lipid A derivative, against human tumor xenografts is mediated by intratumoral production of tumor necrosis factor and affected by host immunosuppressive factors in nude mice. Cancer Invest. 15, 522-530.
18. Kumazawa, E., Tohgo, A., Soga, T., Kusama, T., and Osada, Y. (1992). Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine syngeneic tumor models. Cancer Immunol. Immunother. 35, 307-314.
19. Kusama, T., Soga, T., Ono, Y., Kumazawa, E., Shioya, E., Nakayama, K., Uoto, K., and Osada, Y. (1991). Synthesis and biological activities of lipid A analogs: Modification of a glycosidically bound group with chemically stable polar acidic groups and lipophilic groups on disaccharide backbone with tetradecanoyl or N-dodecanoylglycyl groups. Chem. Pharm. Bull. 39, 3244-3253.
20. Lipinski, B., Gurewich, V., and Hyde, E. (1976). Thrombin elaboration in endotoxin-induced intravascular fibrin deposition. A leukocyte dependent process distinct from systemic hypercoagulability. Thromb. Haemost. 36, 615-622.
21. Lüderitz, O., Freudenberg, M. A., Galanos, C., Lehman, V., Rietschel, E. T. H, and Shaw, D. H. (1982). Lipopolysaccharides of gram-negative bacteria. Curr. Top. Membr. Transp. 17, 79-151.
22. Lüderitz, O., Galanos, C., Lehmann, V., Nurminen, M., Rietschel, E. T., Rosenfelder, G., Simon, M., and Westphal, O. (1973). Lipid A: Chemical structure and biological activity. J. Infect. Dis. 128(suppl.), S17-S29.
23. Mizoguchi, Y., Sakagami, Y., Kuboi, H., Kobayashi, K., and Yano, I. (1988). Effects of the polysaccharide chain of lipopolysaccharide in an experimental massive hepatic cell necrosis model. Biochem. Biophy. Res. Commun. 155, 1305-1310.
24. Morrison, D. C., and Ulevitch, R. J. (1978). The effects of bacterial endotoxins on host mediation system. Am. J. Pathol. 93, 526-617.
25. Sagara, N., Furuhama, K., Kakihata, K., Nishizawa, R., and Takayama, S. (1990). Potentiation of endotoxin-induced toxicity in rats with the hypercoagulable states. J. Toxicol. Sci. 15, 219.
26. Schoendorf, T. H., Rosenberg, M., and Beller, F. K. (1971). Endotoxin-induced disseminated intravascular coagulation in nonpregnant rats: A new experimental model. Am. J. Pathol. 65, 51-58.
27. Tatsumi, M., Fujiwara, T., and Hayami, M. (1982). Blastogenic response of peripheral blood lymphocytes to mitogens in cynomolgus monkeys (Macaca fascicularis). Am. J. Primatol. 3, 111-119.
28. Tomikawa, M., Ogawa, H., and Abiko, Y. (1974). Experimental model of pulmonary thrombosis in rat. Thromb. Diath. Haemorrh. 31, 86-102.
29. Yamaguchi, F., Takahashi, Y., and Furuhama, K. (1999). Application of in vitro methods using peripheral whole blood to selecting highly susceptible individuals among common squirrel monkeys (Saimiri Sciureus) to bacterial lipopolysaccharides. Food Chem. Toxicol. 37, 117-123.
30. Yoshikawa, T., Furukawa, Y., Murakami, M., Takemura, S., and Kondo, M. (1981). Experimental model of disseminated intravascular coagulation induced by sustained infusion of endotoxin. Res. Exp. Med. (Berl.) 179, 223-228.