Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antileishmanial potency of doxorubicin conjugated to mannose-human serum albumin (man-HSA) was tested in experimental visceral leishmaniasis. Conjugation of doxorubicin did not decrease the affinity of the neoglycoprotein for the macrophage mannose receptor. Conjugated doxorubicin eliminated intracellular amastigotes of Leishmania donovani in peritoneal macrophages almost 12.5 times more efficiently than did the free drug and greatly reduced and possibly eliminated splenic intracellular parasites in four consecutive dosages at 5 micrograms/kg/day for 45 days. Free drug at a similar dose had little effect. The leishmanicidal effect of doxorubicin conjugate can be prevented by competitive inhibitors such as man-HSA or mannan and inhibitors of receptor-mediated endocytosis such as colchicine and monensin. These results not only indicate the potential of doxorubicin as an effective chemotherapeutic agent for leishmaniasis but also establish the use of mannosylated neoglycoprotein as a drug carrier in the therapy of macrophage-associated diseases.
 ...
PMID:Macrophage-directed delivery of doxorubicin conjugated to neoglycoprotein using leishmaniasis as the model disease. 837 46

Active targeting of muramyl dipeptide (MDP) to macrophages was studied by conjugation with the neoglycoprotein, mannosyl human serum albumin (mannose-HSA) using visceral leishmaniasis as the model macrophage disease. Conjugation did not decrease the affinity of the neoglycoprotein for macrophage mannose receptor. Mannose-HSA-MDP was 50 times more efficient than free MDP in inhibiting the growth of Leishmania donovani inside peritoneal macrophages. Moreover, in a 60-day murine model of visceral leishmaniasis, 95% of the spleen parasite burden was reduced by mannose-HSA-MDP at a dose of 0.5 mg/kg/day given for 4 days. Free MDP at a similar dose had very little effect. In vitro exposure of MDP caused enhanced generation of O2- by macrophages, whereas generation of nitric oxide (NO) was not induced. The elevated antileishmanial activity of MDP-treated macrophages in culture was abrogated by O2- scavengers. In contrast, considerably enhanced amounts of NO and O2- were generated from macrophages of mannose-HSA-MDP-treated animals, and their splenocytes secreted soluble factors providing all the signals required for the induction of NO biosynthesis. The increase in NO production was paralleled by a concomitant increase in antileishmanial activity, which was reversed by NO synthesis inhibitors. Splenocyte supernatants treated with anti-IFN-gamma or anti-TNF-alpha Abs suppressed inducible NO generation by macrophages. Moreover, i.v. administration of anti-IFN-gamma and anti-TNF-alpha along with mannose-HSA-MDP greatly reduced protection against L. donovani infection. Neoglycoprotein-conjugated MDP, therefore, activated mouse macrophages in vivo to kill L. donovani, and this may depend on the physiologic generation of NO induced by IFN-gamma and TNF-alpha.
 ...
PMID:Protective effect of neoglycoprotein-conjugated muramyl dipeptide against Leishmania donovani infection: the role of cytokines. 916 56