Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Daunorubicin is a highly potent trypanocide in-vitro but is inactive in-vivo. When daunorubicin is conjugated to bovine serum albumin or horse spleen ferritin using Schiffs base linkages, the complex is trypanocidal in-vitro and in-vivo. We have developed novel analytical methods, using HPLC with fluorimetric detection, for the quantitation of daunorubicin and doxorubicin in biological samples, either as unconjugated drug, or when covalently linked to macromolecules or particles. Ferritin-daunorubicin conjugate (25 mg kg-1) was administered intraperitoneally to mice infected with monomorphic Trypanosoma brucei rhodesiense; peak plasma levels occurred after 1.5 h, and were 5 times higher than those resulting from administration of an equivalent amount of unconjugated daunorubicin. Plasma levels then declined rapidly (t1/2 for 1-6 h period was 0.58 and 0.86 h respectively for conjugated and unconjugated daunorubicin). However, higher plasma levels were seen 24 h after treatment, suggesting the distribution profile of daunorubicin when conjugated to ferritin is multiphasic with resultant high levels of daunorubicin obtained for a prolonged time period.
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PMID:Method for analysis, and distribution profile, of covalently-linked ferritin-daunorubicin conjugate in the blood of trypanosome-infected mice. 135 Jun 28

Rat-liver microsomes and NADPH could reduce Adriamycin, epirubicin and daunorubicin to their free radical forms, which enhanced peroxidation of microsomal lipids less than 2-fold in air but 3- to 5-fold at a pO2 of 4 mmHg. Mitoxantrone was not reduced by microsomes and had no effect on microsomal peroxidation. Daunorubicin caused more lipid peroxidation than similar concentrations of either Adriamycin or epirubicin, which were equally efficient. In each case peroxidation was iron-dependent and could be catalysed by ferritin. The antioxidants beta-carotene and alpha-tocopherol inhibited lipid peroxidation at low or high pO2. The dose-for-dose difference in the cardiotoxicity of epirubicin compared with Adriamycin is not explained by its effect on microsomal lipid peroxidation. However, the lower incidence of cardiotoxicity with mitoxantrone may be a consequence of its inability to form free radical species and promote lipid peroxidation.
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PMID:Microsomal lipid peroxidation induced by adriamycin, epirubicin, daunorubicin and mitoxantrone: a comparative study. 254 12

The nucleus (but not the kinetoplast) of Trypanosoma rhodesiense is the principal target for trypanocidal attack by Daunomycin in vitro and Daunomycin-protein conjugates in vivo; free Daunomycin is inactive in vivo. Nucleolar segregation and abnormal distribution of heterochromatin occur after drug treatment as in tumour cells. Other abnormal changes include formation of cytoplasmic clefts and autophagic vacuoles, increased prominence of the tubular collection system, and exocytotic vesicle production. Large masses of ferritin accumulate in white cells after treatment with the drug-ferritin conjugate but no ferritin was detectable in trypanosomes.
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PMID:Effects of Daunomycin and Daunomycin-protein conjugates on the ultrastructure of Trypanosoma rhodesiense. 666 10