Document Detail


Safety and tolerability of repeated administration of pyridoxal 2-chlorobenzoyl hydrazone in rabbits.
MedLine Citation:
PMID:  16323575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, pyridoxal 2-chlorobenzoyl hydrazone (o-108) has been identified as an effective iron chelator [Link et al., Blood 2003; 101: 4172-79]. Since chronic treatment would be necessary in its potential indications, in the present study, the safety and tolerability of this agent after repeated administration was determined. Three doses of o-108 (25, 50, 100 mg/kg, in 10% Cremophor EL) were administered intraperitoneally, once weekly, for 10 weeks to three groups (n=5 each) of Chinchilla male rabbits. The effects on biochemical, haematological and cardiovascular parameters were examined during the experiment; histopathological examination was performed at the end of the experiment. Results were compared with control (saline 2 mL/kg, n=11) and vehicle groups (10% Cremophor EL, 2 mL/kg, n=12). No premature deaths occurred; the well-being of animals was evidenced by their body weight gain, although lower gain was observed with the highest dose (100 mg/kg). Significant elevations of cardiac troponin T plasma concentrations were observed with the highest dose of o-108, but no abnormalities were found in the cardiovascular function and only minor and inconsistent changes in haematological and biochemical parameters were observed. Histopathological examinations of selected organs revealed only weak and reversible changes through all studied groups. Thus, the data from this study suggest that o-108 remains a promising drug from the standpoint of the possibility of its repeated administration and warrants further investigation.
Authors:
M Sterba; T Sim?nek; Y Mazurov?; M Adamcov?; O Popelov?; J Kaplanova; P Ponka; V Gersl
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human & experimental toxicology     Volume:  24     ISSN:  0960-3271     ISO Abbreviation:  Hum Exp Toxicol     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-02-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9004560     Medline TA:  Hum Exp Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  581-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Faculty of Medicine in Hradec Kr?lov?, Charles University in Prague, Czech Republic. sterbam@lfhk.cuni.cz
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Cell Count
Body Weight / drug effects
Dose-Response Relationship, Drug
Enzymes / blood
Hydrazones / administration & dosage,  pharmacokinetics,  toxicity*
Iron Chelating Agents / administration & dosage,  toxicity*
Male
Microscopy, Electron, Scanning
Pyridoxal / administration & dosage,  analogs & derivatives*,  pharmacokinetics,  toxicity
Rabbits
Time Factors
Tissue Distribution
Troponin T / blood
Chemical
Reg. No./Substance:
0/Enzymes; 0/Hydrazones; 0/Iron Chelating Agents; 0/Troponin T; 0/pyridoxal 2-chlorobenzoyl hydrazone; 66-72-8/Pyridoxal

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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