Source:http://linkedlifedata.com/resource/pubmed/id/12419700
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2002-11-6
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| pubmed:abstractText |
Chloramphenicol (CAP) is haemotoxic in man, inducing two forms of toxicity. First, a commonly-occurring, dose-related, reversible bone marrow depression, which develops during treatment. Second, a rarer aplastic anaemia (AA), developing after treatment, is irreversible, and often fatal. Thiamphenicol (TAP) was developed as a replacement for CAP; however, there are no toxicological investigations in the mouse or rat on the dose-related haemotoxicity of TAP, in repeat dose gavage studies. Therefore, we have conducted a comprehensive investigation in these species, administering TAP for 7-17 days, to define haematological changes. Female BALB/c mice were gavaged with TAP, daily for 7-17 days at 400-1500 mg/kg; female Wistar Hanover rats were dosed with TAP daily at 50-375 mg/kg for 9 or 10 days. Haematological changes were studied at 1, 7 and 14 days post-dosing. In mice at day 1, TAP caused decreases in RBC, HCT and Hb; reticulocytes and platelets were reduced; changes were dose-related and reversible. Marrow cell counts were reduced; marrow was hypocellular, with erythroid depletion and progenitor cell vacuolation; the myeloid/erythroid (M:E) ratio was increased. In the rat, changes were not as clear-cut; there was anaemia with indications of reduced reticulocyte and platelet counts, and evidence of decreased neutrophils and lymphocytes. Marrow erythroid cells were decreased, precursor cells vacuolated, and the M:E ratio increased. We conclude that TAP induced haematological changes in the mouse and rat, parallelling the dose-dependent, reversible marrow depression reported in man; TAP is more haemotoxic in the rat than in the mouse.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0278-6915
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
40
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1849-61
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12419700-Anemia, Aplastic,
pubmed-meshheading:12419700-Animals,
pubmed-meshheading:12419700-Anti-Bacterial Agents,
pubmed-meshheading:12419700-Apoptosis,
pubmed-meshheading:12419700-Blood Cell Count,
pubmed-meshheading:12419700-Blood Chemical Analysis,
pubmed-meshheading:12419700-Dose-Response Relationship, Drug,
pubmed-meshheading:12419700-Female,
pubmed-meshheading:12419700-Hematocrit,
pubmed-meshheading:12419700-Hematopoietic Stem Cells,
pubmed-meshheading:12419700-Hemoglobins,
pubmed-meshheading:12419700-Mice,
pubmed-meshheading:12419700-Mice, Inbred BALB C,
pubmed-meshheading:12419700-Platelet Count,
pubmed-meshheading:12419700-Random Allocation,
pubmed-meshheading:12419700-Rats,
pubmed-meshheading:12419700-Rats, Wistar,
pubmed-meshheading:12419700-Reticulocytes,
pubmed-meshheading:12419700-Species Specificity,
pubmed-meshheading:12419700-Thiamphenicol
|
| pubmed:year |
2002
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| pubmed:articleTitle |
Haemotoxicity of thiamphenicol in the BALB/c mouse and Wistar Hanover rat.
|
| pubmed:affiliation |
Centre for Toxicology, Department of Pharmacology, The School of Pharmacy, University of London, 29/39 Brunswick Square, UK. john.turton@ulsop.ac.uk
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|