Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-6-17
pubmed:abstractText
A major toxic effect of the chemotherapeutic agents paclitaxel and cisplatin is peripheral neuropathy. We report the use of a rat model of cytotoxic neuropathy to evaluate the role of glutamate as a possible neuroprotectant for these two drugs. Neuropathy was manifest as gait disturbance in 100% of paclitaxel treated animals after 2 weeks and 100% of cisplatin treated animals after 8 weeks. Significant elevations of mean tail-flick threshold, a measure of sensory impairment, were observed in animals treated with both cytotoxics. Impaired rota-rod performance was observed in both light and dark with paclitaxel, indicating motor neuropathy. There was a trend towards impairment in the dark for cisplatin, suggesting proprioceptive loss. In cytotoxic treated animals supplemented with oral sodium glutamate (approx. 500 mg/kg/day in drinking water) from 24 h before chemotherapy, there was a significant delay in time to onset of gait disturbance allowing significantly higher mean doses to be tolerated. Mean tail-flick and rota-rod scores were unchanged from baseline for both drugs. Glutamate therefore protected against both sensory and motor neuropathy. Similar doses of glutamate did not impair the cytotoxic efficacy of paclitaxel or cisplatin against a transplantable rat mammary adenocarcinoma grown subcutaneously in rats. Our findings suggest that glutamate warrants clinical trial as a neuroprotectant in patients receiving paclitaxel or cisplatin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0167-594X
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
107-16
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Amelioration of experimental cisplatin and paclitaxel neuropathy with glutamate.
pubmed:affiliation
Department of Clinical Oncology, Royal North Shore Hospital, Sydney, Australia. franb@med.usyd.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't