Effects of nitric oxide manipulation on the disposition of platinum in an experimental glioma model.
Rodents with striatal C6 glioma were given carboplatin (65 mg kg(-1) in a 10 mg ml(-1) solution, i.v.) after pretreatment with the NO modulating agents 3-morpholinosydnonimine (SIN-1), NG-nitro-L-arginine methyl ester (L-NAME), bradykinin or dexamethasone, to determine whether platinum disposition in the glioma and normal brain was altered. There was no significant change in mean glioma platinum disposition after 3 days of dexamethasone (32+/-9.7 microg/g). Treatment with SIN-1 (45.1+/-14.2 microg/g), L-NAME (42.9+/-4.9 microg/g) and bradykinin (45.7+/-11.3 microg/g) all resulted in increased tumour platinum concentration compared with controls (29+/-5.5 microg/g) but these results were not statistically significant. Dexamethasone significantly (p < 0.05) reduced the platinum concentration in normal brain but the other agents had no effect. Although glioma platinum concentration could be increased by some agents that alter tissue NO levels, the patterns of response were unpredictable and the magnitude (approximately 50%) of the increased platinum disposition is unlikely to be biologically significant.
Malcolm
G P
GP
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, UK.
Jodrell
D I
DI
MacLellan
A
A
Swaroop
G R
GR
Kelly
P A
PA
Whittle
I R
IR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D017072:Neostriatum / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010984:Platinum / Q000097:blood / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D010984:Platinum; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D001920:Bradykinin