Abstract
The bladders of anaesthetised mice were illuminated with red laser light (630 nm) at intervals of 1 day to 4 weeks after i.p. administration of Photofrin. Light was delivered intravesically by inserting a fibre optic, with a diffusing bulb tip, into the centre of fluid filled bladders. A single light dose of 11.3 J cm-2 applies 1 day after 10 mg kg-1 Photofrin caused a severe acute response, with increased urination frequency (five to seven times control) and hematuria. Recovery was good, however, and by 10 weeks only a mild (approximately two-fold) increase in frequency remained. There was no reduction in the amount of acute bladder damage or in the rate of healing when the interval between Photofrin and light was increased from 1 to 7 days but a 2 to 3 week interval lead to a significant reduction in damage. For an interval of 4 weeks there was only a mild (less than two-fold) increase in urination frequency during the first week. A drug dose of 2.5 mg kg-1 given 1 day before illumination caused transient haematuria but no increase in urination frequency. Doses of 5, 7.5 or 10 mg kg-1 all caused photosensitisation and the amount of bladder damage was drug dose dependent. The bladder seems to be well able to recover from severe acute damage induced by PDT. Occasional incidences of pyelonephritis were seen, however, suggesting that urinary tract infection during the acute period may lead to permanent renal damage.
Highlights
The mean Frequency Index (FI) for control animals over the 52 week testing period was 5.1 spots ml-' ( ± 2.2, 1 s.d.), i.e. a mean of 2.7 ml urine excreted as 13.8 spots during the 24 h test period
A total of four separate experiments contributed to the results described here and for each experiment a group of six to nine mice were treated with a standard drug dose of 10mgkg-' at 24h before 11.3 J cm2. This dosing schedule produced a large increase in Fl in all mice during the first week after treatment
The frequency response of mice treated in the four separate experiments was generally very similar, recovery from 18 to 38 weeks was slightly slower in experiments 1 and 4
Summary
The purpose of this study was to determine the influence of sensitiser dose (Photofrin) and time of administration on the extent of damage and recovery in normal bladder, using a mouse model
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