Amelioration of radiation nephropathy by acetylsalicylic acid.
This investigation was carried out to assess the amelioration by two antithrombotic drugs of radiation nephropathy in mice. Mouse kidneys were given split-dose irradiation to total doses between 17 and 22 Gy. A first group of animals was given acetylsalicylic acid (ASA) in drinking water, a second received daltroban, a thromboxane A2/prostaglandin H2 receptor antagonist, and a third received normal tap water, serving as a control. Both antithrombotic drugs were started 1 week prior to the irradiation and were given throughout the whole follow-up period. Renal function was assessed every 4 weeks from 18 weeks after the start of irradiation onwards by measuring the [51Cr] EDTA retention and haematocrit. The dose of ASA (600 mg/kg/day) caused an inhibition of thromboxane A2 and prostacyclin biosynthesis to 19 +/- 10 (mean +/- SEM) and 85 +/- 22%, respectively, as assessed by the excretion of their urinary metabolites. A significant sparing effect on the renal function after irradiation was observed in the ASA-treated animals. Using the latency time to reach 4% residual plasma activity of [51Cr] EDTA, a dose-modifying factor of 1.19 was calculated. No effect was seen with daltroban (10 mg/kg/day). Histopathological analysis of the kidneys at 12 months after irradiation demonstrated a substantially lower level of damage in the ASA-treated mice compared with daltroban-treated and radiation-only animals. These data indicate that long-term treatment with ASA is effective in reducing renal functional impairment after irradiation.
Verheij
M
M
Department of Radiotherapy, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis, Amsterdam.
Stewart
F A
FA
Oussoren
Y
Y
Weening
J J
JJ
Dewit
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D005260:Female; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D007677:Kidney Function Tests; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D013929:Thromboxane B2 / Q000652:urine; D014965:X-Rays
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin