Influence of acetylsalicylic acid on development of radiation-induced nephropathy.
OBJECTIVE
Previous studies have demonstrated that long-term treatment with acetylsalicylic acid (ASA) can significantly reduce the renal functional impairment that develops after high doses of irradiation. The effect is hypothesized to be mediated by selective inhibition of thromboxane A2 synthesis and inhibition of platelet aggregation. The present study was undertaken to investigate this phenomenon further using more clinically relevant fractionated and re-irradiation schedules.


METHODS
Groups of mice were given bilateral renal irradiation with a series of four or 20 daily fractions of X-rays, or 10 daily fractions with a single dose of re-irradiation (0-10 Gy) after 27 weeks. Half the mice received ASA in drinking water (2.4 g x l(-1)) from 1 week before the start of irradiation and continuously throughout the follow-up period. Renal function was assessed by clearance of [51Cr]EDTA, about every 4 weeks for up to 80 weeks after the start of treatment. Histological damage in representative groups of mice was also assessed.


RESULTS
Oral administration of ASA caused inhibition of thromboxane A2 synthesis (to < 36% of controls) and a strong inhibition of platelet aggregation in whole mouse blood (ex vivo). Prolonged treatment with ASA also resulted in a small, non-significant reduction of radiation-induced renal functional damage. No reduction in histological damage was seen in the ASA treated mice.


CONCLUSIONS
Long-term oral administration of ASA gave only a modest, non-significant reduction of renal radiation injury after clinically relevant fractionated irradiation schedules.
van Kleef
E M
EM
Division of Experimental Therapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Amsterdam, The Netherlands.
Te Poele
J A
JA
Oussoren
Y G
YG
van der Wal
A
A
Dewit
L G
LG
Stewart
F A
FA
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004492:Edetic Acid; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D051379:Mice; D008809:Mice, Inbred C3H; D010974:Platelet Aggregation / Q000187:drug effects; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013997:Time Factors
D013928:Thromboxane A2; D004492:Edetic Acid; D001241:Aspirin