Amelioration of radiation nephropathy in rats by postirradiation treatment with dexamethasone and/or captopril.
Dexamethasone (DEX) and captopril are effective drugs in the treatment of radiation nephropathy in experimental animals. The aim of the present study was to determine the relative effectiveness of the two drugs and to see if their combination is more effective than either drug alone. For this purpose both kidneys of 143 rats were exposed surgically and irradiated with 13-20 Gy gamma rays. The surrounding tissues, with the exception of a segment of lumbar cord, were shielded. Each group had free access to acidified drinking water containing either DEX (94 micrograms/l), captopril (500 mg/l), DEX (94 micrograms/l) + captopril (500 mg/l) or drug-free water. Dexamethasone treatment was stopped after 90 days, but animals continued to receive captopril until death. At approximately monthly intervals the animals were weighed and renal function (PUN, hematocrit, 51Cr-EDTA retention) was measured. A side effect of treatment with DEX and DEX+captopril was a reduced increase in body weight. Paralysis of the hind limbs developed in nine animals that received captopril and/or DEX treatment. The classical histological lesions associated with radiation myelopathy were not evident in these paretic rats. It is therefore suggested that paralysis may be attributed in part to drug-induced neurotoxicity in animals with impaired renal clearance. Macroscopically and histologically, nearly all the animals that survived more than 400 days had evidence of renal tumor development. Dexamethasone and/or captopril appear to selectively ameliorate glomerular compared to tubular damage, based on histological findings. All three experimental treatments delayed but did not stop the progression of lethal renal injury as measured by kidney function tests and survival time. Median survival times for nontreated and captopril-, DEX- and DEX+captopril-treated animals exposed to 14.5 to 19.0 Gy kidney irradiation were 175, 242, 261 and 395 days, respectively. The combination of captopril and DEX appears to be at least additive in that the therapeutic effect is equal to or greater than the sum of the therapeutic effect of the individual drugs. Dexamethasone appears to be as effective as or more effective than captopril in delaying renal failure.
Geraci
J P
JP
Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle 98195, USA.
Sun
M C
MC
Mariano
M S
MS
D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D007668:Kidney / Q000528:radiation effects*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats
D003907:Dexamethasone; D002216:Captopril