Morphologic Change of Proximal Convoluted Tubules in Radiation-Induced Renal Injury in Rats

ABSTRACT

Experimental studies suggest that captopril plays an important preventive role in radiation induced renal injury (RRI). To elucidate the pathogenesis of RRI and effect of captopril, one subgroup was irradiated with a single dose of 9 gray (Gy) total body irradiation and another subgroup with 17 Gy local irradiation in the right kidney. Twenty-four healthy looking Sprague-Dawley rats, weighing 200~250 g, were divided into one control and three experimental group (EG)s for this study. The control group, composed of 2 rats, was maintained on stock diet and drinking tap water. EG was divided into three. EG 1 composed of two subgroups, the first subgroup, 3 rats each, was sacrificed within 12 hours after 9 Gy and 17 Gy single dose irradiation only and the second subgroup, 2 and 1 rats each, was sacrificed 8 weeks after the same doses irradiation. EG 2 composed of subgroups of 2 and 3 rats was given 500 mg/L of captopril in the drinking water after irradiating them with 9 Gy and 17 Gy and sacrificed in the 8th week. EG 3 was subdivided into four subgroups by captopril doses given, 62.5 mg/L, 125 mg/L and 250 mg/L and sacrificed 20 weeks after 9 Gy and 17 Gy irradiation. On light microscopy proximal convoluted tubules showed cytoplasmic vacuolization and focal necrosis in the subcapsular region in EG 1 sacrificed within 12 hours after 9 Gy and 17 Gy irradiation only (sham) and very mild fibrosis in juxtamedullary regions in rats sacrificed 8 weeks after irradiation. In EG 3 these changes were severely increased with additional increased fibrosis in the juxtamedullary region in the group given captopril 62.5 mg/L. On transmission electron microscopy, there were various degenerative changes of organelle. Among the captopril administered EG 2 and EG 3, rats given a high dosage revealed milder degree of damage compared to that of rats given a low dosage, and thickening of basement membrane was remarkable in rats given a low dosage. There was a reduction in tubular damage related to the captopril dosage. According to the above findings, administration of a high dose of captopril might preserve the ultrastructure in RRI and the possible mechanism of captopril was discussed.