- Reducing Effect of Angiotensin-1 Converting Enzyme Inhibitor (Captopril) in Fibrosis of Radiation Induced Lung Injury.
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Kun Young Kwon, Hae Ra Jung, Sun Young Kwon, Jin Hee Kim, Ok Bae Kim
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Korean J Pathol. 2004;38(3):145-156.
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 Abstract
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- BACKGROUND
The captopril reduces radiation induced lung injury and fibrosis. We designed a study to evaluate the antifibrogenic effect of Captopril in radiation induced lung injury.
METHODS
Fifty Sprague-Dawley rats were divided into radiation group (I) (n=30) and radiation plus captopril group (II) (n=15). The rats were sacrificed at 12 hours and 11 weeks after radiation. We examined light microscopic, immunohistochemical and electron microscopic features in each groups.
RESULTS
In Group I, the lungs showed acute lung injury at 12 h. The lungs showed patchy fibrosis with collagen deposits at 11 weeks. The severity of the alveolar injury and fibrosis was correlated with radiation doses. The Group II showed less severe lung fibrosis than Group I. The mean numbers of mast cells and myofibroblasts of Group II were lower than Group I (p< 0.05). The TNF-alpha and TGF-beta were higher expressed according to radiation doses in Group I, and less prominent in Group II. Ultrastructurally, the alveolar cell injury and fibrosis were less severe in Group II. The TUNEL stains showed higher expressions according to radiation doses in Group I, and expressed in Group II.
CONCLUSIONS
The captopril decreases the number of mast cells and myofibroblasts, reduces collagen deposition and apoptosis of alveolar cells in rat lungs after radiation, and so reduces the degree of pulmonary injury and fibrosis.
- Protective Effects of Captopril in Radiation-Induced Renal Injury in Rats.
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Ji Yeon Bae, Eun Sook Chang, Ok Bae Kim
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Korean J Pathol. 2000;34(3):214-224.
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Abstract
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- The angiotensin I converting enzyme inhibitor (Captopril) has recently been studied extensively in various experimental models of radiation injury and has proven its protective effects in various organs, such as the lungs, gastrointestinal tract, and kidneys. Twenty-three Sprague-Dawley rats were divided into experimental and control group. The experimental group was divided into two large groups: the first one received a single dose of 18 Gy irradiation from an electron beam on the local field of the kidney region only, and the second group received captopril per oral continuously after the same doses of irradiation. The second experimental group was divided into four subgroups by captopril doses: 62.5 mg/l, 125 mg/l, 250 mg/l, and 500 mg/l, respectively.
On light and electron microscopy, the kidneys of the irradiated rats with no captopril treatment showed diffuse glomerular contraction, congestion with occlusion and focal necrosis of the endothelial, and mesangial cells. The tubules showed ballooning degeneration, desquamation, and diffuse coagulation necrosis. Captopril treated rats, especially those given a high dose (more than 250 gm/l), revealed a marked reduction of the tubular and glomerular injuries. There was a statistically significant difference in the degree of renal injury among the experimental groups (p<0.05). The result of this study suggests that an administration of high dose captopril might prevent radiation-induced renal injury, especially in the early post-irradiation period.
- Histomorphologic Changes of Small Intestinal Mucosa after Irradiation in Rats.
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Chan Hwan Kim, Eun Sook Chang, Keon Young Kwon, Kwan Kyu Park, Ok Bae Kim
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Korean J Pathol. 1999;33(9):639-651.
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Abstract
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- Inadvertent application of ionizing radiation, a valuable tool in diagnostic radiology and radiotherapy, results in injury and death of adjacent normal cells, inducing gene mutations or even producing latent cancers. Captopril, an angiotensin I converting enzyme (ACE) inhibitor, has been reported to prevent the structural and functional changes in variable organs, such as lung and kidney, from radiation injury in different experimental animal models. An experiment was carried out to elucidate the radiation-induced histomorphologic changes of small intestine, especially jejunum, and to determine whether captopril can reduce or prevent the radiation-induced injuries in jejunum. Twenty-six healthy Sprague-Dawley rats were used.
Experimental group (n=24) was divided into two large groups: the first one (n=16) was treated with two different single dose (9 Gy, 17 Gy) irradiation only and was sacrificed at 12 hours and at 8 weeks following irradiation; the second one (n=8) received captopril 500 mg/l per oral continuously after same doses of irradiation and was sacrificed at 8 weeks. The control group (n=2) was maintained on a stock diet in a same period of experimental group and sacrificed coincidentally. On light and electron microscopy, the 9 Gy and 17 Gy 12 hours groups revealed frequent apoptosis and necrosis but extremely decreased mitotic figures of the crypt cells. However, the 9 Gy and 17 Gy 8 weeks groups and the combined irradiation with captopril groups showed extremely reduced apoptosis and necrosis with increased mitotic figures. There was good correlation between experimental groups in apoptotic count and mitotic count (p<0.05). In the 9 Gy and 17 Gy 12 hours groups, the mucosal surface was focally or diffusely fragmented and the villi were slightly to moderately distorted.
Collagen deposition was very mild and confined to the lower portion of the lamina propria.
The 9 Gy and 17 Gy 8 weeks groups showed more severe mucosal surface fragmentation even with foci of erosion, short and distorted villi, and more intense collagen deposition. In contrast, the combined irradiation with captopril groups revealed complete regeneration of the mucosal surface epithelium and absent collagen deposition. These findings suggest that the acute radiation injuries to small intestine occur principally in the mucosal crypt cells.
Captopril, the ACE inhibitor, might provide a useful intervention in the radiation injuries of intestinal mucosa.
- Morphologic Change of Proximal Convoluted Tubules in Radiation-Induced Renal Injury in Rats.
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Eun Sook Chang, Kun Young Kwon, Ok Bae Kim
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Korean J Pathol. 1999;33(8):555-569.
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Abstract
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- 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.
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