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KMID : 0350519920450020685
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Journal of Catholic Medical College
1992 Volume.45 No. 2 p.685 ~ p.698
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Radioprotective Effect of Captopril on the Jejunal and Upper Gastrointestinal Mucosa, Liver, and Kidney in Irradiated Mice
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Abstract
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One of the factors limiting the radiation dose delivered to a tumor is the tolerance of normal tissue in the irradiated volume. The major hope improved local tumor control lies in the develpment of methods to enhance tumor-cell killing with
respect
to
normal tissues. Currently, there are three principal methods: high linear engergy transfer (LET) radiation, hyperbaric oxygen treatment, and radiation response modifiers to either sensitize tumors or protect normal tissues seletively.
Clinically, captopril, inhibitor of angiotensin-I converting enzyme, is used to treat systemic hypertension and congestive heart failure. These compounds appear to be potentially interesting radiation modifying agents and the ability of captopril
to
modify radiation damage appears to be neither species-nor tissue-specific.
In the present study, we determined whether captopril can reduce radiation change of the jejunum, esophagus, stomach, liver, and kidney in mice sacrificed on the 1st , 3rd , and 5th day after single dose of radiation with or without
administration
of
captopril in the feed. Mice were subjected to wholebody irradiation with 900 cGy and 1500 cGy, respectively, Captopril was administered in the feed at a regimen of 62.5mg/kg/day (captopril group I) and 125mg/kg/day (captopril group II)
continuously
7
days before irradiation and terminated at the end of each designed experiment. The jeiunal damage wa evaluated microscopically by crypt counts per ciroumference and histologic damage gradings. The damages to the esophagus, stomach, liver, and
kidney
were also studied histologically.
@ES The results were as follows:
@EN 1. Crypt number in normal group was 133.7*6.8/circumference. In both captopril I and II groups, crypt number and histolgic damages score were not significantly different from those in the normal group.
2. The 900 cGy and 1500 cGy radiation alone groups showed significantly lower crypt count and higher histolgic damage score compared with normal group(P<0.05).
3. The 900 cGy radiation plus captopril I and II group had significantly higher crypt count and lower histologic damage score on the 3rd day and lower histolgic damage score on the 5th day compared with the 900cGy radiation alone group(P<0.05).
4. The 1500 cGy radiation plus captopril I and II group had significantly higher crypt count and lower histologic damage score on the 3rd day than those of the 1500cGy radiation alone group (P<0.05). All mice of 1500cGy radiation group showed
intestinal radiation death within 5 days.
5. In the esophagus, stomach, liver, and kidney mild nonspecific inflammatory reactions such as edema, congestion, and hydropic degeneration were found under microscopic examination. There was no significant difference of damage between
radiation
alone
groups and radiation plus cptopril groups.
These results suggest that captopril provides protection form the radiation damage to the jejunal mucosa in mice.
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