The development of effective methods and drugs to mitigate the nuclides absorption through intestinal mucus is an important area when nuclear accidents or terrorism happens.
PEG is commonly used in hospitals when colonoscopy is needed, due to its cathartic effect[16, 25]. DTPA is used as chelating agent, and chitosan has a protective effect on radiation . mPEGCS-DTPA was synthesized by chemical synthesis and cross-linking; it is a hydrophilic compound and cannot pass through the phospholipid bilayer of the cell membrane. mPEGCS-DTPA chelates heavy metal ion Sr, and can be quickly excreted from the body through the gastrointestinal tract, which can effectively reduce the absorption of heavy metal ions into the blood through the intestinal tract and prevent serious secondary damage to the body .
In this study, rats were orally gavaged with 89SrCl2 (48.8 × 104 Bq/mL, 1 mL ). At 48 h after oral gavage of 89SrCl2, the rats were sacrificed. The radioactivity count of the heart, liver, spleen, kidney and small intestine were close to the basal level, and a high amount of the radionuclide strontium was deposited in the bone tissue [4, 27, 5, 6].
The newly synthesized mPEGCS-DTPA was co-cultured with rat ICE-6 cells. CCK8 assay revealed that mPEGCS-DTPA was compatible with rat ICE-6 cells at different concentrations . The deposition of radionuclides in metacarpus and femur in mPEGCS-DTPA group was lower than that in NS group, indicating that mPEGCS-DTPA has certain chelating and promoting excretion ability. Previous studies have reported that the peak of strontium absorption into the blood through the digestive tract occurs at 60–120 min, which is consistent with our experimental results. The radioactivity count in blood at 24 h was close to the basal level, and we speculated that strontium was absorbed through the digestive tract mainly within 24 h after intake[5, 29]. The count of blood radioactivity in the mPEGCS-DTPA group and DTPA group was lower than that in the NS group at 2 and 8 h, and the lowest was observed in the mPEGCS-DTPA group at 8 h, which may be related to the massive excretion from the digestive tract. To find out the reasons for the differences in radioactivity count between different groups of bone tissue and blood, pathways of drug metabolism were also exposed. The results of fecal excretion revealed that the radioactive count of feces in the mPEGCS-DTPA group was higher than that in the other two groups on the first day after ingestion of 89SrCl2, and the total radioactive deposition in feces in the DTPA group was higher than that in the NS group on the second day after intake of strontium, which may be related to the slow excretion of DTPA chelating metal ions through the digestive tract [24, 15, 16]. However, no significant difference was observed in the chelation inhibition effect in the digestive tract compared with the traditional drug DTPA. Chitosan ingested through the digestive tract can be detected in the kidney in a short time[30, 10, 12]. In this study, the total radioactivity count in urine from the mPEGCS-DTPA group was significantly higher than that of the other two groups on the 1st and 2nd days after ingestion of 89SrCl2. We speculated that few 89SrCl2 was absorbed into the blood and chelated by mPEGCS-DTPA, and which might be excreted through urine [31, 30, 32].
The small intestinal mucosal injury caused by 89SrCl2 represents radiation injury; in the mPEGCS-DTPA group, this injury was less severe than that in the other two groups as observed by HE staining after ingestion of 89SrCl2 for 48 h. Moreover, chitosan has a certain radiation-protective effect on α and β rays, which may cause ionizing radiation damage . Combined with the previous research results of HE staining of rat small intestine, we speculate that the newly synthesized mPEGCS-DTPA has a certain radiation-protective effect on α and β rays, which may cause electric radiation damage to the digestive tract mucosa.
Thus, the results indicate that mPEGCS-DTPA exhibits good cytocompatibility, increases the excretion of the radionuclide strontium, and exerts radiation-protective effect against same in the digestive tract. Although the effect of the excretion of mPEGCS-DTPA still needs to be further explored and improved, it increases the oral dosage form of DTPA used in the digestive tract, has good ionizing radiation-protective effect, and can be used for clinical application.